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Barata PC, Zarrabi KK, Bex A, Grivas P, Hermann K, Hofman MS, Li R, Lopez-Beltran A, Padani AR, Powles T, Taplin ME, Loriot Y. Novel Methods to Assess Tumor Burden and Minimal Residual Disease in Genitourinary Cancers. Eur Urol 2025; 87:412-423. [PMID: 39638730 DOI: 10.1016/j.eururo.2024.11.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Revised: 10/23/2024] [Accepted: 11/06/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND AND OBJECTIVE Advances in molecular diagnostics have ushered in a new era for patients with prostate, renal, and urothelial cancers, with novel radiographic and molecular modalities for the assessment of disease burden and minimal residual disease (MRD). Conventional imaging has a limited threshold for disease detection and is often unable to discern clinically occult disease with varying risks of false-negative or false-positive findings depending on the disease state and type of imaging. METHODS We provide an overview of emerging radiographic and molecular tools in development within the genitourinary (GU) disease space. A literature review of contemporary basic, translational, and clinical research studies was performed, covering the timeframe of 1980-2024 through the MEDLINE (via PubMed) and Scopus databases. We highlight select examples of emerging technologies and biomarker-informed clinical trials, which aim to quantify disease at lower thresholds and have the potential for integrating MRD in clinical practice for GU patients. KEY FINDINGS AND LIMITATIONS The development of novel radiotracers, such as prostate-specific membrane antigen or carbonic anhydrase IX, is being evaluated in both clinical practice and trial setting, aiming to change the management of these tumors. Molecular tools including circulating tumor cells and byproducts such as plasma and urine cell-free circulating tumor DNA provide the opportunity for MRD detection. MRD capture on single-cell or cellular byproducts can serve as a conduit for genomic and transcriptomic analyses, providing insight into the molecular underpinnings and clonal evolution of disease. CONCLUSIONS AND CLINICAL IMPLICATIONS While the full potential for MRD applications has yet to be realized, we are witnessing the emergence of novel techniques aimed at MRD detection and the rapid development of elegantly designed studies implementing iterative detection of MRD as means to provide biological rationale and tailor therapeutic options in GU tumors.
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Affiliation(s)
- Pedro C Barata
- Division of Solid Tumor Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
| | - Kevin K Zarrabi
- Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
| | - Axel Bex
- The Royal Free London NHS Foundation Trust, London, UK; UCL Division of Surgery and Interventional Science, University College London, London, UK; Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - Petros Grivas
- Department of Medicine, Division of Hematology Oncology, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA, USA
| | - Ken Hermann
- Department of Nuclear Medicine, University of Duisburg-Essen, German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany
| | - Michael S Hofman
- Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
| | - Roger Li
- Department of GU Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Antonio Lopez-Beltran
- Department of Morphological Sciences, Unit of Anatomic Pathology, University of Cordoba Medical School, Cordoba, Spain
| | - Anwar R Padani
- Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, London, UK
| | - Thomas Powles
- Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St. Bartholomew's Hospital, London, UK
| | - Mary-Ellen Taplin
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Yohann Loriot
- Department of Cancer Medicine and INSERM U981, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France
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Patel P, Dreibe S, Attard G, Cole A, Diez P, Frew J, Guevara J, Levine D, McDonald F, Mullassery V, Murray J, Parker C, Palaniappan N, Pathmanathan A, Reid A, Suh YE, Syndikus I, Tirona A, Tran A, Tunariu N, van As NJ, Wylie J, Tree AC. Stereotactic Body Radiation Therapy for Oligoprogressive Disease in Androgen-Suppressed Prostate Cancer: Primary Endpoint Analysis of the TRAP Trial. Int J Radiat Oncol Biol Phys 2025:S0360-3016(25)00225-1. [PMID: 40068778 DOI: 10.1016/j.ijrobp.2025.02.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 02/12/2025] [Accepted: 02/27/2025] [Indexed: 04/09/2025]
Abstract
PURPOSE Optimal management of oligoprogressive prostate cancer while on androgen receptor pathway inhibitors (ARPIs) is not known. The TRAP trial tests the role of stereotactic body radiation therapy (SBRT) in this setting. The objective of this phase 2 prospective, nonrandomized, single-arm trial was to determine if local control of oligoprogressive disease with SBRT can delay further progression by >4 months, postponing time to next therapy. METHODS AND MATERIALS Men with castration-resistant prostate cancer with ≤2 oligoprogressive sites developing on treatment with an ARPI, after initial response to therapy, were recruited. All patients were treated to a dose of 30 Gy in 5 fractions (alternate days) or 36 Gy in 6 fractions weekly (prostate only). RESULTS Eighty-six men were recruited between October 2018 and February 2023. SBRT was delivered to 81 men. Mean age was 74 years. Most patients (67%) had 1 oligoprogressive disease lesion. Sites irradiated were bone (59%), lung (1%), lymph node (32%), and prostate (7%). Median follow-up was 22.9 months at the time of analysis. Fifty-five (68%) patients had progressed, 33 (41%) of patients progressed within 6 months of radiation therapy. Median progression-free survival (PFS) was 6.4 months (95% CI, 5.9-11.4). An estimated 39% (95% CI, 29-49) of patients have a prolonged PFS of > 12 months. Thirty-three (41%) of patients had started new treatment or died. Median time to either next treatment or death was 27.0 months (95% CI, 14.9-29.6). Median overall survival was 27.2 months (95% CI, 24.7-36.6). Four deaths occurred within 6 months of SBRT; none were related to radiation therapy treatment. CONCLUSIONS The TRAP trial has demonstrated a median PFS of 6.4 months after SBRT for oligoprogression of prostate cancer, meeting the primary endpoint. Further analysis of biomarker panel including circulating DNA and whole-body magnetic resonance imaging will promote better patient selection.
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Affiliation(s)
- Priyanka Patel
- The Royal Marsden NHS Foundation Trust, London, United Kingdom.
| | - Sabine Dreibe
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Gerhardt Attard
- University College London Cancer Institute, London, United Kingdom; University College London Hospital, London, United Kingdom
| | - Aidan Cole
- Queen's University Belfast, Lisburn Road Belfast, United Kingdom
| | - Patricia Diez
- Radiotherapy Physics, National Radiotherapy Trials Quality Assurance Group (RTTQA), Mount Vernon Cancer Centre, Northwood, United Kingdom
| | - John Frew
- Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle-Upon-Tyne, United Kingdom
| | - Jeane Guevara
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Daniel Levine
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Fiona McDonald
- The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom
| | | | - Julia Murray
- The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom
| | - Chris Parker
- The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom
| | | | - Angela Pathmanathan
- The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom
| | - Alison Reid
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Yae-Eun Suh
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Isabel Syndikus
- The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, United Kingdom
| | - Angelie Tirona
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Amina Tran
- The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Nina Tunariu
- The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom
| | - Nicholas J van As
- The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom
| | - James Wylie
- The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Alison C Tree
- The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom
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Paccini M, Paschina G, De Beni S, Stefanov A, Kolev V, Patanè G. US & MR/CT Image Fusion with Markerless Skin Registration: A Proof of Concept. JOURNAL OF IMAGING INFORMATICS IN MEDICINE 2025; 38:615-628. [PMID: 39020154 PMCID: PMC11810866 DOI: 10.1007/s10278-024-01176-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 05/18/2024] [Accepted: 05/31/2024] [Indexed: 07/19/2024]
Abstract
This paper presents an innovative automatic fusion imaging system that combines 3D CT/MR images with real-time ultrasound acquisition. The system eliminates the need for external physical markers and complex training, making image fusion feasible for physicians with different experience levels. The integrated system involves a portable 3D camera for patient-specific surface acquisition, an electromagnetic tracking system, and US components. The fusion algorithm comprises two main parts: skin segmentation and rigid co-registration, both integrated into the US machine. The co-registration aligns the surface extracted from CT/MR images with the 3D surface acquired by the camera, facilitating rapid and effective fusion. Experimental tests in different settings, validate the system's accuracy, computational efficiency, noise robustness, and operator independence.
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Affiliation(s)
| | | | | | | | - Velizar Kolev
- MedCom GmbH, Dolivostr., 11, Darmstadt, 64293, Germany
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Alerasool P, Zhou S, Miller E, Anker J, Tsao B, Kyprianou N, Tsao CK. A Personalized Approach for Oligometastatic Prostate Cancer: Current Understanding and Future Directions. Cancers (Basel) 2025; 17:147. [PMID: 39796774 PMCID: PMC11720581 DOI: 10.3390/cancers17010147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/24/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
Oligometastatic prostate cancer (OMPC) represents an intermediate state in the progression from localized disease to widespread metastasis when the radiographically significant sites are limited in number and location. With no clear consensus on a definition, its diagnostic significance and associated optimal therapeutic approach remain controversial, posing a significant challenge for clinicians. The current standard of care for metastatic disease is to start systemic therapy; however, active surveillance and targeted radiotherapy have become attractive options to mitigate the long-term effects of androgen deprivation therapy (ADT). Furthermore, evolving biomarker methodologies may further define optimal treatment selection. In this review, we summarize the current understanding that guides the treatment of OMPC, with a focus on how host response can be an important contributing factor. Evolving scientific understanding and clinical development will continue to shape the landscape of treatment strategies for this distinct disease state.
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Affiliation(s)
- Parissa Alerasool
- Department of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA (C.-K.T.)
- Department of Medicine, Montefiore Medical Center Albert Einstein College of Medicine, Bronx, NY 10467, USA
| | - Susu Zhou
- Department of Medicine, Icahn School of Medicine at Mount Sinai (Morningside/West), New York, NY 10025, USA
| | - Eric Miller
- Department of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA (C.-K.T.)
| | - Jonathan Anker
- Department of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA (C.-K.T.)
| | - Brandon Tsao
- Department of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA (C.-K.T.)
| | - Natasha Kyprianou
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Che-Kai Tsao
- Department of Hematology-Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA (C.-K.T.)
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Liu WQ, Xue YT, Huang XY, Lin B, Li XD, Ke ZB, Chen DN, Chen JY, Wei Y, Zheng QS, Xue XY, Xu N. Development and Validation of an MRI-Based Radiomics Nomogram to Predict the Prognosis of De Novo Oligometastatic Prostate Cancer Patients. Cancer Med 2024; 13:e70481. [PMID: 39704412 DOI: 10.1002/cam4.70481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 11/16/2024] [Accepted: 11/28/2024] [Indexed: 12/21/2024] Open
Abstract
OBJECTIVE We aimed to develop and validate a nomogram based on MRI radiomics to predict overall survival (OS) for patients with de novo oligometastatic prostate cancer (PCa). METHODS A total of 165 patients with de novo oligometastatic PCa were included in the study (training cohort, n = 115; validating cohort, n = 50). Among them, MRI scans were conducted and T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences were collected for radiomics features along with their clinicopathological features. Radiological features were extracted from T2WI and ADC sequences for prostate tumors. Univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) combined with 10-fold cross-validation were used to select the optimal features on each sequence. Then, a weighted radiomics score (Rad-score) was generated and independent risk factors were obtained from univariate and multivariate Cox regressions to build the nomogram. Model performance was assessed using receiver operating characteristic (ROC) curves, calibration, and decision curve analysis (DCA). RESULTS Eastern Cooperative Oncology Group (ECOG) score, absolute neutrophil count (ANC) and Rad-score were included in the nomogram as independent risk factors for OS in de novo oligometastatic PCa patients. We found that the areas under the curves (AUCs) in the training cohort were 0.734, 0.851, and 0.773 for predicting OS at 1, 2, and 3 years, respectively. In the validating cohort, the AUCs were 0.703, 0.799, and 0.833 for predicting OS at 1, 2, and 3 years, respectively. Furthermore, the clinical relevance of the predictive nomogram was confirmed through the analysis of DCA and calibration curve analysis. CONCLUSION The MRI-based nomogram incorporating Rad-score and clinical data was developed to guide the OS assessment of oligometastatic PCa. This helps in understanding the prognosis and improves the shared decision-making process.
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Affiliation(s)
- Wen-Qi Liu
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yu-Ting Xue
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xu-Yun Huang
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Bin Lin
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xiao-Dong Li
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Zhi-Bin Ke
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Dong-Ning Chen
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Jia-Yin Chen
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yong Wei
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Qing-Shui Zheng
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Xue-Yi Xue
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Ning Xu
- Department of Urology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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Li X, Sun Y, Tang L, Li Y, Yang X. Treatment of metastatic breast cancer by stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS). Discov Oncol 2024; 15:733. [PMID: 39616564 PMCID: PMC11609137 DOI: 10.1007/s12672-024-01595-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 11/15/2024] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND AND PURPOSE The role of local ablative radiotherapy (stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS)) in the management of metastatic breast cancer (mBC) patients remains unclear. This study aimed to assess the efficacy of SBRT/SRS in oligometastatic and oligoprogressive breast cancer patients. METHODS Totally 80 mBC patients with oligometastatic disease (OMD) and 80 with oligoprogressive disease (OPD) to ≤5 metastatic lesions were retrospectively analyzed. The endpoint was overall survival and progression-free survival, and univariate and multivariate analyses were performed for survival analysis. RESULTS Totally 160 mBC cases (80 OMD and 80 OPD cases) were analyzed, with a total of 291 treated metastases. In the study of OMD, we analyzed 30 cases with oligo-recurrence and 50 cases with sync-oligometastases. The median follow-up time was 46 months, and 1-, 2-, and 3-year OS rates for all patients were 89.8%, 77.6%, and 67.3%, respectively, and the 1-, 2-, and 3-year PFS rates were 71.4%, 44.9%, and 34.7% respectively. In multivariate analysis (MVA), treatment for oligometastases and non-triple-negative status predicted favorable OS. In patients with oligometastases, median OS was 58 months, and 1-, 2-, and 3-year OS rates were 100%, 91.7%, and 83.3%, respectively; median OS in patients with oligoprogression was 35 months, and 1-, 2-, and 3-year OS rates were 80%, 64%, and 52%, respectively. In mBC cases with limited brain metastases administered SRS, poor OS was detected in patient age under 45 years (P = 0.041), triple-negative cases (P = 0.025), and those with OPD (P = 0.022). In OMD, a significant improvement in PFS was observed in the oligo-recurrence group compared to the sync-oligometastases group (P = 0.013). CONCLUSION Patients administered local ablative radiotherapy (SBRT/SRS) for oligometastases have better overall survival than those treated for oligoprogression. SBRT/SRS may be beneficial for young and non-triple-negative mBC cases. The presence of oligo-recurrence can predict a favorable prognosis of oligometastases in patients with mBC treated with SBRT/SRS.
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Affiliation(s)
- Xiaomin Li
- Division of Breast Surgery, Department of General Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, China
- Breast Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yu Sun
- Radiotherapy Physics & Technology Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Liang Tang
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yan Li
- Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
- Department of Lung Cancer Center, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, China.
| | - Xiaoqin Yang
- Division of Breast Surgery, Department of General Surgery, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, China.
- Breast Center, West China Hospital, Sichuan University, Chengdu, China.
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Aman A, Akram A, Akram B, Husnain A, Akram A, Akram S, Ahmad E, Nadeem A. Salvage Stereotactic Radiotherapy for Nodal Oligo-Recurrent Prostate Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Clin Genitourin Cancer 2024; 22:102239. [PMID: 39561634 DOI: 10.1016/j.clgc.2024.102239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 09/21/2024] [Accepted: 09/23/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Prostate cancer has a high frequency of relapse, and the relapse is usually associated with a nodal recurrence pattern spreading predominantly to fewer pelvic or extra-pelvic lymph nodes. This meta-analysis sought to determine the safety and survival outcomes of salvage body stereotactic radiotherapy (SBRT) in oligo-recurrent nodal prostate cancer patients. METHODS We searched the Cochrane Central Register of Controlled Trials, PubMed, ClinicalTrials.gov, and Google Scholar to retrieve all the relevant randomized controlled trials (RCTs) from inception to May 2024. Dichotomous outcomes were pooled using risk ratios (RR) with a 95% confidence interval (CI), whereas survival outcomes were reported using hazard ratios (HR) with a 95% CI. RESULTS Three RCTs with a total of 312 patients (median age range of >18-79) were included. Of 312 patients, 135 received SBRT with medical therapy, while 122 underwent either observation, medical therapy, or elective nodal radiotherapy. SBRT significantly increased the biochemical recurrence-free survival (HR: 0.45; 95% CI, 0.28-0.73) with minimal inter-study heterogeneity (I2 = 0%). SBRT did not affect the grade 2 genitourinary (GU) toxicity levels (Common Terminology Criteria for Adverse Events [CTCAE] v4.0) (RR: 0.74; 95% CI, 0.32-1.70; (I2 = 0%) nor the grade 2 gastrointestinal (GI) toxicity levels (CTCAE v4.0) (RR: 1.05; 95% CI, 0.26-4.31; I2 = 0%). SBRT was not associated with any significant change in the grade 1 toxicity levels (CTCAE v4.0) (RR, 1.08; 95% CI, 0.62-1.89) with moderate heterogeneity (I2 = 63%). CONCLUSION SBRT improves biochemical recurrence-free survival in patients with oligo-recurrent prostate cancer without increasing grade 1 and grade 2 GU/GI toxicity levels.
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Affiliation(s)
- Ayesha Aman
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Arfa Akram
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Bisma Akram
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Ali Husnain
- Department of Radiology, Section of Interventional Radiology, Northwestern University, Chicago, IL
| | - Aleena Akram
- Department of Medicine, Shalamar Medical and Dental College, Lahore, Pakistan
| | - Sania Akram
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
| | - Eeman Ahmad
- Department of Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan
| | - Arsalan Nadeem
- Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan.
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Colciago RR, Chissotti C, Ferrario F, Belmonte M, Purrello G, Faccenda V, Panizza D, Canova S, Passarella G, Cortinovis DL, Arcangeli S. Time to Next Treatment Following Sub-Ablative Progression Directed Radiation Therapy for Oligoprogressive Non-Small-Cell Lung Cancer. Curr Oncol 2024; 31:6840-6852. [PMID: 39590136 PMCID: PMC11592685 DOI: 10.3390/curroncol31110505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024] Open
Abstract
We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12-60) in five fractions (1-10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4-151.2). After a median follow-up of 11 months (2-50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1-47) with a one-year Kaplan-Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No >grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT.
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Affiliation(s)
- Riccardo Ray Colciago
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
| | - Chiara Chissotti
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
- Radiation Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (V.F.); (D.P.)
| | - Federica Ferrario
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
- Radiation Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (V.F.); (D.P.)
| | - Maria Belmonte
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
- Radiation Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (V.F.); (D.P.)
| | - Giorgio Purrello
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
- Radiation Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (V.F.); (D.P.)
| | - Valeria Faccenda
- Radiation Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (V.F.); (D.P.)
- Medical Physics Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Denis Panizza
- Radiation Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (V.F.); (D.P.)
- Medical Physics Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Stefania Canova
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy;
| | - Gaia Passarella
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy;
| | - Diego Luigi Cortinovis
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
- Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy;
| | - Stefano Arcangeli
- Medicine and Surgery Department, University of Milan Bicocca, 20126 Milano, Italy; (R.R.C.); (C.C.); (M.B.); (G.P.); (G.P.); (D.L.C.); (S.A.)
- Radiation Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (V.F.); (D.P.)
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9
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Patel PH, Dreibe S, Reid A, Parker C, Murray J, Pathmanathan A, Tirona A, Guevara J, Suh YE, Frew J, Palaniappan N, Syndikus I, Attard G, Tunariu N, Tree AC. Stereotactic Body Radiotherapy for Oligoprogression in Castration-Resistant Prostate Cancer: Early Toxicity Analysis of the TRAP Trial. Clin Oncol (R Coll Radiol) 2024; 36:585-592. [PMID: 39004535 DOI: 10.1016/j.clon.2024.06.047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 06/10/2024] [Accepted: 06/13/2024] [Indexed: 07/16/2024]
Abstract
AIMS To assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA). MATERIAL AND METHODS This phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression. All patients received SBRT to the OPD site(s) and continued the current ARTA. Patients received 30 Gy in 5 fractions (alternate days) to the OPD site. The primary endpoint of the trial is to assess if SBRT to OPD sites results in progression free survival of >6 months. The primary endpoint for this toxicity analysis is the rate of grade 3 or higher adverse events at any timepoint up to 6 months after SBRT. Secondary endpoints included comparing pre- and post-SBRT patient-related outcomes reported using visual analogue scale scores and EQ-5D health questionnaire. RESULTS Forty enrolled patients had at least 6 months of follow-up at the time of analysis. Grade 3 or higher toxicity from any cause recorded using common terminology criteria for adverse events and radiation therapy oncology group was found in 8/40 (20%) of patients, but only 1/40 (2.5%) was deemed possibly related to SBRT. There was no significant difference in mean EQ5D visual analogue scale score from baseline to each timepoint after SBRT (p = 0.449). CONCLUSION In this prospective phase II clinical trial for OPD whilst on ARTA in the CRPC setting, we report low grade ≥ 3 toxicity after SBRT. There is no discernible change in patient-reported quality of life due to SBRT treatment. The final results of progression-free survival and toxicity of SBRT treatment will be reported once further follow-up is complete.
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Affiliation(s)
- P H Patel
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK.
| | - S Dreibe
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK
| | - A Reid
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK
| | - C Parker
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK; The Institute of Cancer Research, London, SM2 5NG, UK
| | - J Murray
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK; The Institute of Cancer Research, London, SM2 5NG, UK
| | - A Pathmanathan
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK
| | - A Tirona
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK
| | - J Guevara
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK
| | - Y-E Suh
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK
| | - J Frew
- Newcastle Upon Tyne Hospital NHS Foundation Trust, Newcastle-Upon-Tyne, NE7 7DN, UK
| | | | - I Syndikus
- The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, CH63 4JY, UK
| | - G Attard
- University College London Cancer Institue, London, NW1 2BU, UK; University College London Hospital, London, NW1 2BU, UK
| | - N Tunariu
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK
| | - A C Tree
- The Royal Marsden NHS Foundation Trust, London, SM2 5PT, UK; The Institute of Cancer Research, London, SM2 5NG, UK
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10
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Sheikh GT, Trapp C, Schmidt-Hegemann NS, Buchner A, Stief CG, Unterrainer M, Kunz WG, Cyran CC, Grawe F, Delker A, Zacherl MJ, Holzgreve A, Unterrainer LM, Brendel M, Belka C, Li M, Rogowski P. PSMA-PET/CT response after metastasis-directed radiotherapy of bone oligometastases in prostate cancer. EJNMMI REPORTS 2024; 8:25. [PMID: 39155339 PMCID: PMC11330950 DOI: 10.1186/s41824-024-00212-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 05/14/2024] [Indexed: 08/20/2024]
Abstract
OBJECTIVE Bone metastases are very common in advanced prostate cancer and can sensitively be detected utilizing PSMA-PET/CT. Therefore, our goal was to evaluate the suitability of PSMA-PET/CT-guided metastasis-directed external beam radiotherapy (MDT) as treatment option for patients with biochemical recurrence and oligometastatic bone lesions. MATERIALS & METHODS We retrospectively examined 32 prostate cancer patients with biochemical recurrence and PSMA-positive oligometastatic disease limited to the bone (n = 1-3). A total of 49 bone lesions were treated with MDT. All patients received a post-radiotherapy PSMA-PET/CT-Scan. Changes in SUVmax, PSMA-positive tumor volume per lesion and PSA, as well as the correlation between the PET/CT-interval and SUVmax response were calculated. RESULTS MDT lead to a SUVmax decrease in 46/49 (94%) of the lesions. The median relative decline of SUVmax was 60.4%, respectively. Based on PSMA-positive lesion volume with a SUV cut-off of 4, 46/49 (94%) of lesions showed complete response, two (4%) partial response and one lesion (2%) was stable on PSMA-PET/CT after MDT. Most of the treated patients (56.3%) showed an initial PSA decline at three months and a PSA nadir of median 0.14 ng/ml after a median time of 3.6 months after MDT. The median relative PSA change at three months after MDT was 3.9%. CONCLUSION MDT is a very effective treatment modality for prostate cancer bone oligometastases and lesion response to MDT can be assessed using the (semi-)quantitative parameters SUVmax and PSMA-positive lesion volume with established SUV cut-offs.
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Affiliation(s)
- Gabriel T Sheikh
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
| | - Christian Trapp
- Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany
| | | | - Alexander Buchner
- Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Christian G Stief
- Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Marcus Unterrainer
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Wolfgang G Kunz
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Clemens C Cyran
- Department of Radiology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Freba Grawe
- German Cancer Research Center (DKFZ), Hector Cancer Institute at the University Medical Center Mannheim, Heidelberg, Germany
- Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg University, Mannheim, Germany
| | - Astrid Delker
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Mathias J Zacherl
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Adrien Holzgreve
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Lena M Unterrainer
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
- Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, USA
| | - Matthias Brendel
- Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Claus Belka
- Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany
- German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Minglun Li
- Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany
| | - Paul Rogowski
- Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany
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11
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Yoo GS, Park S, Rim CH, Cho WK, Chang AR, Kim YS, Ahn YC, Chie EK. Radiation Oncologists' Perspectives on Oligometastatic Prostate Cancer: A Survey from Korean Oligometastasis Working Group. Curr Oncol 2024; 31:3239-3251. [PMID: 38920729 PMCID: PMC11203304 DOI: 10.3390/curroncol31060245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 05/25/2024] [Accepted: 05/31/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Interest in the oligometastatic prostate cancer (OMPC) is increasing, and various clinical studies have reported the benefits of metastasis-directed radiation therapy (MDRT) in OMPC. However, the recognition regarding the adopted definitions, methodologies of assessment, and therapeutic approaches is diverse among radiation oncologists. This study aims to evaluate the level of agreement for issues in OMPC among radiation oncologists. METHODS We generated 15 key questions (KQs) for OMPC relevant to definition, diagnosis, local therapies, and endpoints. Additionally, three clinical scenarios representing synchronous metastatic prostate cancer (mPC) (case 1), metachronous mPC with visceral metastasis (case 2), and metachronous mPC with castration-resistance and history of polymetastasis (case 3) were developed. The 15 KQs were adapted according to each scenario and transformed into 23 questions with 6-9 per scenario. The survey was distributed to 80 radiation oncologists throughout the Republic of Korea. Answer options with 0.0-29.9%, 30-49.9%, 50-69.9%, 70-79.9%, 80-89.9%, and 90-100% agreements were considered as no, minimal, weak, moderate, strong, and near perfect agreement, respectively. RESULTS Forty-five candidates voluntarily participated in this study. Among 23 questions, near perfect (n = 4), strong (n = 3), or moderate (n = 2) agreements were shown in nine. For the case recognized as OMPC with agreements of 93% (case 1), near perfect agreements on the application of definitive radiation therapy (RT) for whole metastatic lesions were achieved. While ≥70% agreements regarding optimal dose-fractionation for metastasis-directed RT (MDRT) has not been achieved, stereotactic body RT (SBRT) is favored by clinicians with higher clinical volume. CONCLUSION For the case recognized as OMPC, near perfect agreement for the application of definitive RT for whole metastatic lesions was reached. SBRT was more favored as a MDRT by clinicians with a higher clinical volume.
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Affiliation(s)
- Gyu Sang Yoo
- Department of Radiation Oncology, Chungbuk National University Hospital, Cheongju 28644, Republic of Korea
| | - Sunmin Park
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Seoul 15355, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Ansan Hospital, Korea University Medical College, Seoul 15355, Republic of Korea
| | - Won Kyung Cho
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Ah Ram Chang
- Department of Radiation Oncology/Cyberknife Center, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul 04401, Republic of Korea
| | - Young Seok Kim
- Department of Radiation Oncology, Asan Medical Center, Ulsan University School of Medicine, Seoul 05505, Republic of Korea
| | - Yong Chan Ahn
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
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12
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Mahmoud AM, Moustafa A, Day C, Ahmed ME, Zeina W, Marzouk UM, Basourakos S, Haloi R, Mahon M, Muniz M, Childs DS, Orme JJ, Riaz IB, Kendi AT, Stish BJ, Davis BJ, Kwon ED, Andrews JR. Prostate Cancer Lung Metastasis: Clinical Insights and Therapeutic Strategies. Cancers (Basel) 2024; 16:2080. [PMID: 38893199 PMCID: PMC11171228 DOI: 10.3390/cancers16112080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/23/2024] [Accepted: 05/28/2024] [Indexed: 06/21/2024] Open
Abstract
Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.
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Affiliation(s)
- Ahmed M. Mahmoud
- Department of Urology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.M.)
| | - Amr Moustafa
- Department of Internal Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11201, USA
| | - Carter Day
- Department of Urology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.M.)
| | - Mohamed E. Ahmed
- Department of Urology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.M.)
| | - Wael Zeina
- Department of Urology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.M.)
| | - Usama M. Marzouk
- Department of Internal Medicine, Ain Shams University, Cairo 11566, Egypt
| | | | - Rimki Haloi
- Department of Urology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.M.)
| | - Mindie Mahon
- Department of Urology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.M.)
| | - Miguel Muniz
- Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Daniel S. Childs
- Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Jacob J. Orme
- Department of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Irbaz Bin Riaz
- Department of Medical Oncology, Mayo Clinic, Scottsdale, AZ 85259, USA
| | - A. Tuba Kendi
- Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, MN 55905, USA;
| | - Bradley J. Stish
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Brian J. Davis
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | - Eugene D. Kwon
- Department of Urology, Mayo Clinic, Rochester, MN 55905, USA; (A.M.M.)
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13
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Tsai CJ, Yang JT, Shaverdian N, Patel J, Shepherd AF, Eng J, Guttmann D, Yeh R, Gelblum DY, Namakydoust A, Preeshagul I, Modi S, Seidman A, Traina T, Drullinsky P, Flynn J, Zhang Z, Rimner A, Gillespie EF, Gomez DR, Lee NY, Berger M, Robson ME, Reis-Filho JS, Riaz N, Rudin CM, Powell SN. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet 2024; 403:171-182. [PMID: 38104577 PMCID: PMC10880046 DOI: 10.1016/s0140-6736(23)01857-3] [Citation(s) in RCA: 93] [Impact Index Per Article: 93.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 07/27/2023] [Accepted: 08/31/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes. METHODS We did a phase 2, open-label, randomised controlled trial of SBRT in patients with oligoprogressive metastatic breast cancer or non-small-cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as five or less progressive lesions on PET-CT or CT. Patients aged 18 years or older were enrolled from a tertiary cancer centre in New York, NY, USA, and six affiliated regional centres in the states of New York and New Jersey, with a 1:1 randomisation between standard of care (standard-of-care group) and SBRT plus standard of care (SBRT group). Randomisation was done with a computer-based algorithm with stratification by number of progressive sites of metastasis, receptor or driver genetic alteration status, primary site, and type of systemic therapy previously received. Patients and investigators were not masked to treatment allocation. The primary endpoint was progression-free survival, measured up to 12 months. We did a prespecified subgroup analysis of the primary endpoint by disease site. All analyses were done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03808662, and is complete. FINDINGS From Jan 1, 2019, to July 31, 2021, 106 patients were randomly assigned to standard of care (n=51; 23 patients with breast cancer and 28 patients with NSCLC) or SBRT plus standard of care (n=55; 24 patients with breast cancer and 31 patients with NSCLC). 16 (34%) of 47 patients with breast cancer had triple-negative disease, and 51 (86%) of 59 patients with NSCLC had no actionable driver mutation. The study was closed to accrual before reaching the targeted sample size, after the primary efficacy endpoint was met during a preplanned interim analysis. The median follow-up was 11·6 months for patients in the standard-of-care group and 12·1 months for patients in the SBRT group. The median progression-free survival was 3·2 months (95% CI 2·0-4·5) for patients in the standard-of-care group versus 7·2 months (4·5-10·0) for patients in the SBRT group (hazard ratio [HR] 0·53, 95% CI 0·35-0·81; p=0·0035). The median progression-free survival was higher for patients with NSCLC in the SBRT group than for those with NSCLC in the standard-of-care group (10·0 months [7·2-not reached] vs 2·2 months [95% CI 2·0-4·5]; HR 0·41, 95% CI 0·22-0·75; p=0·0039), but no difference was found for patients with breast cancer (4·4 months [2·5-8·7] vs 4·2 months [1·8-5·5]; 0·78, 0·43-1·43; p=0·43). Grade 2 or worse adverse events occurred in 21 (41%) patients in the standard-of-care group and 34 (62%) patients in the SBRT group. Nine (16%) patients in the SBRT group had grade 2 or worse toxicities related to SBRT, including gastrointestinal reflux disease, pain exacerbation, radiation pneumonitis, brachial plexopathy, and low blood counts. INTERPRETATION The trial showed that progression-free survival was increased in the SBRT plus standard-of-care group compared with standard of care only. Oligoprogression in patients with metastatic NSCLC could be effectively treated with SBRT plus standard of care, leading to more than a four-times increase in progression-free survival compared with standard of care only. By contrast, no benefit was observed in patients with oligoprogressive breast cancer. Further studies to validate these findings and understand the differential benefits are warranted. FUNDING National Cancer Institute.
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Affiliation(s)
- Chiaojung Jillian Tsai
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
| | - Jonathan T Yang
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Narek Shaverdian
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Juber Patel
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Annemarie F Shepherd
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Juliana Eng
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David Guttmann
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Randy Yeh
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Daphna Y Gelblum
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Azadeh Namakydoust
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Isabel Preeshagul
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Shanu Modi
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andrew Seidman
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Tiffany Traina
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Pamela Drullinsky
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jessica Flynn
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Zhigang Zhang
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Andreas Rimner
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Erin F Gillespie
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Daniel R Gomez
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nancy Y Lee
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael Berger
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mark E Robson
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jorge S Reis-Filho
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nadeem Riaz
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Charles M Rudin
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Simon N Powell
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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14
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Gomez Rivas J, Nicoletti R, Ibáñez L, Steinbeisser C, de Meulder B, Golozar A, Axelsson SE, Snijder R, Bjartell A, Cornford P, Van Hemelrijck M, Beyer K, Willemse PP, Murtola T, Roobol MJ, Moreno-Sierra J, Campi R, Gacci M, Mottet N, Merseburger A, Ndow J. Research protocol to identify progression and death amongst patients with metastatic hormone-sensitive prostate cancer treated with available treatments: PIONEER IMI's "big data for better outcomes" program. Int J Surg Protoc 2023; 27:122-129. [PMID: 38046899 PMCID: PMC10688536 DOI: 10.1097/sp9.0000000000000009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 06/24/2023] [Indexed: 12/05/2023] Open
Abstract
Androgen deprivation therapy-based with or without first-generation anti-androgens, was the standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) for decades. However, the development of docetaxel chemotherapy and new androgen receptor-targeted agents, abiraterone acetate and prednisolone, apalutamide , enzalutamide and darolutamide (in combination with docetaxel chemotherapy) has proven that combination of treatments is more effective. Recently, intensification therapy, so-called "triplets", have emerged in the armamentarium of mHSPC treatment. Metastatic disease is a clinical state that remains poorly understood. The optimal diagnostic and management of patients with mHSPC are changing thanks to the development of new imaging techniques and therapies. The primary objective of this study is to develop and validate a predictive model for the occurrence of symptomatic progression, initiation of new treatments and death amongst patients with mHSPC treated with one of the approved treatment plans, on characteristics present at admission.
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Affiliation(s)
- Juan Gomez Rivas
- Department of Urology, Hospital Clínico San Carlos, Madrid, Spain
| | - Rossella Nicoletti
- Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy
| | - Laura Ibáñez
- Department of Urology, Hospital Clínico San Carlos, Madrid, Spain
| | | | - Bertrand de Meulder
- European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Lyon
| | - Asieh Golozar
- Regeneron Pharmaceuticals, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA
| | | | | | | | | | | | | | - Peter-Paul Willemse
- Department of Urology, Cancer Center University Medical Center Utrecht, Utrecht
| | - Teemu Murtola
- Department of Urology, Tampere University Hospital, Tampere, Finland; Department of Surgery, Seinäjoki Central Hospital, Seinäjoki, Finland
| | | | | | - Riccardo Campi
- Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy
| | - Mauro Gacci
- Unit of Urological Robotic Surgery and Renal Transplantation, University of Florence, Careggi Hospital, Florence, Italy
| | - Nicolas Mottet
- Department of Urology, Hospitalier Universitaire de Saint-Étienne, Saint-Étienne, France
| | - Axel Merseburger
- University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - James Ndow
- Department of Urology, University of Aberdeen, Aberdeen, Scotland
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Ciérvide R, Hernando O, López M, Montero Á, Zucca D, Sánchez E, Álvarez B, García-Aranda M, Chen Zhao X, Valero J, Alonso R, Martí J, de la Casa MÁ, Alonso L, García J, Garcia de Acilu P, Prado A, Fernandez Leton P, Rubio C. Stereotactic body radiation therapy (SBRT) for spinal metastases: 12 years of a single center experience. Clin Transl Oncol 2023; 25:3395-3404. [PMID: 37058207 DOI: 10.1007/s12094-023-03188-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 04/03/2023] [Indexed: 04/15/2023]
Abstract
OBJECTIVE To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. MATERIALS AND METHODS Patients with spine metastases treated with SBRT (1 fraction/18 Gy or 5 fractions/7 Gy) during the last 12 years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. RESULTS From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18 Gy (75%) or 5 fractions/7 Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2 months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3 years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). CONCLUSIONS According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.
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Affiliation(s)
- Raquel Ciérvide
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain.
| | - Ovidio Hernando
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Mercedes López
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Ángel Montero
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Daniel Zucca
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Emilio Sánchez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Beatriz Álvarez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Mariola García-Aranda
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Xin Chen Zhao
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Jeannette Valero
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Rosa Alonso
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Jaime Martí
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Miguel Ángel de la Casa
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Leire Alonso
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Juan García
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Paz Garcia de Acilu
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Alejandro Prado
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Pedro Fernandez Leton
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Carmen Rubio
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid, Spain
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Grkovski M, O'Donoghue JA, Imber BS, Andl G, Tu C, Lafontaine D, Schwartz J, Thor M, Zelefsky MJ, Humm JL, Bodei L. Lesion Dosimetry for [ 177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer. J Nucl Med 2023; 64:1779-1787. [PMID: 37652541 PMCID: PMC10626375 DOI: 10.2967/jnumed.123.265763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 07/11/2023] [Indexed: 09/02/2023] Open
Abstract
A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [177Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax). After a second cycle of [177Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4-1.7 cm3 The median lesion-absorbed dose (AD) from the first cycle of [177Lu]Lu-PSMA-617 RPT (ADRPT) was 27.7 Gy (range, 8.3-58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1-7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7-28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax (P = 0.005), 0.74 (P = 0.046) between the baseline PET SUVmax and the lesion ADRPT, and -0.81 (P = 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124-219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was -0.88 (P = 0.007). Two cycles of [177Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues.
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Affiliation(s)
- Milan Grkovski
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York;
| | - Joseph A O'Donoghue
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Brandon S Imber
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - George Andl
- Varian Medical Systems Inc., Palo Alto, California; and
| | - Cheng Tu
- Varian Medical Systems Inc., Palo Alto, California; and
| | - Daniel Lafontaine
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jazmin Schwartz
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Maria Thor
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael J Zelefsky
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - John L Humm
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Lisa Bodei
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
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Landen L, Devos G, Joniau S, Albersen M. Penile metastasis in prostate cancer patients: Two case reports, surgical excision technique, and literature review. Curr Urol 2023; 17:165-172. [PMID: 37448616 PMCID: PMC10337815 DOI: 10.1097/cu9.0000000000000093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 08/27/2021] [Indexed: 11/25/2022] Open
Abstract
Two cases of penile metastasis from primary prostate cancer in a single center are presented, along with a literature review and description of the excision technique. Despite its rich vascularization, penile metastasis is rare, with 72 new cases from September 2006 to March 2021. There is a wide variety of diagnoses, treatments, and prognoses for penile metastatic lesions. Ga-68 prostatespecific membrane antigen positron emission tomography/computed tomography is the most sensitive imaging tool for detecting metastasis from primary prostate cancer. Magnetic resonance imaging of the penis is the most reliable technique for differentiating penile lesions. Histological diagnosis is mostly performed using fine-needle biopsy aspiration. Metastasis-directed treatment is not considered to contribute to prolonged survival. Local treatment is feasible and can be offered to symptomatic patients. Owing to a heterogeneous group, defining overall survival is difficult. Survival until 46months after detecting penile metastases is described.
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Affiliation(s)
- Lucas Landen
- Department of Urology, University Hospitals Leuven, Leuven, Belgium
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Zapatero A, Conde Moreno AJ, Barrado Los Arcos M, Aldave D. Node Oligorecurrence in Prostate Cancer: A Challenge. Cancers (Basel) 2023; 15:4159. [PMID: 37627187 PMCID: PMC10453311 DOI: 10.3390/cancers15164159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/12/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Within the oligometastatic state, oligorecurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally, it is an emergent situation that we are facing more frequently mainly due to (a) the incorporation into clinical practice of the PSMA-PET that provides strikingly increased superior images in comparison to conventional imaging, with higher sensitivity and specificity; (b) the higher detection rates of bone and node disease with extremely low levels of PSA; and (c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improving the clinical outcome. In this work, we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging-guided SBRT for the treatment of nodal recurrence in prostate cancer.
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Affiliation(s)
- Almudena Zapatero
- Health Research Institute, University Hospital La Princesa, 28006 Madrid, Spain
| | | | | | - Diego Aldave
- University Clinical Hospital of Valladolid, 47003 Valladolid, Spain;
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Tsaur I, Blaheta RA, Dotzauer R, Brandt MP, Gandaglia G, Sinescu I, Mirvald C, Olivier J, Surcel C. Focal therapy for primary tumor and metastases in de novo or recurrent oligometastatic prostate cancer: current standing and future perspectives. World J Urol 2023; 41:2077-2090. [PMID: 36183289 DOI: 10.1007/s00345-022-04162-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 07/08/2022] [Indexed: 10/07/2022] Open
Abstract
PURPOSE Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. METHODS For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. RESULTS Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. CONCLUSION Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition.
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Affiliation(s)
- Igor Tsaur
- Department of Urology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Roman A Blaheta
- Department of Urology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Robert Dotzauer
- Department of Urology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Maximilian P Brandt
- Department of Urology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Giorgio Gandaglia
- Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Ioanel Sinescu
- Center of Urologic Surgery, Dialysis and Renal Transplantation, Fundeni Clinical Institute, 00238, Bucharest, Romania
- University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Cristian Mirvald
- Center of Urologic Surgery, Dialysis and Renal Transplantation, Fundeni Clinical Institute, 00238, Bucharest, Romania
- University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
| | - Jonathan Olivier
- Department of Urology, Hospital Claude Huriez, CHU Lille, Lille, France
- Université de Lille Faculté de Médecine Henri Warembourg, Lille, France
- CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, Univ. Lille, 59000, Lille, France
| | - Cristian Surcel
- Center of Urologic Surgery, Dialysis and Renal Transplantation, Fundeni Clinical Institute, 00238, Bucharest, Romania.
- University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
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20
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Andriole GL, Scarsbrook AF, Savir-Baruch B. Impact of 18F-fluciclovine PET/CT on plans for androgen deprivation therapy in patients with biochemical recurrence of prostate cancer: data analysis from two prospective clinical trials. Urol Oncol 2023; 41:293.e1-293.e7. [PMID: 37121865 DOI: 10.1016/j.urolonc.2023.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/02/2023] [Accepted: 04/01/2023] [Indexed: 05/02/2023]
Abstract
INTRODUCTION Despite early detection and primary therapy improvements, biochemical recurrence (BCR) of prostate cancer remains common. The advent of highly sensitive molecular imaging has facilitated identification of men with limited metastatic disease burden that might be more optimally treated with metastases-directed therapy than with androgen deprivation therapy (ADT). The LOCATE (NCT02680041) and FALCON (NCT02578940) trials assessed the impact of 18F-fluciclovine PET/CT on the management of patients with BCR after curative-intent primary therapy. We performed a secondary analysis of LOCATE and FALCON data to characterize sites of recurrence and management decisions for BCR patients who had an intended management plan including ADT prior to undergoing 18F-fluciclovine PET/CT. METHODS Data from 317 LOCATE/FALCON patients who underwent 18F-fluciclovine PET/CT were analyzed and those with a prescan plan for ADT (± another treatment) were selected. 18F-Fluciclovine detection rates were determined at the patient level and for the prostate/prostate bed region, pelvic and extra-pelvic lymph nodes (LN), soft tissues, and bones. The patients' pre- and postscan treatment plans were compared and were stratified by imaging results. RESULTS A total of 146 patients had a prescan plan for ADT (60 as monotherapy and 86 in combination with another modality). 18F-Fluciclovine detected lesions in 85 of 146 (58%) patients planned for ADT. Detection rates in the prostate/bed, pelvic LN, extra-pelvic LN, soft tissues and bone were 30%, 25%, 13%, 2.1%, and 13%, respectively. Twenty-five (17%) patients had positivity confined to the prostate/bed, 21 (14%) had 18F-fluciclovine-positive pelvic LN (±prostate/bed) but no other involvement and 39 (27%) had involvement outside the prostate/bed and pelvic LN. Postscan, 93 of 146 (64%) patients had a management change, 55 (59%) of which were to abort ADT. Only 25% of the patients originally planned for ADT monotherapy still had an unaltered plan for ADT monotherapy postscan. Patients with a postscan plan for ADT monotherapy had the most disseminated disease. Disease in the prostate/bed only was most common in those whose plan was altered to abort ADT. CONCLUSIONS 18F-Fluciclovine-PET/CT influenced management plans for the majority of patients with a prescan plan for ADT. Plans were commonly amended to target salvage therapy for lesions identified with 18F-fluciclovine PET/CT, and consequently likely spared/delayed patients the morbidity associated with ADT.
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Affiliation(s)
| | - Andrew F Scarsbrook
- Leeds Teaching Hospitals NHS Trust, Leeds, UK; University of Leeds, Leeds, UK
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21
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Li X, Xi H, Cheng X, Yu Y, Zhang C, Wang G, Zhou X. Assessment of oligometastasis status of prostate cancer following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone using PSA percentage decline rate. Front Endocrinol (Lausanne) 2023; 14:1123934. [PMID: 36843605 PMCID: PMC9951113 DOI: 10.3389/fendo.2023.1123934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 01/31/2023] [Indexed: 02/11/2023] Open
Abstract
Objective To compare the tumor control in prostate cancer patients with oligo-metastasis following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone based on total prostate-specific antigen (tPSA) assessment. Methods Medical data of a total of 18 prostate cancer patients with oligometastasis administered in The First Affiliated Hospital of Nanchang University from March 2017 to March 2018 were prospectively collected. 10 patients received a combined therapy of robot-assisted radical prostatectomy and pharmaceutical androgen deprivation (RARP+ADT group), while 8 patients received pharmaceutical androgen deprivation therapy alone (ADT group). Then demographic characteristics, prostate volume, tumor characteristics and tPSA data were analysised and compared. Statistical analysis was performed using t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. Results No significant difference was found in patients' age (p = 0.075), prostate volume (p = 0.134) and number of bone metastasis (p = 0.342). Pre-treatment Gleason score was significantly lower in RA group (p = 0.003). Patients in RARP+ADT group had significantly lower pre-treatment tPSA (p = 0.014), while no statistical difference was noted in reexamined tPSA (p = 0.140) on follow-up. No statistical difference was noted in tPSA decline rates (declined tPSA value per day) in RARP+ADT and ADT group (8.1 ± 4.7 verse 7.5 ± 8.0 ng/ml/d, p = 0.853). However, tPSA percentage decline rate (declined tPSA percentage per day) was significantly higher in RARP+ADT group (11.6 ± 1.5%/d verses 2.9 ± 2.2%/d, p< 0.001). Immediate urinary continence was achieved in 9 patients (90%) upon removal of urethral catheter on post-operative day 7 in RARP+ADT group. Conclusion ADT alone and in combination with RARP both provide effective tumor control in patients suffering from prostate cancer with oligometastasis. ADT combined with RARP exhibited significant advantage in PSA percentage decline rate without compromising patients' urinary continence. Long-term tumor control requires further follow-up.
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Affiliation(s)
| | | | | | | | | | - Gongxian Wang
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaochen Zhou
- Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Chen JJ, Weg E, Liao JJ. Prostate and metastasis-directed focal therapy in prostate cancer: hype or hope? Expert Rev Anticancer Ther 2023; 23:163-176. [PMID: 36718727 DOI: 10.1080/14737140.2023.2171991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
INTRODUCTION The paradigm of focal therapy's role in metastatic patients is being challenged by evolving attitudes and emerging data. At the current time, specifically regarding prostate cancer, does the evidence indicate this is more hype or hope? AREAS COVERED We searched the literature via PubMed, MEDLINE, and Embase for studies from 2014 to the present addressing focal therapy with non-palliative intent in metastatic prostate cancer patients, emphasizing prospective trials when available. We sought to address all common clinical scenarios: de novo synchronous diagnosis, oligorecurrence, oligoprogression, and mCRPC disease. EXPERT OPINION Current evidence is strongest, and in our opinion practice-changing, for prostate-directed RT in de novo metastatic patients with low metastatic burden. Metastasis-directed therapy with SBRT is consistently shown to have low rates of toxicity, and promising rates of ADT-free survival and progression-free survival. These can be utilized on a patient-by-patient basis with these endpoints in mind, but do not yet show sufficient benefit to be standard of care. This is a rich area of ongoing research, and many trials should publish in the coming years to shed light on many unanswered questions, including the role of cytoreductive prostatectomy, systemic therapy combined with MDT, and the integration of modern PET imaging.
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Affiliation(s)
- Jonathan J Chen
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Emily Weg
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
| | - Jay J Liao
- Department of Radiation Oncology, University of Washington, Seattle, WA, USA
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Laughlin BS, Voss MM, Toesca DA, Daniels T, Golafshar MA, Keole SR, Wong WW, Rwigema JC, Davis B, Schild SE, Stish BJ, Choo R, Lester S, DeWees TA, Vargas CE. Preliminary Analysis of a Phase II Trial of Stereotactic Body Radiation Therapy for Prostate Cancer With High-Risk Features After Radical Prostatectomy. Adv Radiat Oncol 2022; 8:101143. [PMID: 36845611 PMCID: PMC9943785 DOI: 10.1016/j.adro.2022.101143] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 11/30/2022] [Indexed: 12/14/2022] Open
Abstract
Purpose There are limited data regarding using stereotactic body radiation therapy (SBRT) in the postprostatectomy setting. Here, we present a preliminary analysis of a prospective phase II trial that aimed to evaluate the safety and efficacy of postprostatectomy SBRT for adjuvant or early salvage therapy. Materials and Methods Between May 2018 and May 2020, 41 patients fulfilled inclusion criteria and were stratified into 3 groups: group I (adjuvant), prostate-specific antigen (PSA) < 0.2 ng/mL with high-risk features including positive surgical margins, seminal vesicle invasion, or extracapsular extension; group II (salvage), with PSA ≥ 0.2 ng/mL but < 2 ng/mL; or group III (oligometastatic), with PSA ≥ 0.2 ng/mL but < 2 ng/mL and up to 3 sites of nodal or bone metastases. Androgen deprivation therapy was not offered to group I. Androgen deprivation therapy was offered for 6 months for group II and 18 months for group III patients. SBRT dose to the prostate bed was 30 to 32 Gy in 5 fractions. Baseline-adjusted physician reported toxicities (Common Terminology Criteria for Adverse Events), patient reported quality-of-life (Expanded Prostate Index Composite, Patient-Reported Outcome Measurement Information System), and American Urologic Association scores were evaluated for all patients. Results The median follow-up was 23 months (range, 10-37). SBRT was adjuvant in 8 (20%) patients, salvage in 28 (68%), and salvage with the presence of oligometastases in 5 (12%) patients. Urinary, bowel, and sexual quality of life domains remained high after SBRT. Patients tolerated SBRT with no grade 3 or higher (3+) gastrointestinal or genitourinary toxicities. The baseline adjusted acute and late toxicity grade 2 genitourinary (urinary incontinence) rate was 2.4% (1/41) and 12.2% (5/41). At 2 years, clinical disease control was 95%, and biochemical control was 73%. Among the 2 clinical failures, 1 was a regional node and the other a bone metastasis. Oligometastatic sites were salvaged successfully with SBRT. There were no in-target failures. Conclusions Postprostatectomy SBRT was very well tolerated in this prospective cohort, with no significant effect on quality of life metrics postirradiation, while providing excellent clinical disease control.
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Affiliation(s)
| | - Molly M. Voss
- Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, Arizona
| | | | - Thomas Daniels
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona,Department of Radiation Oncology, NYU Langone Health, Brooklyn, New York
| | | | - Sameer R. Keole
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | - William W. Wong
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona
| | | | - Brian Davis
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | - Brad J. Stish
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Richard Choo
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Scott Lester
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Todd A. DeWees
- Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, Arizona
| | - Carlos E. Vargas
- Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona,Corresponding author: Carlos E. Vargas, MD
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Zilli T, Achard V, Dal Pra A, Schmidt-Hegemann N, Jereczek-Fossa BA, Lancia A, Ingrosso G, Alongi F, Aluwini S, Arcangeli S, Blanchard P, Conde Moreno A, Couñago F, Créhange G, Dirix P, Gomez Iturriaga A, Guckenberger M, Pasquier D, Sargos P, Scorsetti M, Supiot S, Tree AC, Zapatero A, Le Guevelou J, Ost P, Belka C. Recommendations for radiation therapy in oligometastatic prostate cancer: An ESTRO-ACROP Delphi consensus. Radiother Oncol 2022; 176:199-207. [PMID: 36228761 DOI: 10.1016/j.radonc.2022.10.005] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 10/07/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND PURPOSE Oligometastatic prostate cancer is a new and emerging treatment field with only few prospective randomized studies published so far. Despite the lack of strong level I evidence, metastasis-directed therapies (MDT) are widely used in clinical practice, mainly based on retrospective and small phase 2 studies and with a large difference across centers. Pending results of ongoing prospective randomized trials, there is a clear need for more consistent treatment indications and radiotherapy practices. MATERIAL AND METHODS A European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee consisting of radiation oncologists' experts in prostate cancer was asked to answer a dedicated questionnaire, including 41 questions on the main controversial issues with regard to oligometastatic prostate cancer. RESULTS The panel achieved consensus on patient selection and routine use of prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging as preferred staging and restaging imaging. MDT strategies are recommended in the de novo oligometastatic, oligorecurrent and oligoprogressive disease setting for nodal, bone and visceral metastases. Radiation therapy doses, volumes and techniques were discussed and commented. CONCLUSION These recommendations have the purpose of providing standardization and consensus to optimize the radiotherapy treatment of oligometastatic prostate cancer until mature results of randomized trials are available.
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Affiliation(s)
- Thomas Zilli
- Department of Radiation Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland.
| | - Vérane Achard
- Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland
| | - Alan Dal Pra
- Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, United States
| | | | - Barbara Alicja Jereczek-Fossa
- Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy; Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Milan, Italy
| | - Andrea Lancia
- Department of Radiation Oncology, Policlinico San Matteo Pavia Fondazione IRCCS, Pavia, Italy
| | - Gianluca Ingrosso
- Department of Radiation Oncology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Filippo Alongi
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy; University of Brescia, Brescia, Italy
| | - Shafak Aluwini
- Department of Radiation Oncology, University Medical Center Groningen, Groningen, the Netherlands
| | - Stefano Arcangeli
- Department of Radiation Oncology, School of Medicine and Surgery, University of Milan Bicocca, Milan, Italy
| | - Pierre Blanchard
- Université Paris Saclay, Villejuif, France; Inserm U1018 Oncostat, Department of Radiation Oncology, Gustave Roussy, Villejuif, France
| | - Antonio Conde Moreno
- Radiation Oncology Department, Hospital Universitario y Politécnico La Fe, Valencia, CEU Cardenal Herrera University, Castellón, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Madrid, Spain; Department of Radiation Oncology, Hospital La Luz, Madrid, Spain; Medicine Department, School of Biomedical Sciences, Universidad Europea, Villaviciosa de Odón, Madrid, Spain
| | - Gilles Créhange
- Department of Radiation Oncology, Institut Curie, Paris, France
| | - Piet Dirix
- Department of Radiation-Oncology, Iridium Network, Antwerp, Belgium
| | - Alfonso Gomez Iturriaga
- Biocruces Health Research Institute, Cruces University Hospital, Basque Country University (UPV/EHU), Barakaldo, Bizkaia, Spain
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - David Pasquier
- Academic Department of Radiation Oncology, Centre Oscar Lambret, Lille, France; CRIStAL UMR CNRS 9189, Lille University, Lille, France
| | - Paul Sargos
- Department of Radiotherapy, Institut Bergonié, Bordeaux, France
| | - Marta Scorsetti
- Radiotherapy and Radiosurgery Department, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Stéphane Supiot
- Department of Radiation Oncology, Institut de Cancérologie de l'Ouest René Gauducheau, Saint-Herblain, France
| | - Alison C Tree
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Almudena Zapatero
- Department of Radiation Oncology, Health Research Institute, University Hospital La Princesa, Madrid, Spain
| | - Jennifer Le Guevelou
- Department of Radiation Oncology, Geneva University Hospital, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland
| | - Piet Ost
- Department of Human Structure and Repair, Ghent University, Ghent, Belgium; Department of Radiation Oncology, Iridium Network, GZA ziekenhuizen, Wilrijk, Belgium
| | - Claus Belka
- Department of Radiation Oncology, LMU University Hospital Munich, Munich, Germany
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Sánchez-Iglesias ÁL, Morillo-Macías V, Santafé-Jiménez A, Ferrer-Albiach C. Bone-only oligometastatic prostate cancer: can SABR improve outcomes? A single-center experience. Radiat Oncol J 2022; 40:192-199. [PMID: 36200308 PMCID: PMC9535412 DOI: 10.3857/roj.2022.00101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 08/25/2022] [Indexed: 11/16/2022] Open
Abstract
Purpose Ablative treatment of oligometastases has shown survival benefit with certain tumors, although these effects still are to be demonstrated in prostate cancer. Materials and Methods We analysed the toxicity and clinical control results obtained in patients with bone-only oligometastatic prostate cancer treated with stereotactic ablative radiotherapy (SABR). Retrospective study on patients with metachronous oligoprogression and synchronous de novo bone-only oligometastatic prostate cancer treated with SABR and androgen deprivation therapy. Results Treatment schedules varied according to location and organs at risk, with biologically equivalent dose (BED) ≥100 Gy. Fifty-five bone lesions (31 patients) were treated and evaluated for toxicity, local control, progression-free survival (PFS), and overall survival (OS). After a 41-month follow-up, there was minimal acute or chronic toxicity and no G3 toxicity. The local control at 3 and 5 years was 100% and 87.1%, respectively. Median PFS and OS were 43 and 98 months, respectively. The best result in PFS was obtained with BED ≥230 Gy, delaying time to the next systemic therapy by 28.5 months. Conclusion The use of SABR in bone oligometastases of prostate cancer is safe with minimal toxicity and excellent results in local control and PFS, delaying the start of the next systemic therapy.
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Affiliation(s)
- Ángel L. Sánchez-Iglesias
- Department of Radiation Oncology, Consorcio Hospitalario Provincial de Castellón, Spain
- Correspondence: Ángel L. Sánchez-Iglesias Department of Radiation Oncology, Consorcio Hospitalario Provincial de Castellón, Avda. Dr. Clará 19, 12002 Castellón, Spain. Tel: +34-964-376000 Fax: +34-964-354401 E-mail:
| | | | - Ana Santafé-Jiménez
- Department of Radiation Oncology, Consorcio Hospitalario Provincial de Castellón, Spain
| | - Carlos Ferrer-Albiach
- Department of Radiation Oncology, Consorcio Hospitalario Provincial de Castellón, Spain
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Ingrosso G, Bottero M, Becherini C, Caini S, Alì E, Lancia A, Ost P, Sanguineti G, Siva S, Zilli T, Francolini G, Bellavita R, Aristei C, Livi L, Detti B. A systematic review and meta-analysis on non-metastatic castration resistant prostate cancer: The radiation oncologist's perspective. Semin Oncol 2022; 49:409-418. [PMID: 36192243 DOI: 10.1053/j.seminoncol.2022.09.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 09/08/2022] [Accepted: 09/09/2022] [Indexed: 11/11/2022]
Abstract
Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial response rates, a progression to a state of castration resistance is observed in most of the patients. In the present article, we conducted a systematic review and meta-analysis of all clinical trials assessing treatment for nmCRPC with next-generation androgen receptor inhibitors. We performed a review and meta-analysis of phase III randomized controlled trials comparing new agents (apalutamide, enzalutamide, darolutamide) with placebo as control arm, in the setting of nmCRPC. Patients treated with next-generation ARIs had a 26% reduction in the risk of death compared with placebo; compared with other ARIs, darolutamide had the lowest rate of grade 3 and 4 AEs and the lowest therapy discontinuation rate due to any grade AEs. This meta-analysis shows that treatment with new ARIs is safe and significantly reduces the risk of death and of metastasis onset in nmCRPC patients. Under way studies on new biomarkers such as genomic classifiers will probably allow the stratification in more specific subsets of disease. New imaging modalities such as PSMA-PET have shown greater sensibility and specificity than conventional imaging in metastases detection. All patients were randomized in a 2:1 fashion, with a total of 2,694 who underwent next-generation ARIs (806 apalutamide, 955 darolutamide, 933 enzalutamide) and 1,423 in the placebo arm.
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Affiliation(s)
- Gianluca Ingrosso
- Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Italy
| | - Marta Bottero
- Department of Radiation Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Carlotta Becherini
- Radiation Oncology, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
| | - Saverio Caini
- Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention, and Clinical Network (ISPRO), Florence, Italy
| | - Emanuele Alì
- Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Italy
| | - Andrea Lancia
- Department of Radiation Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Piet Ost
- Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium
| | - Giuseppe Sanguineti
- Department of Radiation Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Shankar Siva
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Thomas Zilli
- Radiation Oncology Department. Geneva University Hospital, Geneva, Switzerland
| | - Giulio Francolini
- Radiation Oncology, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
| | - Rita Bellavita
- Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Italy
| | - Cynthia Aristei
- Radiation Oncology Section, Department of Surgical and Biomedical Science, University of Perugia, Italy
| | - Lorenzo Livi
- Radiation Oncology, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy
| | - Beatrice Detti
- Radiation Oncology, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy.
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Nodal and osseous oligometastatic prostate cancer: a cohort including the introduction of PSMA-PET/CT-guided stereotactic and hypofractionated radiotherapy with elective nodal therapy. J Cancer Res Clin Oncol 2022:10.1007/s00432-022-04229-1. [PMID: 36029331 DOI: 10.1007/s00432-022-04229-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 07/18/2022] [Indexed: 10/15/2022]
Abstract
PURPOSE Oligometastatic prostate cancer is heavily investigated, and conventionally fractionated elective nodal treatment appears to increase biochemical relapse-free (bRFS) survival. The novelty of this report is to present elective nodal radiotherapy (ENRT) with simultaneous integrated boost with stereotactic (SBRT) or hypofractionated radiotherapy (HoFRT) for tolerance and for bRFS which we compared with SBRT of the involved field (IF) only. MATERIALS AND METHODS Patients between 2018 and 2021 with and oligometastatic prostate cancer treated with SBRT or hypofractionation were eligible. A radiobiologically calculated simultaneous integrated boost approach enabled to encompass elective nodal radiotherapy (ENRT) with high doses to PSMA-positive nodes. A second group had only involved field (IF) nodal SBRT. RESULTS A total of 44 patients with 80 lesions of initially intermediate- (52%) or high-risk (48%) D'Amico omPC were treated with SBRT to all visible PSMA-PET/CT lesions and 100% of the treated lesions were locally controlled after a median follow-up was 18 months (range 3-42 months). Most lesions (56/80; 70%) were nodal and the remainder osseous. Median bPFS was 16 months and ADT-free bPFS 18 months. ENRT (31 patients) versus IF (13 patients) prevented regional relapse more successfully. At univariate analysis, both initial PSA and length of the interval between primary diagnosis and biochemical failure were significant for biochemical control. Treatment was well tolerated and only two patients had toxicity ≥ grade 3 (1 GU and 1 GI, each). DISCUSSION/CONCLUSION SBRT and hypofractionated radiotherapy at curative doses with ENRT was more effective to delay ADT than IF, controlled all treated lesions and was well tolerated.
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Alberto M, Yim A, Papa N, Siva S, Ischia J, Touijer K, Eastham JA, Bolton D, Perera M. Role of PSMA PET-guided metastases-directed therapy in oligometastatic recurrent prostate cancer. Front Oncol 2022; 12:929444. [PMID: 36059632 PMCID: PMC9433573 DOI: 10.3389/fonc.2022.929444] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 07/28/2022] [Indexed: 11/13/2022] Open
Abstract
Oligometastatic prostate cancer (OMPC) has been proposed as an intermediary state between localised disease and widespread metastases, with varying definitions including 1, 3, or ≤5 visceral or bone metastasis. Traditional definitions of OMPC are based on staging with conventional imaging, such as computerised tomography (CT) and whole-body bone scan (WBBS). Novel imaging modalities such as prostate-specific membrane antigen positron emission tomography (PSMA PET) have improved diagnostic utility in detecting early metastatic prostate cancer (PC) metastases compared with conventional imaging. Specifically, meta-analytical data suggest that PSMA PET is sensitive in detecting oligometastatic disease in patients with biochemical recurrence (BCR) post-radical treatment of PC. Recent trials have evaluated PSMA PET-guided metastases-directed therapy (MDT) in oligometastatic recurrent disease, typically with salvage surgery or radiotherapy (RT). To date, these preliminary studies demonstrate promising results, potentially delaying the need for systemic therapy. We aim to report a comprehensive, multidisciplinary review of PSMA-guided MDT in OMPC. In this review, we highlight the utility of PMSA PET in biochemically recurrent disease and impact of PSMA PET on the definition of oligometastatic disease and outline data pertaining to PSMA-guided MDT.
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Affiliation(s)
- Matthew Alberto
- Department of Surgery, Austin Health, University of Melbourne, Melbourne, VIC, Australia
| | - Arthur Yim
- Department of Surgery, Austin Health, University of Melbourne, Melbourne, VIC, Australia
| | - Nathan Papa
- Department of Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Shankar Siva
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Joseph Ischia
- Department of Surgery, Austin Health, University of Melbourne, Melbourne, VIC, Australia
| | - Karim Touijer
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - James A. Eastham
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Damien Bolton
- Department of Surgery, Austin Health, University of Melbourne, Melbourne, VIC, Australia
| | - Marlon Perera
- Department of Surgery, Austin Health, University of Melbourne, Melbourne, VIC, Australia
- Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
- *Correspondence: Marlon Perera,
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Ruiz Aragón J, Jiménez Varo E, Ruiz Aragón AI, Revelo Cadena I, Agüera Sánchez Á, Jiménez Romero ME. Cytoreductive surgery in patients with oligometastatic prostate cancer. Systematic review of the scientific literature. Actas Urol Esp 2022:S2173-5786(22)00076-2. [PMID: 36319558 DOI: 10.1016/j.acuroe.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/05/2022] [Indexed: 06/16/2023]
Abstract
INTRODUCTION Interest in oligometastatic prostate cancer has spiked due to the emergence of new evidence regarding more specific and accurate imaging, and the wider use of minimally invasive techniques. Nevertheless, the optimal management of this pathology is yet to be determined. OBJECTIVE Assess the efficacy and safety of cytoreductive surgery in patients suffering from oligometastatic prostate cancer. EVIDENCE GATHERING Systematic review of the scientific literature (01/01/2010-31/12/2021) within the MedLine, Embase, Cochrane Library, Cinahl, Scopus, Spanish Healthcare Technology Assessment Agencies (AETS, Agencias de Evaluación de Tecnologías Sanitarias) and ClinicalTrials.gov databases. The keywords used were prostatectomy, prostatic neoplasm, radical prostatectomy; the free search terms were prostatectomy and oligometastatic prostate. The inclusion criteria comprised studies on patients with oligometastatic prostate cancer who had been operated on using radical cytoreductive prostatectomy. EVIDENCE SYNTHESIS The systematic review included 4 observational studies, 2 clinical trials, and 2 case series, of moderate quality. The results observed suggest that oligometastatic prostate cancer patients who had undergone cytoreductive prostate surgery obtained a benefit in terms of efficacy. Conversely, the majority of these studies showed a reduction in the number of localized complications, when compared to the best systemic treatments. CONCLUSIONS Cytoreductive surgery in this group of patients is a safe procedure that reduces the incidence of localized complications and that presents promising results with regard to survival rates. To date, the lack of prospective trials limits the use of this therapeutic option to experimental environments.
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Affiliation(s)
- J Ruiz Aragón
- Microbiología Clínica, Laboratorios, Clínicos, Hospital de la Línea, Cádiz, Spain
| | - E Jiménez Varo
- Análisis Clínicos, Laboratorios Clínicos, Hospital de la Línea, Cádiz, Spain
| | - A I Ruiz Aragón
- Inspectora Salud pública, Campo de Gibraltar Oeste, Cádiz, Spain
| | - I Revelo Cadena
- Servicio de Urología, Hospital Universitario Puerto Real, Cádiz, Spain
| | - Á Agüera Sánchez
- Servicio de Urología, Hospital Universitario Puerto Real, Cádiz, Spain
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Chinniah S, Stish B, Costello BA, Pagliaro L, Childs D, Quevedo F, Lucien F, Bryce A, Park SS, Orme JJ. Radiotherapy in Oligometastatic Prostate Cancer. Int J Radiat Oncol Biol Phys 2022; 114:684-692. [PMID: 35878715 DOI: 10.1016/j.ijrobp.2022.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/12/2022] [Accepted: 07/16/2022] [Indexed: 10/31/2022]
Abstract
Prostate cancer ranges from localized, low risk to metastatic, morbid disease. While radiotherapy is commonly incorporated in the treatment of early disease or for palliation of symptomatic lesions, its role in extending survival in metastatic disease is less well-established. Here, we review the available evidence surrounding localized radiotherapy in the presence of oligometastatic disease and metastasis-directed therapy in both hormone-sensitive and hormone-resistant prostate cancer. We further outline potential future incorporation of radiotherapy as an immune-sensitizing therapy and the importance of highly sensitive imaging modalities in considering radiotherapy in metastatic disease.
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Affiliation(s)
| | - Bradley Stish
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN
| | | | - Lance Pagliaro
- Division of Medical Oncology, Mayo Clinic, Rochester, MN
| | - Daniel Childs
- Division of Medical Oncology, Mayo Clinic, Rochester, MN
| | | | | | - Alan Bryce
- Department of Hematology and Oncology, Mayo Clinic, Phoenix, AZ
| | - Sean S Park
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN
| | - Jacob J Orme
- Division of Medical Oncology, Mayo Clinic, Rochester, MN.
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31
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Thomas MC, Chen YH, Fite E, Pangilinan A, Bubelo K, Spektor A, Balboni TA, Huynh MA. Patient and Treatment Factors Associated with Improved Local Control and Survival in Oligometastatic Bone Disease: Results from a Large Single-Institution Experience Using Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys 2022; 114:747-761. [PMID: 35840113 DOI: 10.1016/j.ijrobp.2022.06.096] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/27/2022] [Accepted: 06/28/2022] [Indexed: 10/31/2022]
Abstract
PURPOSE Limited data exists to guide optimal patient selection and treatment of bone metastases with curative intent despite the increasing application of stereotactic body radiation therapy (SBRT) for oligometastatic (OM) disease control and re-irradiation(ReRT). METHODS Clinical characteristics for 434 patients consecutively treated with bone SBRT at a single institution from 3/2011-6/2020 were analyzed by OM, spine, and non-spine bone using Cox regression to determine association with local control (LC), progression-free survival (PFS), and overall survival (OS), and the Kaplan-Meier method to estimate PFS and OS. RESULTS Most patients had prostate (39%) or breast/lung (21%) cancer and 1-3 lesions (96%), with 651 lesions (spine 63%) treated for ReRT (12%) or OMD (88%), including synchronous (10%), metachronous (28%), repeat (27%), or induced (23%) states as defined by ESTRO/EORTC criteria. Biologically effective dose (BED10) ≥50 (HR 0.68, CI 0.48-0.96, p<0.03) predicted improved LC among OM lesions and planning target volume (PTV)≥150 cc (HR 1.94, CI 1.02 to 3.70, p<0.04) predicted worse LC for non-spine bone. Prostate histology, performance status (PS) 0-1, and MFI ≥2 year predicted improved PFS and OS (p<0.05). Metachronous, synchronous, or repeat OM had higher PFS and OS (p≤0.001) than induced OM. With median follow-up 25.7 months, 1 and 2-year PFS was 63% and 47% for OM and 36% and 25% for ReRT;1 and 2-yr OS was 87% and 73% for OM, 58% and 43% for ReRT. Acute toxicities included grade 1-2 pain flare (9%) and fatigue (14%). Late toxicities included fracture (1%) for OM and myelopathy (2.5%) or nerve pain (1.2%) for ReRT. CONCLUSIONS BED10 ≥ 50 for OM and PTV<150cc for non-spine bone lesions was associated with improved LC. Prostate histology, PS 0-1, MFI≥2 years, and metachronous, synchronous, or repeat presentations per EORTC/ESTRO OM criteria predicted improved PFS and OS among OM patients treated with bone SBRT.
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Affiliation(s)
- Maria C Thomas
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Yu-Hui Chen
- Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Elliot Fite
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew Pangilinan
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Katerina Bubelo
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Alexander Spektor
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Tracy A Balboni
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Mai Anh Huynh
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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Completeness of reporting oligometastatic disease characteristics in literature and influence on oligometastatic disease classification using the ESTRO/EORTC nomenclature. Int J Radiat Oncol Biol Phys 2022; 114:587-595. [PMID: 35738308 DOI: 10.1016/j.ijrobp.2022.06.067] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 06/06/2022] [Accepted: 06/09/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND There is increasing evidence for the integration of locally ablative therapy into multimodality treatment of oligometastatic disease (OMD). To support standardised data collection, analysis, and comparison, a consensus OMD classification based on fundamental disease and treatment characteristics has previously been established. This study investigated the completeness of reporting the proposed OMD characteristics in literature and evaluated whether the proposed OMD classification system can be applied to the historical data. METHODS A systematic literature review was performed in Medline, Embase, and Cochrane, searching for prospective and retrospective studies, where SBRT was a treatment component of OMD. Reporting of the OMD characteristics as described in the EORTC/ESTRO classification was analyzed, feasibility to retrospectively classify the proposed OMD states was investigated and the impact of the categorisation on overall survival (OS) was evaluated. RESULTS Our study shows incomplete reporting of the proposed OMD characteristics. The most fully reported characteristic was 'type of involved organs' (88/95 studies); 'history of cancer progression' was the least reported (not mentioned in 50/95 studies). Retrospective OMD classification of existing literature was only possible for 7/95 studies. With respect to categorization as de novo, repeat or induced OMD, homogeneous patient cohorts were observed in 21/95 studies, most frequently de novo OMD, in 20 studies. Differences in OS at 2, 3, or 5 years were not statistically significant between the different states. OS was significantly influenced by primary tumor histology, with superior OS observed for prostate cancer and worst OS observed for non-small cell lung cancer. CONCLUSION The largely incomplete reporting of the proposed OMD characteristics hampers a retrospective classification of existing literature. To facilitate future comparison of individual studies, as well as validation of the OMD classification, comprehensive reporting of OMD characteristics using standardised terminology is recommended, as proposed by the EORTC/ESTRO classification system and following ESTRO-ASTRO consensus.
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Stratification of Oligometastatic Prostate Cancer Patients by Liquid Biopsy: Clinical Insights from a Pilot Study. Biomedicines 2022; 10:biomedicines10061321. [PMID: 35740343 PMCID: PMC9219949 DOI: 10.3390/biomedicines10061321] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 05/29/2022] [Accepted: 06/02/2022] [Indexed: 02/01/2023] Open
Abstract
We propose a pilot, prospective, translational study with the aim of identifying possible molecular markers underlying metastatic prostate cancer (PC) evolution with the use of liquid biopsy. Twenty-eight castrate sensitive, oligometastatic PC patients undergoing bone and/or nodal stereotactic body radiotherapy (SBRT) were recruited. Peripheral blood samples were collected before the commencement of SBRT, then they were processed for circulating cell free DNA (cfDNA) extraction. Deep targeted sequencing was performed using a custom gene panel. The primary endpoint was to identify differences in the molecular contribution between the oligometastatic and polymetastatic evolution of PC to same-first oligo-recurrent disease presentation. Seventy-seven mutations were detected in 25/28 cfDNA samples: ATM in 14 (50%) cases, BRCA2 11 (39%), BRCA1 6 (21%), AR 13 (46%), ETV4, and ETV6 2 (7%). SBRT failure was associated with an increased risk of harboring the BRCA1 mutation (OR 10.5) (p = 0.043). The median cfDNA concentration was 24.02 ng/mL for ATM mutation carriers vs. 40.04 ng/mL for non-carriers (p = 0.039). Real-time molecular characterization of oligometastatic PC may allow for the identification of a true oligometastatic phenotype, with a stable disease over a long time being more likely to benefit from local, curative treatments or the achievement of long-term disease control. A prospective validation of our promising findings is desirable for a better understanding of the real impact of liquid biopsy in detecting tumor aggressiveness and clonal evolution.
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Chakraborty S, Roychoudhury S. Pathological Roles of Reactive Oxygen Species in Male Reproduction. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1358:41-62. [PMID: 35641865 DOI: 10.1007/978-3-030-89340-8_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Reactive oxygen species (ROS) are free radicals that have at least one unpaired electron and play specific roles in the human body. An imbalance of ROS and antioxidant levels gives rise to a condition called oxidative stress. High levels of ROS in the male reproductive tract can interfere with its normal functioning and can even pose as toxic to the sperm, inhibiting sperm functioning (including motility) and metabolism. Oxidative stress resulting from ROS and lipid peroxidation is one of the major causes of male infertility including infertility in varicocele patients. These may cause DNA and peroxidative damage and apoptosis. Production of ROS in excess also leads to erectile dysfunction (ED). In recent years, studies have also linked oxidative stress with the development, progress, and therapy response of prostate cancer patients. The present study summarizes the pathological roles of ROS in male reproductive problems such as infertility, ED, and prostate cancer and also provide an insight into the probable mechanism through which ROS exert their pathological impact.
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Deodato F, Pezzulla D, Cilla S, Ferro M, Romano C, Bonome P, Buwenge M, Zamagni A, Strigari L, Valentini V, Morganti AG, Macchia G. Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis. Clin Transl Oncol 2022; 24:1177-1183. [PMID: 34984604 DOI: 10.1007/s12094-021-02764-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 12/20/2021] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Aim of this analysis was to report toxicity and clinical outcomes in oligorecurrent prostate cancer (PCa) patients treated with single fraction stereotactic radiosurgery (SRS) for bone metastases. METHODS We separately analyzed clinical data of PCa patients with bone oligometastases enrolled in a prospective phase I trial (DESTROY-2). DESTROY-2 was based on SRS delivered using volumetric modulated arc therapy in patients with primary or metastatic tumors in several extra-cranial body sites. Acute and late toxicity, biochemical tumor response, local control (LC), distant metastases-free (DPFS), progression-free (PFS), time to next-line systemic treatment-free (NEST-FS), and overall survival (OS) were calculated. RESULTS Data on 37 PCa patients, carrying out 50 bone metastases, candidates for curative-intent treatment and treated with SRS at our Institution were collected. SRS dose ranged between 12 and 24 Gy. One grade 1 acute skin toxicity in one patient treated on the hip (24 Gy) and one grade 1 late skin toxicity in a patient with a scapular lesion (24 Gy) were recorded. No cases of bone fracture were registered in the treated population. With a median follow-up of 25 months (range 3-72 months) 2-year actuarial LC, DPFS, PFS, and OS were 96.7%, 58.1%, 58.1%, and 95.8%, respectively. Median and 2-year NEST-FS were 30 months (range 1-69 months) and 51.2%, respectively. CONCLUSIONS Data analysis showed few toxicity events, high local control rate and prolonged NEST-FS after linear accelerator-based radiosurgery of bone oligometastases from PCa. The possibility of postponing systemic treatments in patients with oligometastatic PCa by means of SRS should be taken into account. Further prospective studies on larger series are needed to confirm the reported results.
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Affiliation(s)
- F Deodato
- Radiation Oncology Unit, Gemelli Molise S.P.A. Hospital, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy.,Radiology Institute, Università Cattolica del Sacro Cuore, 00135, Rome, Italy
| | - D Pezzulla
- Radiation Oncology Unit, Gemelli Molise S.P.A. Hospital, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy.
| | - S Cilla
- Medical Physics Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, Campobasso, Italy
| | - M Ferro
- Radiation Oncology Unit, Gemelli Molise S.P.A. Hospital, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - C Romano
- Medical Physics Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, Campobasso, Italy
| | - P Bonome
- Radiation Oncology Unit, Gemelli Molise S.P.A. Hospital, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
| | - M Buwenge
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Experimental, Diagnostic, and Specialty Medicine-DIMES, Alma Mater Studiorum Bologna University, Bologna, Italy
| | - A Zamagni
- Radiotherapy Department, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via Giuseppe Massarenti, Bologna, Italy
| | - L Strigari
- Medical Physics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - V Valentini
- Radiology Institute, Università Cattolica del Sacro Cuore, 00135, Rome, Italy.,Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A Gemelli IRCCS, UOC di Radioterapia Oncologica, Rome, Italy
| | - A G Morganti
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.,Department of Experimental, Diagnostic, and Specialty Medicine-DIMES, Alma Mater Studiorum Bologna University, Bologna, Italy
| | - G Macchia
- Radiation Oncology Unit, Gemelli Molise S.P.A. Hospital, Università Cattolica del S. Cuore, Largo A. Gemelli 1, 86100, Campobasso, Italy
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Ruiz Aragón J, Jiménez Varo E, Ruiz Aragón A, Revelo Cadena I, Agüera Sánchez Á, Jiménez Romero M. Cirugía citorreductora en pacientes con cáncer de próstata oligometastásico. Revisión sistemática de la literatura científica. Actas Urol Esp 2022. [DOI: 10.1016/j.acuro.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Patel PH, Tunariu N, Levine DS, de Bono JS, Eeles RA, Khoo V, Murray J, Parker CC, Pathmanathan A, Reid A, van As N, Tree AC. Oligoprogression in Metastatic, Castrate-Resistant Prostate Cancer-Prevalence and Current Clinical Practice. Front Oncol 2022; 12:862995. [PMID: 35656509 PMCID: PMC9152030 DOI: 10.3389/fonc.2022.862995] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 04/01/2022] [Indexed: 11/13/2022] Open
Abstract
Aims Oligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen receptor-targeted therapy (ARTT)]. The aim of this study was to determine the prevalence of oligoprogression, describe the characteristics of oligoprogression in a cohort of patients from a single center, and identify the number of patients potentially treatable with stereotactic body radiotherapy (SBRT). Methods Castration-resistant prostate cancer (CRPC) patients who radiologically progressed while on ARTT were included. Patients with oligoprogressive disease (OPD) (≤3 lesions) on any imaging were identified in a retrospective analysis of electronic patient records. Kaplan-Meier method and log-rank test were used to calculate progression-free and overall survival. Results A total of 102 patients with metastatic CRPC on ARTT were included. Thirty (29%) patients presented with oligoprogression (46 lesions in total); 21 (21% of total) patients had lesions suitable for SBRT. The majority of lesions were in the bone (21, 46%) or lymph nodes (15, 33%). Patients with oligoprogression while on ARTT had a significantly better prostate-specific antigen (PSA) response on commencing ARTT as compared to patients who later developed polyprogression. However, PSA doubling time immediately prior to progression did not predict OPD. Median progression-free survival to oligoprogression versus polyprogression was 16.8 vs. 11.7 months. Time to further progression after oligoprogression was 13.6 months in those treated with radiotherapy (RT) for oligoprogression vs. 5.7 months in those treated with the continuation of ARTT alone. Conclusions In this study, nearly a third of patients on ARTT for CRPC were found to have OPD. OPD patients had a better PSA response on ART and a longer duration on ARTT before developing OPD as compared to those developing polyprogressive disease (Poly-PD). The majority of patients (70%) with OPD had lesions suitable for SBRT treatment. Prospective randomized control trials are needed to establish if there is a survival benefit of SBRT in oligoprogressive prostate cancer and to determine predictive indicators.
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Affiliation(s)
- Priyanka H. Patel
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Nina Tunariu
- Radiology and Imaging, Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Daniel S. Levine
- Radiology and Imaging, Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Johann S. de Bono
- Drug Development Unit, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Rosalind A. Eeles
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Vincent Khoo
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Julia Murray
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Christopher C. Parker
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Angela Pathmanathan
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Alison Reid
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Nicholas van As
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
| | - Alison C. Tree
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom
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Janssen J, Staal FHE, Brouwer CL, Langendijk JA, de Jong IJ, van Moorselaar RJA, Schuit E, Verzijlbergen JF, Smeenk RJ, Aluwini S. Androgen Deprivation therapy for Oligo-recurrent Prostate cancer in addition to radioTherapy (ADOPT): study protocol for a randomised phase III trial. BMC Cancer 2022; 22:482. [PMID: 35501744 PMCID: PMC9063099 DOI: 10.1186/s12885-022-09523-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 04/08/2022] [Indexed: 11/10/2022] Open
Abstract
Background More than 60% of oligo-recurrent prostate cancer (PCa) patients treated with metastasis-directed radiotherapy (MDRT) develop biochemical recurrence within 2 years. This recurrence rate emphasises the need for improved treatment and patient selection. In line with the treatment of primary PCa, the efficacy of MDRT may be enhanced when combined with androgen-deprivation therapy (ADT). Furthermore, the availability of PSMA PET/CT offers an excellent tool for optimal patient selection for MDRT. This phase III randomised controlled trial will investigate the role of the addition of ADT to MDRT in oligo-recurrent PCa patients selected with PSMA PET/CT to enhance oncological outcome. Methods Two hundred and eighty patients will be randomised in a 1:1 ratio to the standard treatment arm (MDRT alone) or the experimental arm (MDRT + 6 months ADT). Patients with biochemical recurrence after primary treatment of PCa presenting with ≤ 4 metastases will be included. The primary endpoint is the 2.5-year metastases progression-free survival (MPFS). Secondary endpoints are acute and late toxicity, quality of life, biochemical progression-free survival, overall survival, and the sensitivity of the PSMA PET/CT for detecting oligometastases at low PSA-levels. So far, between March 2020 and December 2021, one hundred patients have been included. Discussion This phase III randomised controlled trial will assess the possible benefit of the addition of 6 months ADT to MDRT on metastases progression-free survival, toxicity, QoL and survival in PCa patients with 1–4 recurrent oligometastatic lesions. Trial registration ClinicalTrials.gov, NCT04302454. Registered 10 March 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09523-2.
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Affiliation(s)
- J Janssen
- Department of Radiation Oncology, University Medical Center Groningen, Hanzeplein 1, Postbus 30 001, 9700 RB, Groningen, the Netherlands.
| | - F H E Staal
- Department of Radiation Oncology, University Medical Center Groningen, Hanzeplein 1, Postbus 30 001, 9700 RB, Groningen, the Netherlands
| | - C L Brouwer
- Department of Radiation Oncology, University Medical Center Groningen, Hanzeplein 1, Postbus 30 001, 9700 RB, Groningen, the Netherlands
| | - J A Langendijk
- Department of Radiation Oncology, University Medical Center Groningen, Hanzeplein 1, Postbus 30 001, 9700 RB, Groningen, the Netherlands
| | - I J de Jong
- Department of Urology, University Medical Center Groningen, Groningen, the Netherlands
| | - R J A van Moorselaar
- Department of Urology, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - E Schuit
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - J F Verzijlbergen
- Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
| | - R J Smeenk
- Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - S Aluwini
- Department of Radiation Oncology, University Medical Center Groningen, Hanzeplein 1, Postbus 30 001, 9700 RB, Groningen, the Netherlands
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Detti B, Zilli T, Ingrosso G, Ribeiro I, Lancia A. Editorial: Interaction Between Modern Radiotherapy and Novel Drugs in Prostate Cancer: Future Perspectives. Front Oncol 2022; 12:876318. [PMID: 35433471 PMCID: PMC9005631 DOI: 10.3389/fonc.2022.876318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 02/28/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Beatrice Detti
- Azienda Ospedaliera Universitaria Careggi, Radiotherapy Unit, Firenze, Italy
| | - Thomas Zilli
- Radiation Oncology, Geneva University Hospital, Geneva, Switzerland
| | - Gianluca Ingrosso
- Radiation Oncology Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Ivone Ribeiro
- Radiation Oncology, University Hospital of Gran Canaria Dr. Negrin Las Palmas de Gran Canaria, Las Palmas, Spain
| | - Andrea Lancia
- Radiation Oncology, San Matteo Hospital Foundation (IRCCS) Pavia, Pavia, Italy
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Where Do We Stand in the Management of Oligometastatic Prostate Cancer? A Comprehensive Review. Cancers (Basel) 2022; 14:cancers14082017. [PMID: 35454924 PMCID: PMC9029666 DOI: 10.3390/cancers14082017] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/10/2022] [Accepted: 04/14/2022] [Indexed: 12/04/2022] Open
Abstract
Simple Summary Oligometastatic prostate cancer is an intermediate stage between localised and metastatic disease. Today, there are many advances in the diagnosis of this stage of the disease, with the appearance of new imaging techniques and treatments, thanks to the development of new modalities, both local and systemic therapies, the emergence of personalised medicine, and theragnostics. Abstract Oligometastatic prostate cancer (OMPC) is an intermediate state between localised disease and widespread metastases that includes a spectrum of disease biology and clinical behaviours. This narrative review will cover the current OMPC scenario. We conducted comprehensive English language literature research for original and review articles using the Medline database and grey literature through December 2021. OMPC is a unique clinical state with inherently more indolent tumour biology susceptible to multidisciplinary treatment (MDT). With the development of new imaging techniques, patients with OMPC are likely to be identified at an earlier stage, and the paradigm for treatment is shifting towards a more aggressive approach to treating potentially curable patients. Multimodal management is necessary to improve patient outcomes due to the combination of available therapies, such as local therapy of primary tumour, metastasis directed therapy or systemic therapy, to reduce tumour load and prevent further disease progression. Additional prospective data are needed to select patients most likely to benefit from a given therapeutic approach.
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Rogowski P, Trapp C, von Bestenbostel R, Konnerth D, Marschner S, Schmidt Hegemann NS, Belka C, Li M. Radiotherapy in oligometastatic prostate cancer-a pattern of care survey among members of the German Society for Radiation Oncology (DEGRO). Strahlenther Onkol 2022; 198:727-734. [PMID: 35364690 PMCID: PMC9300519 DOI: 10.1007/s00066-022-01925-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 03/02/2022] [Indexed: 11/30/2022]
Abstract
Purpose Due to improved imaging, oligometastatic prostate cancer (OMPC) is diagnosed more frequently. Growing evidence shows that patients with a limited number of metastases benefit from primary-directed radiotherapy (PDT) as well as from metastasis-directed radiotherapy (MDT). This survey investigates the current treatment practice for OMPC among German-speaking radiation oncologists. Methods Members of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie [DEGRO]) were surveyed regarding their current treatment practice via an anonymous online questionnaire sent by email. The survey included six general items and 14 specific items regarding treatment characteristics. Questionnaires with at least 50% of questions completed were considered for further analysis. Results A total of 204 responses were received (15% response rate), 167 were considered for further analysis. Most respondents stated to be specialized in treating prostate cancer patients and to treat 10–30 patients with OMPC per annum; 97% considered PSMA-PET/CT necessary to define oligometastatic disease. Opinions differed regarding the use of systemic therapies: 63% of the respondents aimed to defer systemic therapy using radiotherapy in OMPC, whereas 37% considered systemic therapy necessary. In the setting of synchronous OMPC, 97% recommended PDT with or without a combination of MDT and/or systemic therapy. For metachronous nodal or bone oligometastatic recurrence, 98 and 99%, respectively, would opt for MDT. The majority would combine MDT with systemic therapy in patients with metachronous oligorecurrence. Respondents recommended normofractionation, hypofractionation, and SBRT for lymph node metastases in 49, 27, and 24%, respectively. No consensus existed regarding the field size for MDT of lymph node metastases. Most respondents preferred > 5 fractions for treatment of bone metastases. Conclusion Local radiotherapy for PDT and MDT is routinely used among respondents of this survey, representing 12% of all German-speaking radiation oncologists. The timing of systemic therapy, fractionation schedules, and field sizes are handled differently and remain an area of active investigation.
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Affiliation(s)
- Paul Rogowski
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Christian Trapp
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Rieke von Bestenbostel
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Dinah Konnerth
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Sebastian Marschner
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | | | - Claus Belka
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.,German Cancer Consortium (DKTK), Munich, Germany
| | - Minglun Li
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
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Häggman M, Dahlman P, Ahlberg M, Liss P, Cantera Ahlman R, Dragomir A, Ladjevardi S. Bi-parametric MRI/TRUS fusion targeted repeat biopsy after systematic 10-12 core TRUS-guided biopsy reveals more significant prostate cancer especially in anteriorly located tumors. Acta Radiol Open 2022; 11:20584601221085520. [PMID: 35392628 PMCID: PMC8980410 DOI: 10.1177/20584601221085520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/15/2022] [Indexed: 11/15/2022] Open
Abstract
Background MRI and fusion guided biopsy have an increased role in the diagnosis of prostate cancer. Purpose To demonstrate the possible advantages with Bi-parametric MRI fusion-guided repeat biopsy over systematic 10-12-core biopsy for the diagnosis of prostate cancer. Material and Methods Four hundred and twenty-three consecutive men, with previous systematic 10-12-core TRUS-guided biopsy, and with suspicion of, or diagnosis of, low-risk prostate cancer underwent fusion-guided prostate biopsy between February 2015 and February 2017. The material was retrospectively assessed. In 220 cases no previous cancer was diagnosed, and in 203 cases confirmatory fusion guided biopsy was performed prior to active monitoring. MRI was classified according to PI-RADS. Systematic biopsy was compared to fusion guided biopsy for the detection of cancer, and PI-RADS was compared to the Gleason score. Results Fusion guided biopsy detected significantly more cancers than systematic (p < .001). Gleason scores were higher in the fusion biopsy group (p < .001). Anterior tumors were present in 54% of patients. Fusion biopsy from these lesions showed cancer in 53% with previously negative biopsy in systematic biopsies and 66% of them were upgraded from low risk to intermediate or high-risk cancers. Conclusion These results show superior detection rate and grading of bi-parametric MRI/TRUS fusion targeted repeat biopsy over systematic 10-12 core biopsies. Fusion guided biopsy detects more significant cancers despite using fewer cores. The risk group was changed for many patients initially selected for active surveillance due to upgrading of tumors. Bi-parametric MRI shows promising results in detecting anterior tumors in patients with suspected prostate cancer.
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Affiliation(s)
- Michael Häggman
- Department of Urology, Uppsala University Hospital, Uppsala, Sweden
| | - Pär Dahlman
- Department of Radiology, Uppsala University Hospital, Uppsala, Sweden
| | - Mats Ahlberg
- Department of Urology, Uppsala University Hospital, Uppsala, Sweden
| | - Per Liss
- Department of Radiology, Uppsala University Hospital, Uppsala, Sweden
| | | | - Anca Dragomir
- Department of Radiology, Uppsala University Hospital, Uppsala, Sweden
- Department of Pathology, Uppsala University Hospital, Uppsala, Sweden
| | - Sam Ladjevardi
- Department of Urology, Uppsala University Hospital, Uppsala, Sweden
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Mena E, Lindenberg L, Choyke P. The Impact of PSMA PET/CT Imaging in Prostate Cancer Radiation Treatment. Semin Nucl Med 2022; 52:255-262. [PMID: 35016755 PMCID: PMC8960055 DOI: 10.1053/j.semnuclmed.2021.12.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Imaging of prostate cancer is rapidly evolving with the introduction of the novel prostate-specific membrane antigen (PSMA)-targeted PET imaging tool for managing recurrent prostate cancer. One immediate impact of PSMA PET is the identification of residual or recurrent lesions that are amenable to external beam radiotherapy. Radiotherapy is used as a definitive curative treatment option for patients with localized prostate cancer alone or in combination therapy. In the setting of biochemical failure after radical prostatectomy, salvage radiation is a potential curative option, and the application of metastasis-directed radiotherapy in the setting of oligometastatic prostate cancer is currently being studied. To maximize the chances of curative therapy, the irradiated tumor volumes should completely encompass the actual extent of disease. Thus, an accurate estimation of the location and delineation of disease targets is critical for radiotherapy planning. The integration of PSMA PET imaging into the routine evaluation of prostate cancer has markedly improved sensitivity and specificity for recurrent disease, even at very low PSA values, which may enable further tailored radiation treatment plans, and help reduce the risk of radiation to adjacent normal tissues. However, while the introduction of PSMA PET will likely change behavior regarding earlier application of radiotherapy, the long-term impact of PSMA PET on patient outcomes is yet to be determined. The aim of the review is to give an overview of the use of PSMA-PET/CT imaging in the setting of radiation therapy for prostate cancer.
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Affiliation(s)
- Esther Mena
- Molecular Imaging Branch, NCI, NIH, Bethesda, MD.
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Spałek MJ, Teterycz P, Borkowska A, Poleszczuk J, Rutkowski P. Stereotactic radiotherapy for soft tissue and bone sarcomas: real-world evidence. Ther Adv Med Oncol 2022; 14:17588359211070646. [PMID: 35186124 PMCID: PMC8848098 DOI: 10.1177/17588359211070646] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 12/14/2021] [Indexed: 11/29/2022] Open
Abstract
Introduction: Selected patients with locally advanced or metastatic soft tissue and bone sarcomas (STBS) may benefit from intensive local treatment, such as stereotactic radiotherapy (SRT). This study aimed to summarize the utilization and outcomes of SRT in STBS and to identify predictive factors for progression and survival. Materials and methods: Consecutive patients with advanced STBS who underwent STBS in a sarcoma tertiary center were identified. We collected tumor- and treatment-related factors. Endpoints comprised time to local progression (TTLP), local progression-free survival (LPFS), time to progression, progression-free survival, and overall survival (OS). The Cox proportional-hazards model was used to identify prognostic factors. Results: We identified 141 patients who underwent 233 SRTs. Median follow-up was 21 months. Local and distant progression occurred after 19 and 163 SRTs, respectively. SRT for lung metastases was predictive for better TTLP and LPFS (hazard ratio, HR = 0.12, p = 0.007 and HR = 0.42, p = 0.002, respectively). Bone sarcoma (HR for TTLP = 3.18, p = 0.043; HR for LPFS = 1.99, p = 0.028) and lower administered dose (HR for TTLP = 0.98, p = 0.007; HR for LPFS = 0.99, p = 0.012) were predictive for worse TTLP and LPFS. SRT for oligometastases (HR = 0.46, p = 0.021) and lung metastases (HR = 0.55, p = 0.046) was predictive for better OS, whereas diagnosis of bone sarcoma (HR = 2.05, p = 0.029) was predictive for worse OS. Conclusion: SRT provides excellent local control in STBS patients without significant toxicity. Patients with oligometastatic disease, lung metastases, and soft tissue sarcomas benefit the most from SRT. The dose escalation moderately enhances local control; however, it does not translate into better survival.
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Affiliation(s)
- Mateusz Jacek Spałek
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Paweł Teterycz
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
- Department of Computational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Aneta Borkowska
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Jan Poleszczuk
- Department of Computational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
- Polish Academy of Sciences, Nalecz Institute of Biocybernetics and Biomedical Engineering, Warsaw, Poland
| | - Piotr Rutkowski
- Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
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Cozzi S, Botti A, Timon G, Blandino G, Najafi M, Manicone M, Bardoscia L, Ruggieri MP, Ciammella P, Iotti C. Prognostic factors, efficacy, and toxicity of involved-node stereotactic body radiation therapy for lymph node oligorecurrent prostate cancer : An investigation of 117 pelvic lymph nodes. Strahlenther Onkol 2021; 198:700-709. [PMID: 34757443 DOI: 10.1007/s00066-021-01871-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 10/17/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND The optimal radiotherapy regimen is not yet defined in the setting of oligorecurrent prostate cancer (oligorPC). There is evidence of high variability in treatment protocols among different centers worldwide, and no international consensus guidelines on treatment volumes, radiation schedules, and techniques. The purpose of the present retrospective study is to evaluate the efficacy and safety of involved-pelvic-node stereotactic body radiotherapy (SBRT) for oligorPC. MATERIALS AND METHODS Patients with pelvic node oligorPC following primary surgery, radical radiotherapy, or salvage radiotherapy for biochemical or local relapse of prostate cancer who underwent involved-node SBRT with biological effective dose (BED) > 100 Gy, with or without concurrent and adjuvant androgen deprivation therapy (ADT), were retrospectively evaluated. Biochemical progression-free survival (bPFS), distant progression-free survival (DPFS), overall survival (OS), possible prognostic factors, and toxicity outcomes were investigated. RESULTS From November 2012 to December 2019, 74 patients fitted the selection criteria. A total of 117 lesions were treated. Median follow-up was 31 months (range 6-89). Concurrent ADT was administered in 58.1% of patients. The 1‑year, 2‑year, and 3‑year DPFS was 77%, 37%, and 19%, respectively; the 1‑year, 2‑year, and 3‑year OS was 98%, 98%, and 95%, respectively. The presence of a single target lesion was associated with a statistically significant impact on OS. No in-field recurrence occurred. Patients who reached early prostate-specific antigen (PSA) nadir (< 3 months after SBRT) had a lower 3‑year survival (p = 0.004). The value of PSA nadir after SBRT and the time between primary treatment and SBRT had an impact on bPFS. Concomitant ADT was associated with improved DPFS. No acute or early late (> 6 months) genitourinary and gastrointestinal adverse events of any grade were reported, albeit with relatively short median follow-up. CONCLUSION SBRT is a safe and effective treatment for oligorPC, with a 100% local control rate in our series. It is not possible to clearly assess the opportunity to postpone ADT prescription in patients with two or more nodal metastases. The number of secondary lesions, time-to-nadir PSA, PSA nadir value, and the time interval between primary treatment and SBRT were identified as prognostic factors. Future prospective randomized studies are desirable to better understand the still open questions regarding the oligorecurrent prostate cancer state.
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Affiliation(s)
- Salvatore Cozzi
- Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
| | - Andrea Botti
- Medical Physics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Giorgia Timon
- Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Gladys Blandino
- Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Masoumeh Najafi
- Department of Radiation Oncology Shohadaye Haft-e-Tir Hospital, Iran University of Medical Science, Teheran, Iran
| | - Moana Manicone
- Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Lilia Bardoscia
- Radiation Oncology Unit, S. Luca Hospital, Healtcare Company Tuscany Nord Ovest, Lucca, Italy
| | - Maria Paola Ruggieri
- Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Patrizia Ciammella
- Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Cinzia Iotti
- Radiation Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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46
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Radiotherapy at oligoprogression for metastatic castration-resistant prostate cancer patients: a multi-institutional analysis. Radiol Med 2021; 127:108-116. [PMID: 34748151 DOI: 10.1007/s11547-021-01424-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 10/22/2021] [Indexed: 10/19/2022]
Abstract
PURPOSE To retrospectively estimate the impact of radiotherapy as a progression-directed therapy (PDT) in oligoprogressive metastatic castration-resistant prostate cancer (mCRPC) patients under androgen receptor-target therapy (ARTT). MATERIALS AND METHODS mCRPC patients are treated with PDT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events v4.0. Survival analysis was performed using the Kaplan-Meier method; univariate and multivariate analyses were performed. RESULTS Fifty-seven patients were analyzed. The median follow-up after PDT was 25.2 months (interquartile, 17.1-44.5). One-year NEST-free survival, r-PFS and OS were 49.8%, 50.4% and 82.1%, respectively. At multivariate analysis, polymetastatic condition at diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) (HR 2.82, p = 0.004) and PSA doubling time at diagnosis of mCRPC (HR 2.76, p = 0.006) were associated with NEST-free survival. The same variables were associated with r-PFS (HR 2.32, p = 0.021; HR 2.24, p = 0.021). One patient developed late grade ≥ 2 toxicity. CONCLUSION Our study shows that radiotherapy in oligoprogressive mCRPC is safe, is effective and seems to prolong the efficacy of ARTT in patients who otherwise would have gone systemic treatment switch, positively affecting disease progression. Prospective trials are needed.
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Cetin B, Wabl CA, Gumusay O. Optimal Treatment for Patients with Oligometastatic Prostate Cancer. Urol Int 2021; 106:217-226. [PMID: 34700315 DOI: 10.1159/000519386] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 08/13/2021] [Indexed: 11/19/2022]
Abstract
Oligometastatic prostate cancer (PCa) can be defined as cancer with a limited number of metastases, typically fewer than 5 lesions, and involves lesions contained within the axial versus the appendicular skeleton. Patients can present with de novo oligometastatic, oligorecurrent, or oligoprogressive PCa. Oligometastatic PCa patients demonstrate considerable improvements in survival outcomes, with a better prognosis than patients with extensive metastatic disease. However, the management of patients that present with nonsymptomatic oligometastatic PCa remains difficult. In the oligometastatic setting, the benefit of local therapies such as prostatectomy and radiotherapy on survival outcomes is an intriguing topic; however, their impact on oncological outcomes is still unknown.
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Affiliation(s)
- Bulent Cetin
- Division of Medical Oncology, Department of Internal Medicine, Suleyman Demirel University Faculty of Medicine, Isparta, Turkey
| | - Chiara A Wabl
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA
| | - Ozge Gumusay
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA
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48
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Patrikidou A, Zilli T, Baciarello G, Terisse S, Hamilou Z, Fizazi K. Should androgen deprivation therapy and other systemic treatments be used in men with prostate cancer and a rising PSA post-local treatments? Ther Adv Med Oncol 2021; 13:17588359211051870. [PMID: 34707693 PMCID: PMC8543684 DOI: 10.1177/17588359211051870] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 09/20/2021] [Indexed: 12/24/2022] Open
Abstract
Biochemical recurrence is an evolving space in prostate cancer, with increasing multidisciplinary involvement. Androgen deprivation therapy has shown proof of its value in complementing salvage radiotherapy in high-risk biochemical relapsing patients; ongoing trials aim to further refine this treatment combination. As systemic treatments, and notably next-generation androgen receptor targeted agents, have moved towards early hormone-sensitive and non-metastatic stages, the prostate specific antigen (PSA)-relapse disease stage will be undoubtedly challenged by future evidence from such ongoing clinical trials. With the use of modern imaging and newer molecular technologies, including integration of tumoral genomic profiling and liquid biopsies in risk stratification, a path towards a precision oncology-focused approach will become a reality to guide in the future decisions for patients with a diagnosis of biochemical recurrence.
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Affiliation(s)
- Anna Patrikidou
- Department of Medical Oncology, Gustave Roussy Institute, Paris Saclay University, 114 rue Edouard Vaillant, Villejuif, 94800, FranceUCL Cancer Institute & University College London Hospital, London, United Kingdom
| | - Thomas Zilli
- Department of Radiation Oncology, Geneva University Hospital and Faculty of Medicine, Geneva University, Geneva, Switzerland
| | | | - Safae Terisse
- Department of Medical Oncology, Saint Louis Hospital, Paris, France
| | - Zineb Hamilou
- Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada
| | - Karim Fizazi
- Department of Medical Oncology, Gustave Roussy Institute, Paris Saclay University, 114 rue Edouard Vaillant, Villejuif, 94800, France
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49
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Stereotactic body radiotherapy to lymph nodes in oligoprogressive castration-resistant prostate cancer patients: a post hoc analysis from two phase I clinical trials. Clin Exp Metastasis 2021; 38:519-526. [PMID: 34651242 DOI: 10.1007/s10585-021-10126-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 09/29/2021] [Indexed: 10/20/2022]
Abstract
The prognosis of prostate cancer (PC) is generally favorable but the incidence of metastases is relatively high after the treatment of the primary tumor, especially in high-risk patients. Fractionated stereotactic body radiotherapy (SBRT) or single fraction stereotactic body radiosurgery (SRS) are emerging treatment options in this setting. However, data on SBRT/SRS in patients with metastatic castration-resistant PC (mCRPC) are largely lacking, particularly in subjects with nodal lesions. Therefore, we evaluated outcomes and toxicity recorded in mCRPC patients with nodal oligoprogression. Patients included in this analysis had ≤ 5 metastatic sites without visceral lesions and underwent SBRT/SRS on nodal metastases. Thirty-eight patients carrying out 61 nodal metastases were analyzed. The median SRS dose was 20 Gy (range 12-24 Gy) and the most common schedule was 20 Gy (44.8%). The median SBRT dose was 45 Gy (range 20-50 Gy) and the most common regimen was 45 Gy in 5 fractions (37.9%). Thirty-seven patients (97.4%) showed only grade 0-1 acute toxicity while one patient reported grade 2 dysphagia. In terms of late toxicity, one grade 2 laryngeal, one grade 1 skin and one grade 1 gastrointestinal toxicities were recorded. Two-year actuarial local control (LC), distant progression-free survival, progression-free survival (PFS) and overall survival were 94.0, 47.2, 47.2, and 90.2%, respectively. Two-year next line systemic therapy-free survival (NEST-FS) was 67.7%. In conclusion, the efficacy in terms of LC of SBRT/SRS in patients with nodal metastases from PC was confirmed. Moreover, this analysis suggests the efficacy in terms of PFS and NEST-FS also in the setting of oligoprogressive PC. In fact, about one-third of patients were free from progressive disease and two-third of subjects did not require hormonal therapy switch or discontinuation three years after treatment.
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50
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Rogowski P, Trapp C, von Bestenbostel R, Eze C, Ganswindt U, Li M, Unterrainer M, Zacherl MJ, Ilhan H, Beyer L, Kretschmer A, Bartenstein P, Stief C, Belka C, Schmidt-Hegemann NS. Outcome after PSMA-PET/CT-based salvage radiotherapy for nodal recurrence after radical prostatectomy. Eur J Nucl Med Mol Imaging 2021; 49:1417-1428. [PMID: 34628521 PMCID: PMC8921036 DOI: 10.1007/s00259-021-05557-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 09/05/2021] [Indexed: 11/27/2022]
Abstract
Purpose Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. Methods A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method and uni- and multivariate analysis was performed. Results Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1–40.1) in patients with bcP and 1.4 ng/ml (range 0.3–5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60–70 Gy) was delivered to the prostatic fossa, 70 Gy (66–72 Gy) to the local recurrence, if present, 65.1 Gy (56–66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4–50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. Conclusions Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome.
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Affiliation(s)
- Paul Rogowski
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
| | - Christian Trapp
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Rieke von Bestenbostel
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Chukwuka Eze
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Ute Ganswindt
- Department of Radiation Oncology, University Hospital, Medical University Innsbruck, Innsbruck, Austria
| | - Minglun Li
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Marcus Unterrainer
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany.,Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Mathias J Zacherl
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Harun Ilhan
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Leonie Beyer
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | | | - Peter Bartenstein
- Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
| | - Christian Stief
- Department of Urology, University Hospital, LMU Munich, Munich, Germany
| | - Claus Belka
- Department of Radiation Oncology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.,German Cancer Consortium (DKTK), Munich, Germany
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