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Shafiee M, Soltani Fard E, Taghvimi S, Movahedpour A, Mousavi P, Rezaeijo SM, Khatami SH, Azadbakht O. "Nanoparticle-based sensitizers in prostate cancer treatment: Enhancing radiotherapy efficacy through innovative nanotechnology: Narrative review". Appl Radiat Isot 2025; 218:111671. [PMID: 39826201 DOI: 10.1016/j.apradiso.2025.111671] [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: 05/29/2024] [Revised: 01/04/2025] [Accepted: 01/07/2025] [Indexed: 01/22/2025]
Abstract
For men with localized prostate cancer, radiotherapy (RT) remains a common therapeutic option. Although radiotherapy has had significant success, it remains an intractable issue in promoting radiation damage to tumor tissue while reducing adverse effects on healthy tissue. Chemicals or pharmacological substances known as radiosensitizers can increase the killing effect on tumor cells by accelerating DNA damage and indirectly producing free radicals. Of all the approaches to improving RT management outcomes, metal nanoparticle-enhanced radiation for prostate cancer patient therapy is a unique strategy that has sparked scientific attention in the past decade. Most current data is based on targeted RT with gold nanoparticles, among the most studied materials. Nevertheless, several novel materials have also been employed in preclinical settings. This study assesses existing dosimetric data on prostate cancer tissue as well as the likely future influence on treatment options and patient outcomes since further research in a clinical setting is necessary.
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Affiliation(s)
- Mohsen Shafiee
- Department of Nursing, Abadan University of Medical Sciences, Abadan, Iran.
| | - Elahe Soltani Fard
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Sina Taghvimi
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
| | | | - Pegah Mousavi
- Molecular Medicine Research Center, Hormozgan Health Institude, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
| | - Seyed Masoud Rezaeijo
- Department of Medical Physics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Seyyed Hossein Khatami
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Oguic R, Grskovic A, Spanjol J, Mikolasevic I, Djordjevic G. CD44 Immunohistochemical Expression in Central and Peripheral Parts of Prostatic Adenocarcinoma: An Institutional Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2032. [PMID: 39768912 PMCID: PMC11728140 DOI: 10.3390/medicina60122032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 11/18/2024] [Accepted: 11/27/2024] [Indexed: 01/16/2025]
Abstract
Background and Objectives: Prostate cancer is one of the most commonly diagnosed cancers in the male population and the fifth leading cause of cancer death worldwide in men as of 2022. One of the potential biomarkers that can predict the progression of the disease is the transmembrane adhesion molecule CD44s. The aims of this study were to determine the expression of CD44s in prostate cancer in the central tumor mass and in the tumor periphery of the disease and to compare it with the clinicopathological parameters (PSA, Gleason score, surgical margins, and biochemical recurrence of the disease) in patients treated with radical prostatectomy. Materials and Methods: The research was randomized retrospectively during the period from 2001 to 2006. Tissue microarrays of 121 archival acinar prostate carcinoma samples were immunohistochemically evaluated for CD44s expression. The immunoexpression was determined semiquantitatively, taking into account the percentage (0 (0-5%), 1 (6-24%), 2 (26-75%), and 3 (76-100%) and intensity of the membranous staining of the tumor cells (0 absent; 1 weak at 400×; 2 intermediates at 100×; 3 strong at 40×) and calculated to obtain a final score (0-3 were regarded as negative; 4-6 were regarded as positive). Results: For statistical purposes, we divided the tumors into two categories: Gleason grade group 1 makes up 80.7% and grade group 2, which includes all the remaining Gleason grade groups (out of 2-5), accounts for 19.3% of the tumors. Grade group 1 had the highest incidence of score 4 (positive expression). There were statistically significantly more positive expressions in those tumors with negative prostatectomy margins (chi square: p = 0.001; Cramer V: 0.319). There was no correlation between CD44s expression and biochemical recurrence (p = 0.218), nor with the preoperative PSA values (p = 0.165). In the grade group 1 tumors, the CD44s immunoexpression and status of prostatectomy margin were statistically significantly related with negative margins (p = 0.028). An analysis of the expression of CD44s according to the localization in the central part of the tumor mass and on the periphery of the cancer in the group of tumors with a positive margin did not show a significant correlation because the sample was too small. Descriptively, it can be noted that the expression on the periphery was higher, and the central/peripheral expression ratio was higher in favor of the periphery. Conclusions: Our results provide insight into the possible value of CD44s expression for predicting the behavior of prostate tumors and the justification of therapy after a prostatectomy. Also hypothetically, they indicate a protective role of CD44s in a group of well-differentiated tumors at the periphery of the tumor mass. Therefore, it is useful to study the CD44s molecule further in this sense.
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Affiliation(s)
- Romano Oguic
- Department of Urology, University Hospital Rijeka, 51000 Rijeka, Croatia; (R.O.); (A.G.); (J.S.)
| | - Antun Grskovic
- Department of Urology, University Hospital Rijeka, 51000 Rijeka, Croatia; (R.O.); (A.G.); (J.S.)
| | - Josip Spanjol
- Department of Urology, University Hospital Rijeka, 51000 Rijeka, Croatia; (R.O.); (A.G.); (J.S.)
| | - Ivana Mikolasevic
- Clinical Institute of Oncology and Radiotherapy, University Hospital Centre Rijeka, 51000 Rijeka, Croatia;
| | - Gordana Djordjevic
- Department of Pathology and Cytology, University Hospital Center Rijeka, 51000 Rijeka, Croatia
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Rosin RD, Haynes A, Kidd M, Drozdov I, Modlin I, Halim A. Evaluation of a multigenomic liquid biopsy (PROSTest) for prostate cancer detection and follow-up in a Caribbean population. Cancer Epidemiol 2024; 92:102642. [PMID: 39121520 DOI: 10.1016/j.canep.2024.102642] [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: 05/29/2024] [Revised: 07/19/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024]
Abstract
INTRODUCTION The PROSTest is a novel machine learning-based liquid biopsy assay that functions as a diagnostic and prognostic tool in prostate cancer (PCa). The algorithm outcome (scored 0-100) has a cutoff of >50 to indicate PCa. In this study, we evaluated the screening utility of the test in comparison with the commonly used PSA test. MATERIALS AND METHODS 509 men (median age: 62 [40-88]), predominantly Afro-Caribbean (n=449, 88.2 %) were enrolled in this study at a referral centre for prostatic cancer screening and management. These included 417 symptomatic patients with urinary tract (UT) problems, of which 12 were diagnosed with PCa, 53 with benign prostatic hyperplasia (BPH) and 352 were free from prostatic diseases, prior to PROSTest (Cohort 1). The remaining 92 of the 509, with relatively young age (median 49 and range 40-75 years) were screened with the PROSTest first and included 28 with UT symptoms and 64 asymptomatic but with a family history of cancer (Cohort 2). PROSTest and PSA was performed on all subjects. RESULTS In Cohort 1, the PROSTest was positive in 11 (91.7 %) PCa, 9 (17.0 %) of BPH, and 29 (8.2 %) of subject with UT symptoms but no disease. In Cohort 2, PROSTest was positive in 4 of 28 (14.3 %) symptomatic patients and in 5 of 64 (7.8 %) asymptomatic subjects. A total of 111 individuals (from both cohorts) were identified as "at risk" (PSA >4 ng/mL). Sixteen of 111 (14.4 %) were PROSTest-positive. Thirty-nine percent (43/111) have completed a 1-year follow-up. Of the 43 with elevated PSA, 2 out of 2 (100 %) who were also PROSTest-positive, were diagnosed with PCa. CONCLUSION PROSTest is a more sensitive and specific biomarker than PSA in the diagnosis and, potentially, screening for PCa. The seemingly false positive PROSTest results in BPH or symptomatic UT require a longer follow-up of these patients.
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Affiliation(s)
- R David Rosin
- University of the West Indies Cave Hill Campus, Barbados; The Barbados Cancer Society, Barbados.
| | - Amelia Haynes
- University of the West Indies Cave Hill Campus, Barbados
| | - Mark Kidd
- Wren Laboratories, Branford, CT, USA
| | | | - Irvin Modlin
- Yale University School of Medicine, New Haven, CT, USA
| | - Abdel Halim
- University of the West Indies Cave Hill Campus, Barbados
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Chen Y, Lan T. N-terminal domain of androgen receptor is a major therapeutic barrier and potential pharmacological target for treating castration resistant prostate cancer: a comprehensive review. Front Pharmacol 2024; 15:1451957. [PMID: 39359255 PMCID: PMC11444995 DOI: 10.3389/fphar.2024.1451957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/09/2024] [Indexed: 10/04/2024] Open
Abstract
The incidence rate of prostate cancer (PCa) has risen by 3% per year from 2014 through 2019 in the United States. An estimated 34,700 people will die from PCa in 2023, corresponding to 95 deaths per day. Castration resistant prostate cancer (CRPC) is the leading cause of deaths among men with PCa. Androgen receptor (AR) plays a critical role in the development of CRPC. N-terminal domain (NTD) is the essential functional domain for AR transcriptional activation, in which modular activation function-1 (AF-1) is important for gene regulation and protein interactions. Over last 2 decades drug discovery against NTD has attracted interest for CRPC treatment. However, NTD is an intrinsically disordered domain without stable three-dimensional structure, which has so far hampered the development of drugs targeting this highly dynamic structure. Employing high throughput cell-based assays, small-molecule NTD inhibitors exhibit a variety of unexpected properties, ranging from specific binding to NTD, blocking AR transactivation, and suppressing oncogenic proliferation, which prompts its evaluation in clinical trials. Furthermore, molecular dynamics simulations reveal that compounds can induce the formation of collapsed helical states. Nevertheless, our knowledge of NTD structure has been limited to the primary sequence of amino acid chain and a few secondary structure motif, acting as a barrier for computational and pharmaceutical analysis to decipher dynamic conformation and drug-target interaction. In this review, we provide an overview on the sequence-structure-function relationships of NTD, including the polymorphism of mono-amino acid repeats, functional elements for transcription regulation, and modeled tertiary structure of NTD. Moreover, we summarize the activities and therapeutic potential of current NTD-targeting inhibitors and outline different experimental methods contributing to screening novel compounds. Finally, we discuss current directions for structure-based drug design and potential breakthroughs for exploring pharmacological motifs and pockets in NTD, which could contribute to the discovery of new NTD inhibitors.
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Affiliation(s)
- Ye Chen
- Department of Anesthesiology, Xi’an International Medical Center Hospital Affiliated To Northwest University, Xi’an, Shaanxi, China
| | - Tian Lan
- Department of Urology, Xi’an International Medical Center Hospital Affiliated To Northwest University, Xi’an, Shaanxi, China
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Wang J, Zhang X, Xing J, Gao L, Lu H. Nanomedicines in diagnosis and treatment of prostate cancers: an updated review. Front Bioeng Biotechnol 2024; 12:1444201. [PMID: 39318666 PMCID: PMC11420853 DOI: 10.3389/fbioe.2024.1444201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 08/05/2024] [Indexed: 09/26/2024] Open
Abstract
Prostate cancer (PC) is the third most common male cancer in the world, which occurs due to various mutations leading to the loss of chromatin structure. There are multiple treatments for this type of cancer, of which chemotherapy is one of the most important. Sometimes, a combination of different treatments, such as chemotherapy, radiotherapy, and surgery, are used to prevent tumor recurrence. Among other treatments, androgen deprivation therapy (ADT) can be mentioned, which has had promising results. One of the drawbacks of chemotherapy and ADT treatments is that they are not targeted to the tumor tissue. For this reason, their use can cause extensive side effects. Treatments based on nanomaterials, known as nanomedicine, have attracted much attention today. Nanoparticles (NPs) are one of the main branches of nanomedicine, and they can be made of different materials such as polymer, metal, and carbon, each of which has distinct characteristics. In addition to NPs, nanovesicles (NVs) also have therapeutic applications in PC. In treating PC, synthetic NVs (liposomes, micelles, and nanobubbles) or produced from cells (exosomes) can be used. In addition to the role that NPs and NVs have in treating PC, due to being targeted, they can be used to diagnose PC and check the treatment process. Knowing the characteristics of nanomedicine-based treatments can help design new treatments and improve researchers' understanding of tumor biology and its rapid diagnosis. In this study, we will discuss conventional and nanomedicine-based treatments. The results of these studies show that the use of NPs and NVs in combination with conventional treatments has higher efficacy in tumor treatment than the individual use of each of them.
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Affiliation(s)
- Jiajia Wang
- Department of Oncology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China
| | - Xuan Zhang
- Department of Urology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China
| | - Jiazhen Xing
- Department of Urology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China
| | - Lijian Gao
- Department of Urology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China
| | - Hua Lu
- Department of Urology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China
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Solyanik O, Chaloupka M, Clevert DA, Schmidt VF, Ingenerf M, Kazmierczak P, Stief CG, Ricke J, Apfelbeck M. Prospective close monitoring of the effect of vascular-targeted photodynamic therapy and high intensity focused ultrasound of localized prostate cancer by multiparametric magnetic resonance imaging. World J Urol 2024; 42:462. [PMID: 39088086 DOI: 10.1007/s00345-024-05143-6] [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: 09/15/2023] [Accepted: 06/21/2024] [Indexed: 08/02/2024] Open
Abstract
PURPOSE The aim of this study is to describe the anatomical and functional changes observed in multiparametric magnetic resonance imaging (mpMRI) during follow-up after focal therapy (FT) for localized prostate cancer (PCa). MATERIALS AND METHODS In this prospective study, we analyzed pre- and postoperatively acquired mpMRI of 10 patients after FT (7 days; 3, 6, 9, 12 months). 7/10 (70%) patients underwent vascular-targeted photodynamic therapy (VTP). 3/10 (30%) patients underwent high-intensity focused ultrasound (HIFU). MpMR image analysis was performed using a semi-automatic software for segmentation of the prostate gland (PG) and tumor zones. Signal intensities (SI) of T2-weighted (T2w), T1-weighted (T1w),diffusion-weighted (DWI) and dynamic contrast-enhanced (DCE) images as well as volumes of the prostate gland (PGV) and tumor volumes (TV) were evaluated at each time point. RESULTS The results showed a significant increase of PGV 7 days after FT (p = 0.042) and a significant reduction of PGV between 7 days and 6, 9 and 12 months after FT (p < 0.001). The TV increased significantly 7 days after FT (p < 0.001) and decreased significantly between 7 days and 12 months after FT (p < 0.001). There was a significant increase in SI of the ADC in the ablation zone after 6, 9 and 12 months after FT (p < 0.001). 1/9 patients (11%) had recurrent tumor on rebiopsy characterized as a a small focal lesion on mpMRI with strong diffusion restriction (low SI on ADC map and high SI on b-value DWI). CONCLUSION MpMRI is able to represent morphologic changes of the ablated zone after FT and might be helpful to detect recurrent tumor.
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Affiliation(s)
| | - Michael Chaloupka
- Department of Urology, LMU Klinikum, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Dirk-André Clevert
- Department of Radiology, LMU Klinikum, Ludwig-Maximilians-University Munich, Germany, Munich
| | - Vanessa F Schmidt
- Department of Radiology, LMU Klinikum, Ludwig-Maximilians-University Munich, Germany, Munich
| | - Maria Ingenerf
- Department of Radiology, LMU Klinikum, Ludwig-Maximilians-University Munich, Germany, Munich
| | - Philipp Kazmierczak
- Department of Radiology, LMU Klinikum, Ludwig-Maximilians-University Munich, Germany, Munich
| | - Christian G Stief
- Department of Urology, LMU Klinikum, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Jens Ricke
- Department of Radiology, LMU Klinikum, Ludwig-Maximilians-University Munich, Germany, Munich
| | - Maria Apfelbeck
- Department of Urology, LMU Klinikum, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany.
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Gonzales J, Adilbay D, de Souza Franca PD, Artschwager R, Chow CY, Viray T, Johnson DS, Jiang Y, Patel SG, Ganly I, Schroeder CI, Lewis JS, King GF, Reiner T, Pillarsetty N. Na V1.7 targeted fluorescence imaging agents for nerve identification during intraoperative procedures. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.04.06.588368. [PMID: 38617358 PMCID: PMC11014580 DOI: 10.1101/2024.04.06.588368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/16/2024]
Abstract
Surgeries and trauma result in traumatic and iatrogenic nerve damage that can result in a debilitating condition that approximately affects 189 million individuals worldwide. The risk of nerve injury during oncologic surgery is increased due to tumors displacing normal nerve location, blood turbidity, and past surgical procedures, which complicate even an experienced surgeon's ability to precisely locate vital nerves. Unfortunately, there is a glaring absence of contrast agents to assist surgeons in safeguarding vital nerves. To address this unmet clinical need, we leveraged the abundant expression of the voltage-gated sodium channel 1.7 (NaV1.7) as an intraoperative marker to access peripheral nerves in vivo, and visualized nerves for surgical guidance using a fluorescently-tagged version of a potent NaV1.7-targeted peptide, Tsp1a, derived from a Peruvian tarantula. We characterized the expression of NaV1.7 in sensory and motor peripheral nerves across mouse, primate, and human specimens and demonstrated universal expression. We synthesized and characterized a total of 10 fluorescently labeled Tsp1a-peptide conjugates to delineate nerves. We tested the ability of these peptide-conjugates to specifically accumulate in mouse nerves with a high signal-to-noise ratio in vivo. Using the best-performing candidate, Tsp1a-IR800, we performed thyroidectomies in non-human primates and demonstrated successful demarcation of the recurrent laryngeal and vagus nerves, which are commonly subjected to irreversible damage. The ability of Tsp1a to enhance nerve contrast during surgery provides opportunities to minimize nerve damage and revolutionize standards of care across various surgical specialties.
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Affiliation(s)
- Junior Gonzales
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Dauren Adilbay
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Paula Demetrio de Souza Franca
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
- Department of Otorhinolaryngology and Head and Neck Surgery, Federal University of São Paulo, SP, Brazil
| | - Raik Artschwager
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Chun Yuen Chow
- Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia
- Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Research, The University of Queensland, St Lucia, Queensland 4072, Australia
| | - Tara Viray
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Delissa S. Johnson
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
| | - Yan Jiang
- Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia
| | - Snehal G. Patel
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
- Department of Otorhinolaryngology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA
| | - Ian Ganly
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
- Department of Otorhinolaryngology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA
| | - Christina I. Schroeder
- Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia
| | - Jason S. Lewis
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
- Department of Pharmacology, Weill-Cornell Medical College, New York, New York, 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA
- Department of Radiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA
| | - Glenn F. King
- Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia
- Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Research, The University of Queensland, St Lucia, Queensland 4072, Australia
| | - Thomas Reiner
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
- Department of Pharmacology, Weill-Cornell Medical College, New York, New York, 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA
- Department of Radiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA
| | - Nagavarakishore Pillarsetty
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10065, USA
- Department of Pharmacology, Weill-Cornell Medical College, New York, New York, 10065, USA
- Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA
- Department of Radiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York, 10065, USA
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Sood A, Grauer R, Diaz-Insua M, Tewari AK, Hemal AK, Shrivastava A, Peabody JO, Jeong W, Abdollah F, Rudzinski JK, Andrews JR, Gorin MA, Bhandari M, Menon M. 15-year biochemical failure, metastasis, salvage therapy, and cancer-specific and overall survival rates in men treated with robotic radical prostatectomy for PSA-screen detected prostate cancer. Prostate Cancer Prostatic Dis 2023; 26:778-786. [PMID: 37142635 DOI: 10.1038/s41391-023-00674-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 04/14/2023] [Accepted: 04/20/2023] [Indexed: 05/06/2023]
Abstract
BACKGROUND An informed decision regarding a treatment option requires data on its long-term efficacy and side-effect profile. While the side-effects of robotic radical prostatectomy have been well-quantified, the data on its long-term efficacy are lacking. We here provide 15-year oncological outcomes of clinically-localized prostate cancer (CLPCa) patients treated with robot-assisted laparoscopic prostatectomy (RALP). METHODS We treated 1,807 men with CLPCa with RALP between 2001 and 2005 and prospectively collected follow-up data through 2020. We examined the rates of biochemical failure (BCF), metastatic progression, secondary therapy use, PCa-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and competing-risk cumulative incidence methods as appropriate. RESULTS The median follow-up was 14.1 years. Six hundred eight and 312 men had D'Amico intermediate- and high-risk disease, respectively. Overall, the 15-year rates of BCF, metastasis, secondary therapy use, PCSM, and OS were 28.1%, 4.0%, 16.3%, 2.5%, and 82.1%, respectively. The rates of oncologic failure increased with increasing D'Amico (preoperative) and Diaz (postoperative) risk scores - BCF, metastasis, and PCSM rates in D'Amico low-, intermediate-, and high-risk groups at 15-years were 15.2%, 38.3%, and 44.1% [BCF], 1.1%, 4.1%, and 13.0% [metastasis], and 0.5%, 3.4%, and 6.6% [PCSM], respectively, and in Diaz risk groups 1, 2, 3, 4, and 5 were 5.5%, 20.6%, 41.8%, 66.9%, and 89.2% [BCF], 0%, 0.5%, 3.2%, 20.5%, and 60.0% [metastasis], and 0%, 0.8%, 0.6%, 13.5%, and 37.5% [PCSM], respectively. The OS rates in D'Amico low-to-high and Diaz 1-to-5 risk groups at 15-years were 85.9%, 78.6%, and 75.2%, and 89.4%, 83.2%, 80.6%, 67.2%, and 23.4%, respectively. CONCLUSIONS Men diagnosed with clinically-localized prostate cancer in the contemporaneous PSA-screening era and treated with RALP achieve durable long-term oncological control. The data reported here (in a risk-stratified manner) represent the longest follow-up after robotic radical prostatectomy, and as such, should be of value when counseling patients regarding expected oncologic outcomes from RALP.
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Affiliation(s)
- Akshay Sood
- VCORE - Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation, Henry Ford Hospital, Detroit, MI, USA.
- Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA.
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- Department of Urology, The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
| | - Ralph Grauer
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Mireya Diaz-Insua
- VCORE - Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation, Henry Ford Hospital, Detroit, MI, USA
| | - Ashutosh K Tewari
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ashok K Hemal
- Department of Urology, Wake Forest University, Winston-Salem, NC, USA
| | | | - James O Peabody
- Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA
| | - Wooju Jeong
- Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA
| | - Firas Abdollah
- VCORE - Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation, Henry Ford Hospital, Detroit, MI, USA
- Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA
| | - Jan K Rudzinski
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jack R Andrews
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael A Gorin
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - Mani Menon
- VCORE - Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation, Henry Ford Hospital, Detroit, MI, USA
- Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA
- Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Chew L, Chang C, Simhan J. Climacturia: what treatment options do we offer to those with and without concomitant erectile dysfunction? Int J Impot Res 2023; 35:634-638. [PMID: 37161059 DOI: 10.1038/s41443-023-00714-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 04/18/2023] [Accepted: 04/26/2023] [Indexed: 05/11/2023]
Abstract
Radical prostatectomy for prostate cancer carries many sequelae, including climacturia, which is not commonly discussed and often under-recognized. To better understand treatment options for incontinence and climacturia, as well as those at time of penile implantation surgery, we completed a comprehensive literature review to identify nonoperative and operative treatments for patients with climacturia alone and those with concomitant climacturia and erectile dysfunction. Nonoperative interventions include behavioral modifications, physical therapy, and tension loops. Operative interventions include the artificial urinary sphincter, male urethral slings, Mini-Jupette sling, and a periurethral prosthesis. We also explore options that can be offered to patients who are also in need of penile prosthesis for concomitant erectile dysfunction. Contemporary work suggests that synchronous implantation of certain devices to treat both climacturia and erectile dysfunction can be done with proven safety and efficacy.
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Affiliation(s)
- Lauren Chew
- Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Chrystal Chang
- Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Jay Simhan
- Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA.
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10
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Han JH, Herlemann A, Washington SL, Lonergan PE, Carroll PR, Cooperberg MR, Jeong CW. Observation, Radiotherapy, or Radical Prostatectomy for Localized Prostate Cancer: Survival Analysis in the United States. World J Mens Health 2023; 41:940-950. [PMID: 37118954 PMCID: PMC10523124 DOI: 10.5534/wjmh.220151] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 10/13/2022] [Accepted: 01/01/2023] [Indexed: 03/18/2023] Open
Abstract
PURPOSE Contemporary treatment strategies for localized prostate cancer (PCa) have been evolved over time. However, there is little data regarding survival outcomes based on initial treatment by risk group in this new era. This study aims to evaluate survival outcomes among men who underwent observation, radiotherapy, or radical prostatectomy for localized PCa using a population-based cohort. MATERIALS AND METHODS The Surveillance, Epidemiology, and End Results (SEER) prostate with watchful waiting dataset (2010-2016) was used. We included men diagnosed with localized PCa and clinical stage T1c-2cN0M0. Other inclusion criteria were age 50-79 years, prostate-specific antigen (PSA) ≤50 ng/mL, and initial treatment with observation (active surveillance/watchful waiting), radiotherapy, or radical prostatectomy. PCa risk was assessed using the D'Amico classification. The primary endpoint was overall survival. Secondary endpoints included PCa-specific survival. Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression and competing risk analysis were performed to assess outcomes. RESULTS After IPTW-adjusting, pseudo-population comprised 521,656 men (observation: 170,428, radiotherapy: 175,628, radical prostatectomy: 175,600) at a median 36.5 month follow-up. Observation demonstrated the lowest 5-year overall survival rate (91.6%) after IPTW-adjusting in comparison to radiotherapy (92.4%) and radical prostatectomy (96.1%, p<0.001). Men who underwent radical prostatectomy had the lowest cumulative PCa-specific and all-cause mortality (p<0.001). Compared to observation, radiotherapy (sub-distribution hazard ratio [sHR], 0.89; 95% CI, 0.81-0.97; p=0.012) and radical prostatectomy (sHR, 0.46; 95% CI, 0.41-0.52; p<.001) had a lower risk of PCa-specific mortality in competing risk analysis after adjustment for all other factors and other-cause death. CONCLUSIONS Intermediate-term mortality risk in men with localized PCa were lower with active treatments compared to observation-especially for intermediate- and high-risk disease. However, observation represents a safe management strategy in men within the low-risk group.
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Affiliation(s)
- Jang Hee Han
- Department of Urology, Seoul National University Hospital, Seoul, Korea
| | - Annika Herlemann
- Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
- Department of Urology, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Samuel L Washington
- Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
- Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA
| | - Peter E Lonergan
- Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
- Department of Urology, St. James's Hospital, Dublin, Ireland
- Department of Surgery, Trinity College, Dublin, Ireland
| | - Peter R Carroll
- Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
| | - Matthew R Cooperberg
- Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
- Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA
| | - Chang Wook Jeong
- Department of Urology, Seoul National University Hospital, Seoul, Korea
- Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
- Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
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11
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Sælen MG, Hjelle LV, Aarsæther E, Knutsen T, Andersen S, Bentzen AG, Richardsen E, Fosså SD, Haugnes HS. Patient-reported outcomes after curative treatment for prostate cancer with prostatectomy, primary radiotherapy or salvage radiotherapy. Acta Oncol 2023; 62:657-665. [PMID: 37353983 DOI: 10.1080/0284186x.2023.2224051] [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: 02/14/2023] [Accepted: 05/29/2023] [Indexed: 06/25/2023]
Abstract
BACKGROUND Trials reporting adverse health outcomes (AHOs) in terms of patient-reported outcome measures (PROMs) after contemporary curative treatment of prostate cancer (PC) are hampered by study heterogeneity and lack of new treatment techniques. Particularly, the evidence regarding toxicities after radiotherapy (RT) with the volumetric arc therapy (VMAT) technique is limited, and comparisons between men treated with surgery, primary radiotherapy (PRT) and salvage radiotherapy (SRT) are lacking. The aim of the study was to evaluate change in PROMs 3 months after treatment with robotic-assisted laparoscopic prostatectomy (RALP), PRT and SRT administered with VMAT. MATERIAL AND METHODS A prospective cohort study of men with PC who received curative treatment at the University Hospital of North Norway between 2012 and 2017 for RALP and between 2016 and 2021 for radiotherapy was conducted. A cohort of 787 men were included; 406 men treated with RALP, 265 received PRT and 116 received SRT. Patients completed the validated PROM instrument EPIC-26 before (pre-treatment) and 3 months after treatment. EPIC-26 domain summary scores (DSSs) were analysed, and changes from pre-treatment to 3 months reported. Changes were deemed clinically relevant if exceeding validated minimally clinically important differences (MCIDs). RESULTS Men treated with RALP reported clinically relevant declining urinary incontinence DSS (-41.7 (SD 30.7)) and sexual DSS (-46.1 (SD 30.2)). Men who received PRT reported worsened urinary irritative DSS (-5.2 (SD 19.6)), bowel DSS (-8.2 (SD 15.1)) and hormonal DSS (-9.6 (SD 18.2)). Men treated with SRT experienced worsened urinary incontinence DSS (-7.3 (SD 18.2)), urinary irritative DSS (-7.5 (SD 14.0)), bowel DSS (-12.5 (SD 16.1)), sexual DSS (-14.9 (SD 18.9)) and hormonal DSS (-23.8 (SD 20.9)). CONCLUSION AHOs 3 months after contemporary curative treatment for PC varied according to treatment modality and worsened in all treatment groups, although most in SRT.
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Affiliation(s)
- Marie G Sælen
- Department of Oncology, University Hospital of North Norway, Tromsø, Norway
| | - Line V Hjelle
- Department of Oncology, University Hospital of North Norway, Tromsø, Norway
| | - Erling Aarsæther
- Department of Urology, University Hospital of North Norway, Tromsø, Norway
| | - Tore Knutsen
- Department of Urology, University Hospital of North Norway, Tromsø, Norway
- Department of Clinical Medicine, UIT The Artic University, Tromsø, Norway
| | - Sigve Andersen
- Department of Oncology, University Hospital of North Norway, Tromsø, Norway
- Department of Clinical Medicine, UIT The Artic University, Tromsø, Norway
| | - Anne G Bentzen
- Department of Oncology, University Hospital of North Norway, Tromsø, Norway
| | - Elin Richardsen
- Department of Pathology, University Hospital of North Norway, Tromsø, Norway
| | - Sophie D Fosså
- Division of Cancer Medicine and Radiotherapy, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Hege S Haugnes
- Department of Oncology, University Hospital of North Norway, Tromsø, Norway
- Department of Clinical Medicine, UIT The Artic University, Tromsø, Norway
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12
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Rao Bommi J, Kummari S, Lakavath K, Sukumaran RA, Panicker LR, Marty JL, Yugender Goud K. Recent Trends in Biosensing and Diagnostic Methods for Novel Cancer Biomarkers. BIOSENSORS 2023; 13:398. [PMID: 36979610 PMCID: PMC10046866 DOI: 10.3390/bios13030398] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/13/2023] [Accepted: 03/15/2023] [Indexed: 06/18/2023]
Abstract
Cancer is one of the major public health issues in the world. It has become the second leading cause of death, with approximately 75% of cancer deaths transpiring in low- or middle-income countries. It causes a heavy global economic cost estimated at more than a trillion dollars per year. The most common cancers are breast, colon, rectum, prostate, and lung cancers. Many of these cancers can be treated effectively and cured if detected at the primary stage. Nowadays, around 50% of cancers are detected at late stages, leading to serious health complications and death. Early diagnosis of cancer diseases substantially increases the efficient treatment and high chances of survival. Biosensors are one of the potential screening methodologies useful in the early screening of cancer biomarkers. This review summarizes the recent findings about novel cancer biomarkers and their advantages over traditional biomarkers, and novel biosensing and diagnostic methods for them; thus, this review may be helpful in the early recognition and monitoring of treatment response of various human cancers.
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Affiliation(s)
| | - Shekher Kummari
- Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad 678 557, Kerala, India
| | - Kavitha Lakavath
- Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad 678 557, Kerala, India
| | - Reshmi A. Sukumaran
- Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad 678 557, Kerala, India
| | - Lakshmi R. Panicker
- Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad 678 557, Kerala, India
| | - Jean Louis Marty
- Université de Perpignan Via Domitia, 52 Avenue Paul Alduy, 66860 Perpignan, France
| | - Kotagiri Yugender Goud
- Department of Chemistry, Indian Institute of Technology Palakkad, Palakkad 678 557, Kerala, India
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13
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Oh M, McBride A, Bhattacharjee S, Slack M, Jeter J, Abraham I. Economic value of knowing BRCA status: BRCA testing for prostate cancer prevention and optimal treatment. Expert Rev Pharmacoecon Outcomes Res 2023; 23:297-307. [PMID: 36649640 DOI: 10.1080/14737167.2023.2169137] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND We aimed to estimate the incremental lifetime effects, costs, and net-monetary-benefit (NMB) of knowing BRCA information by testing of patients with low-risk localized prostate cancer (PCa) in the US and guiding subsequent screening and treatment, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1)'with BRCA information' and (2)'without BRCA information.' We also estimated the expected value of perfect information. METHODS The incremental NMB (INMB) quantified the monetized benefit per person of knowing BRCA status. The net-monetized-value of knowing BRCA information was estimated by multiplying the INMB with the eligible population. RESULTS The INMBs of knowing BRCA information were $43,357 (payer) and $43,487 (society). in payer and societal perspectives, respectively. Escalated to the eligible patients in 2020, knowing BRCA status resulted in net monetized lifetime value of $1.7 billion (payer and society) for the 2020 cohort; and yielded accumulated net-monetized-value of $28.0 billion (payer) and $28.1 billion (society) over 16 yearly cohorts of eligible PCa patients. CONCLUSIONS The economic value of knowing BRCA status for all low-risk localized PCa patients in the US provides short-term and long-term evidence for BRCA testing to screen early and optimize treatment.
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Affiliation(s)
- Mok Oh
- College of Pharmacy, University of Arizona, Tucson, AZ, USA
| | - Ali McBride
- Cancer Center - North Campus, The University of Arizona, Tucson, AZ, USA
| | | | - Marion Slack
- College of Pharmacy, University of Arizona, Tucson, AZ, USA.,Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, University of Arizona, Tucson, AZ, USA
| | - Joanne Jeter
- Health Huntsman Cancer Institute, University of Utah
| | - Ivo Abraham
- Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, University of Arizona, Tucson, AZ, USA
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14
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Urinary Continence Recovery after Robotic Radical Prostatectomy without Anterior or Posterior Reconstruction: Experience from a Tertiary Referral Center. J Clin Med 2023; 12:jcm12041358. [PMID: 36835893 PMCID: PMC9962972 DOI: 10.3390/jcm12041358] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 01/25/2023] [Accepted: 02/07/2023] [Indexed: 02/11/2023] Open
Abstract
BACKGROUND The aim of our study is to evaluate the prevalence and predictive factors of short- (30 d) and mid-term continence in a contemporary cohort of patients treated with robotic-assisted laparoscopic prostatectomy (RALP) without any posterior or anterior reconstruction at our referral academic center. METHODS Data from patients undergoing RALP between January 2017 and March 2021 were prospectively collected. RALP was performed by three highly experienced surgeons following the principles of the Montsouris technique, with a bladder-neck-sparing intent and maximal preservation of the membranous urethra (if oncologically safe) without any anterior/posterior reconstruction. (Self-assessed urinary incontinence (UI) was defined as the need of one or more pads per die (excluding the need for a safety pad/die. Univariable and multivariable logistic regression analysis was used to assess the independent predictors of early incontinence among routinely collected patient- and tumor-related variables). RESULTS A total of 925 patients were included; of these, 353 underwent RALP (38.2%) without nerve-sparing intent. The median patient age and BMI were 68 years (IQR 63-72) and 26 (IQR 24.0-28.0), respectively. Overall, 159 patients (17.2%) reported early (30 d) incontinence. In multivariable analysis adjusting for patient- and tumor-related features, a non-nerve-sparing procedure (OR: 1.57 [95% CI: 1.03-2.59], p = 0.035) was independently associated with the risk of urinary incontinence in the short-term period, while the absence of cardiovascular diseases before surgery (OR: 0.46 [95% CI: 0.320.67], p ≤ 0.01) was a protective factor for this outcome. At a median follow-up of 17 months (IQR 10-24), 94.5% of patients reported to be continent. CONCLUSIONS In experienced hands, most patients fully recover urinary continence after RALP at mid-term follow-up. On the contrary, the proportion of patients who reported early incontinence in our series was modest but not negligible. The implementation of surgical techniques advocating anterior and/or posterior fascial reconstruction might improve the early continence rate in candidates for RALP.
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15
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Asimakopoulos AD, Annino F, Colalillo G, Gaston R, Piechaud T, Mauriello A, Anceschi U, Borri F. "Urethral-Sparing" Robotic Radical Prostatectomy: Critical Appraisal of the Safety of the Technique Based on the Histologic Characteristics of the Prostatic Urethra. Curr Oncol 2023; 30:1065-1076. [PMID: 36661731 PMCID: PMC9857678 DOI: 10.3390/curroncol30010082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/07/2023] [Accepted: 01/09/2023] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND The prostatic urethra (PU) is conventionally resected during robot-assisted radical prostatectomy (RALP). Recent studies demonstrated the feasibility of the extended PU preservation (EPUP). AIMS To describe the histologic features of the PU. METHODS The PU was evaluated using cystoprostatectomy and RALP specimens. Cases of PU infiltration by prostate cancer or distortion by benign hyperplastic nodules were excluded. The thickness of the chorion and distance between the urothelium and prostate glands were measured. Prostate-specific antigen expression in the PU epithelium was evaluated with immunohistochemistry. Descriptive statistics were used. RESULTS Six specimens of PU were examined. Histologically, the following layers of the PU were observed: (1) urothelium with basal membrane, (2) chorion, and (3) prostatic peri-urethral fibromuscular tissue. The chorion measures between 0.2 and 0.4 mm. There is not a distinct urethral muscle layer, but rather muscular fibers that originate near the prostatic stroma and are distributed around the PU. This muscular tissue appears to be mainly represented in the basal and apical urethra, but not in the middle urethra. The mean distance between the chorion and prostatic glands is 1.74 mm, with significant differences between base of the prostate, middle urethral portion, and apex (2.5 vs. 1.49 vs. 1.23 mm, respectively). PSA-expressing cells are abundant in the PU epithelium, coexisting with urothelial cells. CONCLUSIONS The exiguity of thickness of the PU chorion, short distance from glandular tissue, and coexistence of PSA-expressing cells in the epithelium raise important concerns about the oncologic safety of EPUP.
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Affiliation(s)
- Anastasios D. Asimakopoulos
- Urology Unit, Fondazione PTV Policlinico Tor Vergata, 00133 Rome, Italy
- Urology Unit, Azienda USL Toscana Sud-Est, San Donato Hospital, 52100 Arezzo, Italy
| | - Filippo Annino
- Urology Unit, Azienda USL Toscana Sud-Est, San Donato Hospital, 52100 Arezzo, Italy
| | - Gaia Colalillo
- Urology Unit, Fondazione PTV Policlinico Tor Vergata, 00133 Rome, Italy
| | - Richard Gaston
- Unit of Urology, Clinique Saint-Augustin, 33074 Bordeaux, France
| | - Thierry Piechaud
- Unit of Urology, Clinique Saint-Augustin, 33074 Bordeaux, France
| | - Alessandro Mauriello
- Pathology, Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy
| | - Umberto Anceschi
- Department of Urology, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| | - Filippo Borri
- Anatomic Pathology, Azienda USL Toscana Sud-Est, San Donato Hospital, 52100 Arezzo, Italy
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Sieswerda M, Xie S, van Rossum R, Bermejo I, Geleijnse G, Aben K, van Erning F, Lemmens V, Dekker A, Verbeek X. Identifying Confounders Using Bayesian Networks and Estimating Treatment Effect in Prostate Cancer With Observational Data. JCO Clin Cancer Inform 2023; 7:e2200080. [PMID: 36595730 DOI: 10.1200/cci.22.00080] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
PURPOSE Randomized controlled trials are considered the golden standard for estimating treatment effect but are costly to perform and not always possible. Observational data, although readily available, is sensitive to biases such as confounding by indication. Structure learning algorithms for Bayesian Networks (BNs) can be used to discover the underlying model from data. This enables identification of confounders through graph analysis, although the model might contain noncausal edges. We propose using a blacklist to aid structure learning in finding causal relationships. This is illustrated by an analysis into the effect of active treatment (v observation) in localized prostate cancer. METHODS In total, 4,121 prostate cancer records were obtained from the Netherlands Cancer Registry. Subsequently, we developed a (causal) BN using structure learning while precluding noncausal relations. Additionally, we created several Cox proportional hazards models, each correcting for a different set of potential confounders (including propensity scores). Model predictions for overall survival were compared with expected survival on the basis of the general population using data from Statistics Netherlands (Centraal Bureau voor de Statistiek). RESULTS Structure learning precluding noncausal relations resulted in a causal graph but did not identify significant edges toward treatment; they were added manually. Graph analysis identified year of diagnosis and age as confounders. The BN predicted a treatment effect of 1 percentage point at 10 years. Chi-squared analysis found significant associations between year of diagnosis, age, stage, and treatment. Propensity score correction was successful. Adjusted Cox models predicted significant treatment effect around 3 percentage points at 10 years. CONCLUSION A blacklist in conjunction with structure learning can result in a causal BN that can be used for confounder identification. Treatment effect found here is close to the 5 percentage point found in the literature.
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Affiliation(s)
- Melle Sieswerda
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands.,Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Shixuan Xie
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Ruby van Rossum
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Inigo Bermejo
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Gijs Geleijnse
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Katja Aben
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Felice van Erning
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
| | - Valery Lemmens
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - André Dekker
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Reproduction, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Xander Verbeek
- Department of Research and Development, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
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Ahlberg MS, Garmo H, Adami HO, Andrén O, Johansson JE, Steineck G, Holmberg L, Bill-Axelson A. Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study. BMJ Open 2022; 12:e057242. [PMID: 36581423 PMCID: PMC9806038 DOI: 10.1136/bmjopen-2021-057242] [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] [Indexed: 12/30/2022] Open
Abstract
OBJECTIVE Although surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk of prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence five and 10 years after radical prostatectomy. DESIGN Prospective cohort study. Stratification by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3) and negative or positive surgical margins. SETTING Between 1989 and 1998, 14 urological centres in Scandinavia randomised patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. PARTICIPATION All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible. Four patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). PRIMARY OUTCOME MEASURES Cumulative incidences and absolute differences in metastatic disease and prostate cancer death. RESULTS We analysed 302 patients with complete follow-up during a median of 24 years. Median preoperative PSA was 9.8 ng/mL and median age was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12%, respectively. The long-term probabilities were higher for pT ≥3 versus pT2 and for positive versus negative surgical margins. Limitations include small size of the cohort. CONCLUSION Many patients with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy could stop follow-up earlier than 10 years after radical prostatectomy.
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Affiliation(s)
| | - Hans Garmo
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Hans-Olov Adami
- Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Ove Andrén
- Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Jan-Erik Johansson
- Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Gunnar Steineck
- Department of Oncology, Sahlgrenska Academy at the University of Gothenburg, Division of Clinical Cancer Epidemiology, Institute of Clinical Sciences, Gothenburg, Sweden
| | - Lars Holmberg
- School of Cancer & Pharmaceutical Sciences, King's College London, London, UK
| | - Anna Bill-Axelson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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KARKİN K, VURUŞKAN E. Two-year profile of the records of patients referred to Adana city hospital urology clinic due to PSA high in primary care: a retrospective review. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1050771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objective: To retrospectively evaluate the two-year records of patients referred to Adana City Training and Research Hospital by family physicians because of high prostate specific antigen (PSA), and to reveal the profile and related outcomes for clinical practices of family physicians about prostate cancer screening.
Material and Method: The files of 102 patients, who were referred to our clinic by their family physicians due to high PSA between April 2019 and May 2021, were retrospectively evaluated. Demographic data of patients, presence of additional disease, family history, control serum PSA value examined in family medicine centers and in our hospital at time of first admission, complete urinalysis (TIT), ultrasonography (USG) and multiparametric magnetic resonance (mpMR) findings, transrectal ultrasonographic biopsy (TRUS-BX) results and biopsy were noted. The treatments administered according to the results (radical prostatectomy, radiotherapy, hormone therapy, chemotherapy) were recorded.
Results: The mean age of the patients was 52.8±8.9 years. The PSA value of the patients at time of admission was 8.0±3.8 ng/ml. The mean PSA values measured at the time of admission to primary care and at the time of admission to Adana clinic after referral were 8.0±3.8 ng/ml and 8.0±3.0 ng/ml, respectively. There was no statistically significant difference between these values (p=0.2). Among all the patients presenting with elevated PSA, 36 (35%) patients underwent TRUS Bx, had prostate cancer as a result of pathology and underwent radical prostatectomy, which was the most common definitive treatment method with statistical significance (p
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Affiliation(s)
- Kadir KARKİN
- Sağlık bilimleri üniversitesi Adana şehir eğitim araştırma hastanesi
| | - Ediz VURUŞKAN
- Sağlık bilimleri üniversitesi Adana şehir eğitim araştırma hastanesi
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Fischer-Valuck BW, Baumann BC, Brown SA, Filson CP, Weiss A, Mueller R, Liu Y, Brenneman RJ, Sanda M, Michalski JM, Gay HA, James Rao Y, Pattaras JG, Jani AB, Hershatter B, Patel SA. Treatment Patterns and Overall Survival Outcomes Among Patients Aged 80 yr or Older with High-risk Prostate Cancer. EUR UROL SUPPL 2022; 37:80-89. [PMID: 35243392 PMCID: PMC8883189 DOI: 10.1016/j.euros.2021.12.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2021] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Elderly patients diagnosed with high-risk prostate cancer (PCa) present a therapeutic dilemma of balancing treatment of a potentially lethal malignancy with overtreatment of a cancer that may not threaten life expectancy. OBJECTIVE To investigate treatment patterns and overall survival outcomes in this group of patients. DESIGN SETTING AND PARTICIPANTS A retrospective cohort study was conducted. We queried the National Cancer Database for high-risk PCa in patients aged 80 yr or older diagnosed during 2004-2016. INTERVENTION Eligible patients underwent no treatment following biopsy (ie, observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Kaplan-Meier, log rank, and multivariate Cox proportional hazard regression was performed to compare overall survival (OS). RESULTS AND LIMITATIONS A total of 19 920 men were eligible for analysis, and the most common treatment approach was RT + ADT (7401 patients; 37.2%). Observation and ADT alone declined over time (59.3% in 2004 vs 47.5% in 2016). There was no observed difference in OS between observation and ADT alone (adjusted hazard ratio [HR] 1.04, 95% confidence interval [CI], 0.99-1.09; p = 0.105). Definitive local treatment was associated with improved OS compared with ADT alone (RT alone, HR 0.54, 95% CI, 0.50-0.59, p < 0.0001; ADT + RT, HR 0.48, 95% CI, 0.46-0.50, p < 0.0001; surgery, HR 0.50, 95% CI, 0.42-0.59, p < 0.0001). CONCLUSIONS This analysis demonstrates that the use of definitive local therapy, including surgery or RT ± ADT, is increasing and is associated with a 50% reduction in overall mortality compared with observation or ADT alone. While prospective validation is warranted, elderly men with high-risk disease eligible for definitive management should be counseled on the risks, including a possible compromise in OS, with deferring definitive management. PATIENT SUMMARY Elderly men are more often diagnosed with higher-risk prostate cancer but are less likely to receive curative treatment options than younger men. Our analysis demonstrates that for men ≥80 yr of age with high-risk prostate cancer, definitive local therapy, including surgery or radiation therapy and/or androgen deprivation therapy, is associated with a 50% reduction in overall mortality compared with observation or androgen deprivation therapy alone. We therefore recommend that life expectancy (ie, physiologic age) be taken into account, over chronologic age, and that elderly men with good life expectancy (eg, >5 yr; minimal comorbidity) should be offered definitive, life-prolonging therapy.
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Affiliation(s)
- Benjamin W Fischer-Valuck
- Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
- Department of Radiation Oncology, Springfield Clinic, Springfield, IL, USA
| | - Brian C Baumann
- Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, USA
| | - Simon A Brown
- Department of Radiation Oncology, Springfield Clinic, Springfield, IL, USA
| | - Christopher P Filson
- Department of Urology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Aaron Weiss
- Department of Urology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Ryan Mueller
- Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, USA
| | - Yuan Liu
- Department of Biostatistics & Bioinformatics, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Randall J Brenneman
- Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, USA
| | - Martin Sanda
- Department of Urology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Jeff M Michalski
- Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, USA
| | - Hiram A Gay
- Department of Radiation Oncology, Washington University in St. Louis, St. Louis, MO, USA
| | - Yuan James Rao
- Department of Radiation Oncology, George Washington University, Washington, DC, USA
| | - John G Pattaras
- Department of Urology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Ashesh B Jani
- Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Bruce Hershatter
- Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
| | - Sagar A Patel
- Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
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Rasouli MA, Moradi G, Zareie B, Sofimajidpour H, Tozandehjani S, Zafari H, Gholami F, Shahsavari S, Hassani P, Mohammadian M. Overall survival and prognostic factors prostate cancer in Kurdistan Province-Iran: a population-based study (2011-2018). BMC Cancer 2021; 21:1314. [PMID: 34876069 PMCID: PMC8653556 DOI: 10.1186/s12885-021-09078-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 11/29/2021] [Indexed: 12/09/2022] Open
Abstract
Background The population-based survival rate is affected by the quality and effectiveness of health care systems. Overall, the survival of prostate cancer (PC) patients has improved over the past two decades worldwide. This study aimed to determine the overall survival rate and correlate it with the prognostic factors in patients with PC diagnosed in Kurdistan province. Methods In a retrospective cohort study, 410 PC patients registered in Kurdistan province population-based cancer registry from March 2011 to 2018 were recruited. Kaplan–Meier method and log-rank test were used to analyze the overall survival rates of PC patients. A Multivariate Cox regression model was used to determine adjusted hazard ratios for different variables. Results Of 410 patients with PC, 263 (64.1%) died within seven years due to the disease. The 1, 3, and 5 years survival rates were 93, 64.1, and 40.7%, respectively. According to the results of multiple Cox regression, the following factors were significantly related to PC survival: age at diagnosis (≥81-years old) (HR=2.23, 95% CI: 1.23-4.42) and 71-80 years old was (HR=1.26, 95% CI: 1.12-2.31), occupation (employee) (HR=0.42, 95% CI: 0.20–0.87), educational level: academic (HR=0.78, 95% CI: 0.64–0.91), AJCC stage of disease (HR=2.18, 95% CI: 1.9–3.68), Gleason score ≥ 9 (HR=7.12, 95% CI: 5.35–10.28), and Gleason score= 8 (HR=4.16, 95% CI: 2.50–6.93). There was less mortality rate among the patients who had received active care, radical prostatectomy, radiotherapy, combined treatment, and orchiectomy had a lower mortality rate than those who received no treatment (P<0.05). Conclusions This study demonstrated that factors such as age at diagnosis, level of education, occupation, AJCC stage of disease, Gleason score, and type of treatments were influential factors in the survival of PC patients in Kurdistan province and needed more attention.
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Affiliation(s)
- Mohammad Aziz Rasouli
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Ghobad Moradi
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.,Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Bushra Zareie
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Heshmatollah Sofimajidpour
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran. .,Department of Urology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
| | - Sima Tozandehjani
- Department of Biological Sciences, Faculty of Science, University of Kurdistan, Sanandaj, Iran
| | - Hedyeh Zafari
- Department of Biological Sciences, Faculty of Science, University of Kurdistan, Sanandaj, Iran
| | - Fatemeh Gholami
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Sonia Shahsavari
- Social Determinants of Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Parisa Hassani
- Department of Biological Sciences, Faculty of Science, University of Kurdistan, Sanandaj, Iran
| | - Mahshid Mohammadian
- Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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21
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Lantz A, Bock D, Akre O, Angenete E, Bjartell A, Carlsson S, Modig KK, Nyberg M, Kollberg KS, Steineck G, Stranne J, Wiklund P, Haglind E. Functional and Oncological Outcomes After Open Versus Robot-assisted Laparoscopic Radical Prostatectomy for Localised Prostate Cancer: 8-Year Follow-up. Eur Urol 2021; 80:650-660. [PMID: 34538508 DOI: 10.1016/j.eururo.2021.07.025] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 07/28/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Radical prostatectomy reduces mortality among patients with localised prostate cancer. Evidence on whether different surgical techniques can affect mortality rates is lacking. OBJECTIVE To evaluate functional and oncological outcomes 8 yr after robot-assisted laparoscopic prostatectomy (RALP) and open retropubic radical prostatectomy (RRP). DESIGN, SETTING, AND PARTICIPANTS We enrolled 4003 patients in a prospective, controlled, nonrandomised trial comparing RALP and RRP in 14 Swedish centres between 2008 and 2011. Data for functional outcomes were assessed via validated patient questionnaires administered preoperatively and at 12 and 24 mo and 8 yr after surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary endpoint was urinary incontinence. Functional outcomes at 8 yr were analysed using the modified Poisson regression approach. RESULTS AND LIMITATIONS Urinary incontinence was not significantly different at 8 yr after surgery between RALP and RRP (27% vs 29%; adjusted risk ratio [aRR] 1.05, 95% confidence interval [CI] 0.90-1.23). Erectile dysfunction was significantly lower in the RALP group (66% vs 70%; aRR 0.93, 95% CI 0.87-0.99). Prostate cancer-specific mortality (PCSM) was significantly lower in the RALP group at 8 yr after surgery (40/2699 vs 25/885; aRR 0.56, 95% CI 0.34-0.93). Differences in oncological outcomes were mainly seen in the group with high D'Amico risk, with a lower risk of positive surgical margins (21% vs 34%), biochemical recurrence (51% vs 69%), and PCSM (14/220 vs 11/77) for RALP versus RRP. The main limitation is the nonrandomised design. CONCLUSIONS In this prospective multicentre controlled trial, PCSM at 8 yr after surgery was lower for RALP in comparison to RRP. A causal relationship between surgical technique and mortality cannot be inferred, but the result confirms that RALP is oncologically safe. Taken together with better short-term results reported elsewhere, our findings confirm that implementation of RALP may continue. PATIENT SUMMARY Our study comparing two surgical techniques for removal of the prostate for localised prostate cancer shows that a robot-assisted minimally invasive technique is safe in the long term. Together with previous results showing some better short-term effects with this approach, our findings support continued use of robot-assisted surgery.
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Affiliation(s)
- Anna Lantz
- Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
| | - David Bock
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Olof Akre
- Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
| | - Eva Angenete
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital-Västra Götaland/Östra, Gothenburg, Sweden
| | - Anders Bjartell
- Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Division of Urological Cancers, Lund University, Lund, Sweden
| | - Stefan Carlsson
- Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
| | - Katarina Koss Modig
- Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Sahlgrenska University Hospital-Västra Götaland, Gothenburg, Sweden
| | - Martin Nyberg
- Department of Urology, Skåne University Hospital, Malmö, Sweden; Department of Translational Medicine, Division of Urological Cancers, Lund University, Lund, Sweden
| | - Karin Stinesen Kollberg
- Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Social Work, Institute of Social Sciences, University of Gothenburg, Gothenburg, Sweden
| | - Gunnar Steineck
- Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Johan Stranne
- Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Urology, Sahlgrenska University Hospital-Västra Götaland, Gothenburg, Sweden
| | - Peter Wiklund
- Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Urology, Icahn School of Medicine, Mount Sinai Health System, New York, NY, USA
| | - Eva Haglind
- Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital-Västra Götaland/Östra, Gothenburg, Sweden
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22
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Ullevig SL, Bacich DJ, Gutierrez JM, Balarin A, Lobitz CA, O'Keefe DS, Liss MA. Feasibility of dietary folic acid reduction intervention for men on active surveillance for prostate cancer. Clin Nutr ESPEN 2021; 44:270-275. [PMID: 34330478 DOI: 10.1016/j.clnesp.2021.06.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 05/05/2021] [Accepted: 06/03/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS Fortification of the US food supply has increased folic acid intake and resulted in a concomitant decrease in neural tube defects in women. However, a body evidence supports the hypothesis that increased circulating folate levels due to excessive dietary or supplemental folic acid may be harmful for men with prostate cancer. Therefore, this pilot study aimed to investigate the feasibility of a reduced folic acid dietary intervention in men on an active surveillance monitoring program for prostate cancer. METHODS Men with low-grade prostate cancer enrolled into a 12-week dietary folic acid reduction diet. Primary outcome was red blood cell (RBC) folate reduction at 12 weeks. Other outcomes include serum folate, homocysteine, and vitamin B12 levels. The number of patients who complete the trial and reasons for disenrollment or dropout were also assessed. RESULTS Twenty-eight participants were enrolled into the dietary intervention study. Six participants withdrew from the study and a total of 21 participants completed all baseline and week 12 biochemical assessments. Only 18 participants completed all dietary questionnaires. Participants withdrew from the study due to difficulty with the diet or personal reasons. A substantial reduction was noted in serum folate (p < 0.007), RBC folate (p < 0.001) and dietary consumption of folic acid from foods (p = 0.003) and supplements (p = 0.003) without reduction in serum homocysteine or vitamin B12. Although an overall decrease in PSA from baseline to twelve weeks was found, the reduction was not significant (-3.55 ng/mL, p = 0.197). CONCLUSIONS This phase 1 feasibility study reduced dietary folic acid intake from food and supplements and successfully lowered serum and RBC folate without resulting harmful effects. Data from this study supports future intervention trials with a larger prostate cancer active surveillance population and has the potential to reduce prostate cancer progression. There are no interventions to reduce progression of prostate cancer in man on active surveillance.
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Affiliation(s)
- Sarah L Ullevig
- College for Health, Community and Policy, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, United States
| | - Dean J Bacich
- Department of Urology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78249, United States
| | - Jose M Gutierrez
- Department of Urology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78249, United States
| | - Ashton Balarin
- College for Health, Community and Policy, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, United States
| | - C Austin Lobitz
- College for Health, Community and Policy, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, United States
| | - Denise S O'Keefe
- Department of Urology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78249, United States
| | - Michael A Liss
- Department of Urology, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78249, United States; College of Pharmacy, University of Texas at Austin, 110 Inner Campus Drive, Austin, TX 78705, United States.
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23
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Wagner H, Kenk M, Fraser M, Berlin A, Fleshner N. Biorepositories and Databanks for the Development of Novel Biomarkers for Genitourinary Cancer Prevention and Management. Eur Urol Focus 2021; 7:513-521. [PMID: 34167926 DOI: 10.1016/j.euf.2021.06.002] [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: 04/09/2021] [Revised: 05/15/2021] [Accepted: 06/04/2021] [Indexed: 11/27/2022]
Abstract
CONTEXT Translational research in uro-oncology depends on the availability of high-quality biospecimens and associated data to advance precision medicine and improve clinical outcomes. Procurement, storage, and annotation of these specimens represent critical steps towards this end. OBJECTIVE To review best-practice experiences gained via the McCain GU BioBank, a repository of more than 750 000 biospecimens obtained from more than 16 000 patients attending clinics at the University Health Network in Toronto, Canada. EVIDENCE ACQUISITION The review summarizes our experiences at a large single-institution genitourinary oncology biorepository. EVIDENCE SYNTHESIS Key findings are placed in the context of emerging trends in genitourinary oncology, with a focus on integration of molecular profiling and clinical data with traditional biorepository management. Proposed approaches provide high-quality biospecimens with comprehensive and reliable clinical data that can fuel innovation and discovery in research. CONCLUSIONS Biorepositories are vital for improving clinical outcomes and advancing personalized medicine. High-quality biospecimens and their associated clinical data are crucial for validation of biomarkers in oncology. Efforts to procure, store, and annotate clinical specimens represent critical steps in translational research. Elements such as biobank size, biospecimen types, disease cohorts, predetermined collection protocols, broad informed consent, sample handling and storage protocols, and available infrastructure directly influence the effectiveness and capacity of a biobank. PATIENT SUMMARY Biorepositories, or biobanks, are facilities that store biospecimens such as blood, urine, or tissue (usually collected from humans) for use in research. Biobanks have become an important resource in medical research, as they provide high-quality specimens to support different types of contemporary research such as genomics, biomarker discovery, and personalized medicine. Clinical management and treatment of genitourinary cancers, such as prostate, kidney, and bladder cancers, are particularly suited for biomarker research. The provision of biospecimens and their associated clinical data have become crucial for validation of biomarkers in these cancers.
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Affiliation(s)
- Heidi Wagner
- McCain GU BioBank, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
| | - Miran Kenk
- McCain GU BioBank, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
| | - Michael Fraser
- McCain GU BioBank, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Faculty of Medicine, University of Toronto, Toronto, Canada; Canadian Prostate Cancer Genome Network, Toronto, Canada
| | - Alejandro Berlin
- Faculty of Medicine, University of Toronto, Toronto, Canada; Canadian Prostate Cancer Genome Network, Toronto, Canada; Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
| | - Neil Fleshner
- McCain GU BioBank, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Faculty of Medicine, University of Toronto, Toronto, Canada
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24
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Nakayama A, Ide H, Lu Y, Takei A, Fukuda K, Osaka A, Arai G, Horie S, Okada H, Saito K. Effects of Curcumin Combined With the 5-alpha Reductase Inhibitor Dutasteride on LNCaP Prostate Cancer Cells. In Vivo 2021; 35:1443-1450. [PMID: 33910821 DOI: 10.21873/invivo.12396] [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: 01/05/2021] [Revised: 02/07/2021] [Accepted: 02/08/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND/AIM Curcumin is a natural compound of turmeric, which inhibits prostate cancer cell proliferation. This study examined whether treatment of LNCaP prostate cancer cells with the combination of curcumin and dutasteride, a 5-alpha reductase inhibitor, affect proliferation and the amount of testosterone and dihydrotestosterone. MATERIALS AND METHODS LNCaP Cells were incubated with curcumin or the combination of curcumin and dutasteride and cell proliferation was measured at 72 h. LC-MS/MS was used to determine testosterone and dihydrotestosterone concentrations in prostate cancer cells. RESULTS Curcumin combined with dutasteride suppressed proliferation and affected apoptosis of LNCaP cells. The combination of curcumin and dutasteride also reduced the amount of testosterone and dihydrotestosterone in LNCaP cells. The secretion of prostate-specific antigen was inhibited by the combination treatment in a dose-dependent manner. CONCLUSION Treatment with the combination of curcumin and dutasteride may interfere with the intra-tumoral androgen activity.
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Affiliation(s)
- Akinori Nakayama
- Department of Urology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Hisamitsu Ide
- Department of Urology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan;
| | - Yan Lu
- Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo, Japan
| | - Ayano Takei
- Collaborative Research Center, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Kazunori Fukuda
- Collaborative Research Center, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Akiyoshi Osaka
- Department of Urology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Gaku Arai
- Department of Urology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Shigeo Horie
- Department of Urology, Juntendo University, Graduate School of Medicine, Tokyo, Japan
| | - Hiroshi Okada
- Department of Urology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
| | - Kazutaka Saito
- Department of Urology, Dokkyo Medical University Saitama Medical Center, Saitama, Japan
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Nocera L, Wenzel M, Collà Ruvolo C, Würnschimmel C, Tian Z, Gandaglia G, Fossati N, Chun FKH, Mirone V, Graefen M, Shariat SF, Saad F, Montorsi F, Briganti A, Karakiewicz PI. The effect of race/ethnicity on active treatment rates among septuagenarian or older low risk prostate cancer patients. Urol Oncol 2021; 39:785.e11-785.e17. [PMID: 33992522 DOI: 10.1016/j.urolonc.2021.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 03/04/2021] [Accepted: 04/04/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Race/ethnicity may predispose to higher active treatment rates in septuagenarian or older low risk prostate cancer (CaP) patients. We tested this hypothesis within a contemporary North American cohort. MATERIAL AND METHODS We relied on the Surveillance, Epidemiology and End Results (SEER) database 2010-2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting definitive treatment administration. Treatment rates (no local treatment [NLT], external beam radiotherapy [EBRT], radical prostatectomy [RP] and brachytherapy) were examined without, as well as with adjustment for age, socioeconomic status, marital status, residence type, year of diagnosis, other-cause mortality, prostate-specific antigen (PSA) and clinical T stage across races/ethnicities. Moreover, temporal trend analyses were performed. RESULTS Of 15,118 septuagenarian or older low risk CaP patients, 11,509 (76.1%) were Caucasian, 1,613 (10.7%) African-American, 1,293 (8.5%) Hispanic/Latino and 703 (4.7%) Asian. No clinically meaningful differences were recorded between races/ethnicities with respect to age at diagnosis, PSA, clinical T stage and percentage of positive biopsy cores. Conversely, clinically meaningful and statistically significant differences were identified in socioeconomic status and treatment modality. Specifically, treatment rates ranged as follows: NLT 41.8-48.2, EBRT 23.0-29.9, RP 13.8-21.8 and brachytherapy 6.4-9.9% across race/ethnicies. After adjustment for patient and tumor characteristics, NLT, EBRT, RP and brachytherapy rates showed virtually no residual heterogeneity between races/ethnicities. Finally, in temporal trend analyses, EBRT rates decreased in all races/ethnicities. Conversely, RP and brachytherapy rates did not change over time. CONCLUSION The rates of active treatment in septuagenarian or older low risk CaP patients are surprisingly elevated in all races/ethnicities, even though they decreased over time. All differences in active treatment rates according to race/ethnicity depend on baseline patient and tumor characteristics.
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Affiliation(s)
- Luigi Nocera
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Mike Wenzel
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Claudia Collà Ruvolo
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Department of Urology, University of Naples Federico II, Naples, Italy
| | - Christoph Würnschimmel
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Zhe Tian
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada
| | - Giorgio Gandaglia
- Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Nicola Fossati
- Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Felix K H Chun
- Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Vincenzo Mirone
- Department of Urology, University of Naples Federico II, Naples, Italy
| | - Markus Graefen
- Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Shahrokh F Shariat
- Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Departments of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, University of Texas Southwestern, Dallas, TX; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan
| | - Fred Saad
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada
| | - Francesco Montorsi
- Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Alberto Briganti
- Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Pierre I Karakiewicz
- Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada
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Yang CH, Lin YS, Ou YC, Weng WC, Huang LH, Lu CH, Hsu CY, Tung MC. Biochemical recurrence of pathological T2+ localized prostate cancer after robotic-assisted radical prostatectomy: A 10-year surveillance. World J Clin Cases 2021; 9:1026-1036. [PMID: 33644166 PMCID: PMC7896665 DOI: 10.12998/wjcc.v9.i5.1026] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 12/13/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND pT2+ prostate cancer (PCa), a term first used in 2004, refers to organ-confined PCa characterized by a positive surgical margin (PSM) without extracapsular extension. Patients with a PSM are vulnerable to biochemical recurrence (BCR) following radical prostatectomy (RP); however, whether adjuvant radiotherapy (aRT) is imperative to PSM after RP remains controversial. This study had the longest follow-up on pT2+ PCa after robotic-assisted RP since 2004. Moreover, we discussed our viewpoints on pT2+ PCa based on real-world experiences.
AIM To conclude a 10-year surveillance on pT2+ PCa and compare our results with those of the published literature.
METHODS Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled. Two serial tests of prostate specific antigen (PSA) ≥ 0.2 ng/mL were defined as BCR. Various designed factors were analyzed using statistical tools for BCR risk. SAS 9.4 was applied and significance was defined as P < 0.05. Univariate, multivariate, linear regression, and receiver operating characteristic (ROC) curve analyses were performed for statistical analyses.
RESULTS With a median follow-up period of 9 years, 25 (52%) patients had BCR (BCR group), and the remaining 23 (48%) patients did not (non-BCR group). The median time for BCR test was 4 years from the first postoperative PSA nadir. Preoperative PSA was significantly different between the BCR and non-BCR groups (P < 0.001), and ROC curve analysis of preoperative PSA suggested a cut-off value of 19.09 ng/mL (sensitivity, 0.600; specificity: 0.739). The linear regression analysis showed no correlation between time to BCR and preoperative PSA (Pearson’s correlation, 0.13; adjusted R2 = 0.026).
CONCLUSION Robotic-assisted RP in pT2+ PCa of worse conditions can provide better BCR-free survival. A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+ PCa BCR rate. Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR. Based on our experiences and review of the literature, we do not recommend routine aRT for pT2+ PCa.
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Affiliation(s)
- Che Hseuh Yang
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
| | - Yi Sheng Lin
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
| | - Yen Chuan Ou
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
| | - Wei Chun Weng
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
| | - Li Hua Huang
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
| | - Chin Heng Lu
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
| | - Chao Yu Hsu
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
| | - Min Che Tung
- Division of Urology, Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 435403, Taiwan
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Naccarato AMEP, Consuelo Souto S, Matheus WE, Ferreira U, Denardi F. Quality of life and sexual health in men with prostate cancer undergoing radical prostatectomy. Aging Male 2020; 23:346-353. [PMID: 30040004 DOI: 10.1080/13685538.2018.1486397] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
Abstract
The aim of this study was to evaluate the relationship between quality of life, erectile function and group psychotherapy in patients with prostate cancer undergoing radical prostatectomy. Sixty patients were evaluated for erectile function (IIEF-5), quality of life (SF-36SF), urinary incontinence (ICQI-SF and ICQI-OAB). Thirty of them had group psychotherapy two weeks before and 12 weeks after surgery. Patients who underwent group psychotherapy had better scores in IIEF-5, satisfaction with life in general, satisfaction with sexual life and in partner relationship; better results of SF-36SF, excepting two domains: bodily pain and role emotional. There were significant correlations between IIEF-5 and perception of discomfort (p = .030), physical functioning (p = .021), physical component (p = .005) and role emotional (p = .009) in patients undergoing group psychotherapy. In patients who didn't have group psychotherapy there were significant correlations between ICQI-OAB and perception of discomfort (p = .025), social functioning (p = .052) and role emotional (p = .034); between ICQI-SF and perception of discomfort (p = .0001). Group psychotherapy has a positive impact in quality of life and erectile function. There was no difference in the urinary function of the two groups. Further studies are necessary to identify the impact of self-perception and self-knowledge in the postoperative management of radical prostatectomy.
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Affiliation(s)
- Angela M E P Naccarato
- Department of Urologic Oncology, State University of Campinas - Unicamp, Campinas, Brazil
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Talebpour M, Khatami F, Aghaii M, Aghamir SMK. New technique of inguinal hernia repair during prostatectomy. JOURNAL OF CLINICAL UROLOGY 2020. [DOI: 10.1177/2051415820961301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Background: Several benefits of inguinal hernia repair concurrent with simple prostatectomy have been proposed recently. For the first time we represent this surgery in the form of retroperitoneal mesh insertion without an additional surgical cut for the inguinal hernia repair. Methods: We selected 19 patients for this trial of a new surgery method. The simple prostatectomy was performed and from the same surgical cut the hernia sac recognized. Two methods of prostatectomy surgery were undertaken: Millin’s and Freyer’s prostatectomy. The retroperitoneal insertion of monofilament polypropylene was undertaken for hernia repair. Results: All patients were prospectively followed for three years for clinical outcomes and hernia recurrence. No complications after surgery, including wound infection, pelvic collections, sepsis and recurrence of the hernia were seen. Conclusions: Our new retroperitoneal mesh insertion technique is safe, effective and simultaneously practical with simple prostatectomy. This new method is strongly recommended to other surgeons, since it has beneficial results with no noteworthy raise in operative duration or further complications.
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Affiliation(s)
- Mohammad Talebpour
- Department of General Surgery, Tehran University of Medical Sciences, Iran
| | - Fatemeh Khatami
- Urology Research Center, Tehran University of Medical Sciences, Iran
| | - Maryam Aghaii
- Urology Research Center, Tehran University of Medical Sciences, Iran
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Results of a randomized trial of treatment modalities in patients with low or early-intermediate risk prostate cancer (PREFERE trial). J Cancer Res Clin Oncol 2020; 147:235-242. [PMID: 32886212 PMCID: PMC7810635 DOI: 10.1007/s00432-020-03327-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/17/2020] [Indexed: 12/11/2022]
Abstract
Purpose The optimal treatment for patients with low to early-intermediate risk prostate cancer (PCa) remains to be defined. The randomized PREFERE trial (DRKS00004405) aimed to assess noninferiority of active surveillance (AS), external-beam radiotherapy (EBRT), or brachytherapy by permanent seed implantation (PSI) vs. radical prostatectomy (RP) for these patients. Methods PREFERE was planned to enroll 7600 patients. The primary endpoint was disease specific survival. Patients with PCa stage ≤ cT2a, cN0/X, M0, PSA ≤ 10 ng/ml and Gleason-Score ≤ 3 + 4 at reference pathology were eligible. Patients were allowed to exclude one or two of the four modalities, which yielded eleven combinations for randomization. Sixty-nine German study centers were engaged in PREFERE. Results Of 2251 patients prescreened between 2012 and 2016, 459 agreed to participate in PREFERE. Due to this poor accrual, the trial was stopped. In 345 patients reference pathology confirmed inclusion criteria. Sixty-nine men were assigned to RP, 53 to EBRT, 93 to PSI, and 130 to AS. Forty patients changed treatment shortly after randomization, 21 to AS. Forty-eight AS patients with follow-up received radical treatment. Median follow-up was 19 months. Five patients died, none due to PCa; 8 had biochemical progression after radical therapy. Treatment-related acute grade 3 toxicity was reported in 3 RP patients and 2 PSI patients. Conclusions In this prematurely closed trial, we observed an unexpected high rate of termination of AS and an increased toxicity related to PSI. Patients hesitated to be randomized in a multi-arm trial. The optimal treatment of low and early-intermediate risk PCa remains unclear. Electronic supplementary material The online version of this article (10.1007/s00432-020-03327-2) contains supplementary material, which is available to authorized users.
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Saito R, Tanaka N, Aizawa T, Imoto H, Yamamura A, Aoki T, Kawamorita N, Musha H, Ohnuma S, Motoi F, Ito A, Kamei T, Naitoh T, Unno M. Tips for operation of inguinal hernia after implantation of artificial urinary sphincter following radical prostatectomy: report of two cases. J Surg Case Rep 2020; 2020:rjaa150. [PMID: 32855787 PMCID: PMC7444616 DOI: 10.1093/jscr/rjaa150] [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: 04/13/2020] [Accepted: 05/03/2020] [Indexed: 11/12/2022] Open
Abstract
Urinary incontinence is one of the common complications after radical prostatectomy along with inguinal hernia. Artificial urethral sphincter implantation is widely accepted as a treatment option. We report two surgical cases of inguinal hernia after artificial urethral sphincter implantation for urinary incontinence following radical prostatectomy. In Case 1, since the device went through the inguinal canal, adhesion around the pubis was extremely hard. In Case 2, the device was placed on the ventral side of the rectus abdominis muscle, so it was operable almost as normal. In each case, the surgical procedure was considered carefully after confirming the location of the device by preoperative computed tomography and ultrasonography. Hernia repair was successfully performed using the Lichtenstein method. There are few reports regarding surgical repair of inguinal hernia following artificial urinary sphincter implantation. Preoperative image and appropriate choice of approach could facilitate safe and secure surgery.
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Affiliation(s)
- Ryusuke Saito
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Naoki Tanaka
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Takashi Aizawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hirofumi Imoto
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Akihiro Yamamura
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Takeshi Aoki
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Naoki Kawamorita
- Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hiroaki Musha
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Shinobu Ohnuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Fuyuhiko Motoi
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Akihiro Ito
- Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Takashi Kamei
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Takeshi Naitoh
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Wade J, Noble S, Garfield K, Young G, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Blazeby J, Bryant R, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Gnanapragasam V, Hughes O, Kockelbergh R, Kynaston H, Paul A, Paez E, Powell P, Prescott S, Rosario D, Rowe E, Neal D. Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT. Health Technol Assess 2020; 24:1-176. [PMID: 32773013 PMCID: PMC7443739 DOI: 10.3310/hta24370] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. OBJECTIVES To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years. DESIGN A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. SETTING Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. PARTICIPANTS Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. INTERVENTIONS The interventions were active monitoring, radical prostatectomy and radical radiotherapy. TRIAL PRIMARY OUTCOME MEASURE Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. SECONDARY OUTCOME MEASURES Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. RESULTS There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy). LIMITATIONS A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. CONCLUSIONS At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. TRIAL REGISTRATION Current Controlled Trials ISRCTN20141297. FUNDING This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.
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Affiliation(s)
- Freddie C Hamdy
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | | | - J Athene Lane
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Malcolm Mason
- School of Medicine, University of Cardiff, Cardiff, UK
| | - Chris Metcalfe
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Peter Holding
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Julia Wade
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Sian Noble
- Bristol Medical School, University of Bristol, Bristol, UK
| | | | - Grace Young
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Michael Davis
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Tim J Peters
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Emma L Turner
- Bristol Medical School, University of Bristol, Bristol, UK
| | | | - Jon Oxley
- Department of Cellular Pathology, North Bristol NHS Trust, Bristol, UK
| | - Mary Robinson
- Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
| | - John Staffurth
- Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK
| | - Eleanor Walsh
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Jane Blazeby
- Bristol Medical School, University of Bristol, Bristol, UK
| | - Richard Bryant
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Prasad Bollina
- Department of Urology and Surgery, Western General Hospital, University of Edinburgh, Edinburgh, UK
| | - James Catto
- Academic Urology Unit, University of Sheffield, Sheffield, UK
| | - Andrew Doble
- Department of Urology, Addenbrooke's Hospital, Cambridge, UK
| | - Alan Doherty
- Department of Urology, Queen Elizabeth Hospital, Birmingham, UK
| | - David Gillatt
- Department of Urology, Southmead Hospital and Bristol Urological Institute, Bristol, UK
| | | | - Owen Hughes
- Department of Urology, Cardiff and Vale University Health Board, Cardiff, UK
| | - Roger Kockelbergh
- Department of Urology, University Hospitals of Leicester, Leicester, UK
| | - Howard Kynaston
- Department of Urology, Cardiff and Vale University Health Board, Cardiff, UK
| | - Alan Paul
- Department of Urology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Edgar Paez
- Department of Urology, Freeman Hospital, Newcastle upon Tyne, UK
| | - Philip Powell
- Department of Urology, Freeman Hospital, Newcastle upon Tyne, UK
| | - Stephen Prescott
- Department of Urology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Derek Rosario
- Academic Urology Unit, University of Sheffield, Sheffield, UK
| | - Edward Rowe
- Department of Urology, Southmead Hospital and Bristol Urological Institute, Bristol, UK
| | - David Neal
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
- Academic Urology Group, University of Cambridge, Cambridge, UK
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Rethinking prostate cancer screening: could MRI be an alternative screening test? Nat Rev Urol 2020; 17:526-539. [PMID: 32694594 DOI: 10.1038/s41585-020-0356-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2020] [Indexed: 12/14/2022]
Abstract
In the past decade rigorous debate has taken place about population-based screening for prostate cancer. Although screening by serum PSA levels can reduce prostate cancer-specific mortality, it is unclear whether the benefits outweigh the risks of false-positive results and overdiagnosis of insignificant prostate cancer, and it is not recommended for population-based screening. MRI screening for prostate cancer has the potential to be analogous to mammography for breast cancer or low-dose CT for lung cancer. A number of potential barriers and technical challenges need to be overcome in order to implement such a programme. We discuss different approaches to MRI screening that could address these challenges, including abbreviated MRI protocols, targeted MRI screening, longer rescreening intervals and a multi-modal screening pathway. These approaches need further investigation, and we propose a phased stepwise research framework to ensure proper evaluation of the use of a fast MRI examination as a screening test for prostate cancer.
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Vernooij RW, Lancee M, Cleves A, Dahm P, Bangma CH, Aben KK. Radical prostatectomy versus deferred treatment for localised prostate cancer. Cochrane Database Syst Rev 2020; 6:CD006590. [PMID: 32495338 PMCID: PMC7270852 DOI: 10.1002/14651858.cd006590.pub3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Prostate cancer is a common cancer but is oftentimes slow growing. When confined to the prostate, radical prostatectomy (RP), which involves removal of the prostate, offers potential cure that may come at the price of adverse events. Deferred treatment, involving observation and palliative treatment only (watchful waiting (WW)) or close monitoring and delayed local treatment with curative intent as needed in the setting of disease progression (active monitoring (AM)/surveillance (AS)) might be an alternative. This is an update of a Cochrane Review previously published in 2010. OBJECTIVES To assess effects of RP compared with deferred treatment for clinically localised prostate cancer. SEARCH METHODS We searched the Cochrane Library (including CDSR, CENTRAL, DARE, and HTA), MEDLINE, Embase, AMED, Web of Science, LILACS, Scopus, and OpenGrey. Additionally, we searched two trial registries and conference abstracts of three conferences (EAU, AUA, and ASCO) until 3 March 2020. SELECTION CRITERIA We included all randomised controlled trials (RCTs) that compared RP versus deferred treatment in patients with localised prostate cancer, defined as T1-2, N0, M0 prostate cancer. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the eligibility of references and extracted data from included studies. The primary outcome was time to death from any cause; secondary outcomes were: time to death from prostate cancer; time to disease progression; time to metastatic disease; quality of life, including urinary and sexual function; and adverse events. We assessed the certainty of evidence per outcome using the GRADE approach. MAIN RESULTS: We included four studies with 2635 participants (average age between 60 to 70 years). Three multicentre RCTs, from Europe and USA, compared RP with WW (n = 1537), and one compared RP with AM (n = 1098). Radical prostatectomy versus watchful waiting RP probably reduces the risk of death from any cause (hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.70-0.90; 3 studies with 1537 participants; moderate-certainty evidence). Based on overall mortality at 29 years, this corresponds to 764 deaths per 1000 men in the RP group compared to 839 deaths per 1000 men in the WW group. RP probably also lowers the risk of death from prostate cancer (HR 0.57, 95% CI 0.44-0.73; 2 studies with 1426 participants; moderate-certainty evidence). Based on prostate cancer-specific mortality at 29 years, this corresponds to 195 deaths from prostate cancer per 1000 men in the RP group compared with 316 deaths from prostate cancer per 1000 men in the WW group. RP may reduce the risk of progression (HR 0.43, 95% CI 0.35-0.54; 2 studies with 1426 participants; I² = 54%; low-certainty evidence); at 19.5 years, this corresponds to 391 progressions per 1000 men for the RP group compared with 684 progressions per 1000 men for the WW group) and probably reduces the risk of developing metastatic disease (HR 0.56, 95% CI 0.46-0.70; 2 studies with 1426 participants; I² = 0%; moderate-certainty evidence); at 29 years, this corresponds to 271 metastatic diseases per 1000 men for RP compared with 431 metastatic diseases per 1000 men for WW. General quality of life at 12 years' follow-up is probably similar for both groups (risk ratio (RR) 1.0, 95% CI 0.85-1.16; low-certainty evidence), corresponding to 344 patients with high quality of life per 1000 men for the RP group compared with 344 patients with high quality of life per 1000 men for the WW group. Rates of urinary incontinence may be considerably higher (RR 3.97, 95% CI 2.34-6.74; low-certainty evidence), corresponding to 173 incontinent men per 1000 in the RP group compared with 44 incontinent men per 1000 in the WW group, as are rates of erectile dysfunction (RR 2.67, 95% CI 1.63-4.38; low-certainty evidence), corresponding to 389 erectile dysfunction events per 1000 for the RP group compared with 146 erectile dysfunction events per 1000 for the WW group, both at 10 years' follow-up. Radical prostatectomy versus active monitoring Based on one study including 1098 participants with 10 years' follow-up, there are probably no differences between RP and AM in time to death from any cause (HR 0.93, 95% CI 0.65-1.33; moderate-certainty evidence). Based on overall mortality at 10 years, this corresponds to 101 deaths per 1000 men in the RP group compared with 108 deaths per 1000 men in the AM group. Similarly, risk of death from prostate cancer probably is not different between the two groups (HR 0.63, 95% CI 0.21-1.89; moderate-certainty evidence). Based on prostate cancer-specific mortality at 10 years, this corresponds to nine prostate cancer deaths per 1000 men in the RP group compared with 15 prostate cancer deaths per 1000 men in the AM group. RP probably reduces the risk of progression (HR 0.39, 95% CI 0.27-0.56; moderate-certainty evidence; at 10 years, this corresponds to 86 progressions per 1000 men for RP compared with 206 progressions per 1000 men for AM) and the risk of developing metastatic disease (RR 0.39, 95% CI 0.21-0.73; moderate-certainty evidence; at 10 years, this corresponds to 24 metastatic diseases per 1000 men for the RP group compared with 61 metastatic diseases per 1000 men for the AM group).The general quality of life during follow-up was not different between the treatment groups. However, urinary function (mean difference (MD) 8.60 points lower, 95% CI 11.2-6.0 lower) and sexual function (MD 14.9 points lower, 95% CI 18.5-11.3 lower) on the Expanded Prostate Cancer Index Composite-26 (EPIC-26) instrument, were worse in the RP group. AUTHORS' CONCLUSIONS Based on long-term follow-up, RP compared with WW probably results in substantially improved oncological outcomes in men with localised prostate cancer but also markedly increases rates of urinary incontinence and erectile dysfunction. These findings are largely based on men diagnosed before widespread PSA screening, thereby limiting generalisability. Compared to AM, based on follow-up to 10 years, RP probably has similar outcomes with regard to overall and disease-specific survival yet probably reduces the risks of disease progression and metastatic disease. Urinary function and sexual function are probably decreased for the patients treated with RP.
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Affiliation(s)
- Robin Wm Vernooij
- Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands
| | - Michelle Lancee
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands
| | - Anne Cleves
- Velindre NHS Trust, Cardiff University Library Services, Cardiff, UK
| | - Philipp Dahm
- Urology Section, Minneapolis VA Health Care System, Minneapolis, Minnesota, USA
- Department of Urology, University of Minnesota, Minneapolis, Minnesota, USA
| | - Chris H Bangma
- Department of Urology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Katja Kh Aben
- Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands
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Royce PL, Ooi JJ, Sothilingam S, Yao HH. Survival and quality of life outcomes of high-intensity focused ultrasound treatment of localized prostate cancer. Prostate Int 2020; 8:85-90. [PMID: 32647645 PMCID: PMC7335960 DOI: 10.1016/j.prnil.2019.12.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 10/25/2019] [Accepted: 12/09/2019] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND To evaluate the survival and quality of life (QoL) outcomes of high-intensity focused ultrasound (HIFU) whole-gland ablation for localized prostate cancer. METHODS Over 8 years, men with localized prostate cancer treated with whole-gland HIFU were prospectively followed. Transrectal prostate ablation was performed under general anesthesia with Sonablate-500® (Sonacare Medical©, Charlotte, North Carolina, USA). The primary outcome was failure-free survival defined as no transition to any of the following: (1) local salvage therapy (surgery or radiotherapy), (2) systemic therapy, (3) metastases, or (4) prostate cancer-specific mortality. Secondary outcomes included both survival outcomes and QoL measures. RESULTS Of 70 men, 29.7% had International Society of Urological Pathology (ISUP) grade 1, 43.8% ISUP 2, 10.9% ISUP 3, and 15.6% ISUP 4 disease. At median follow-up of 83.4 months, overall mortality was 8.6% and prostate cancer-specific mortality 0%. Failure-free survival was 78.2% at 5 years and 71.2% at 7 years. Of all men, 7.1% of men developed metastases, with median metastasis-free survival of 75.4 months. There was negligible post-HIFU urinary incontinence or lower urinary tract symptom with a median Male Urogenital Distress Inventory score of 32 at 6 months and 33 at 12 months and median IPSS of 4 at 6 months and 3 at 12 months. Median Radiation Therapy Oncology Group rectal toxicity score was 0 throughout. In men who had mild or no erectile dysfunction at baseline (International Index of Erectile Function ≥17), the mean International Index of Erectile Function score declined to 37% from 23.5 at baseline to 14.7 at 12 months. CONCLUSION At median follow-up of 7 years, whole-gland HIFU appears to have comparable survival outcomes with other cohort studies involving radical prostatectomy and radiotherapy patient. It has low impact on QoL, preserved urinary continence, and erectile function approximate to nerve-sparing prostatectomy. Whole-gland HIFU presents a potential alternative minimally invasive and safe option for the treatment of localized prostate cancer.
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Affiliation(s)
- Peter L. Royce
- Department of Urology, Alfred Health, Melbourne, Victoria, Australia
- Urology Associates, Cabrini Health, Malvern, Victoria, Australia
| | - James J.Y. Ooi
- Department of Urology, Alfred Health, Melbourne, Victoria, Australia
| | | | - Henry H. Yao
- Department of Urology, Alfred Health, Melbourne, Victoria, Australia
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He L, Fang H, Wang X, Wang Y, Ge H, Li C, Chen C, Wan Y, He H. The 100 most-cited articles in urological surgery: A bibliometric analysis. Int J Surg 2020; 75:74-79. [PMID: 31926329 DOI: 10.1016/j.ijsu.2019.12.030] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/08/2019] [Accepted: 12/18/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND The purpose of this bibliometric analysis was to identify and assess the 100 most-cited articles (T100 articles) on urological surgery. METHODS The Web of Science (WoS) Core Collection database was used to investigate the T100 articles in the field of urological surgery. Different aspects of the T100 articles, including the countries, journals, authors, and topics, were analyzed. RESULTS The number of citations of T100 articles published between 1989 and 2016 ranged from 334 to 2189. The T100 articles originated from 28 countries, with more than half originating from the USA (n = 80). Professor Bill-Axelson A from Uppsala University Hospital published the largest number of T100 articles as the first author (4) and as a coauthor (1). The Memorial Sloan Kettering Cancer Center from the USA is the top institution with the most T100 articles in the field of urological surgery. The special journal Journal of Urology published 41 of the T100 articles, which had a total of 19780 citations. CONCLUSIONS Our study analyzed the 100 most-cited articles in the field of urological surgery. The USA is the dominant country in terms of the number of T100 articles, scientists and institutions. Surgery related to urological cancer has garnered the most academic attention, especially prostate cancer and renal cancer.
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Affiliation(s)
- Lugeng He
- Department of Urology, Affiliated Hangzhou First People'S Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, PR China.
| | - Hui Fang
- Institute of Information Resource, Zhejiang University of Technology, Hangzhou, 310014, PR China; Library, Zhejiang University of Technology, Hangzhou, 310014, PR China.
| | - Xuliang Wang
- Department of Urology, Affiliated Hangzhou First People'S Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, PR China.
| | - Yuyong Wang
- Department of Urology, Affiliated Hangzhou First People'S Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, PR China.
| | - Hongwei Ge
- Department of Urology, Affiliated Hangzhou First People'S Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, PR China.
| | - Changjiu Li
- Affiliated Hangzhou First People'S Hospital, Nanjing Medical University, Hangzhou, 310006, PR China.
| | - Chao Chen
- Department of Urology, Affiliated Hangzhou First People'S Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, PR China.
| | - Yuehua Wan
- Institute of Information Resource, Zhejiang University of Technology, Hangzhou, 310014, PR China; Library, Zhejiang University of Technology, Hangzhou, 310014, PR China.
| | - Huadong He
- Department of Urology, Affiliated Hangzhou First People'S Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, PR China.
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Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1. Cell Metab 2020; 31:105-114.e3. [PMID: 31564440 PMCID: PMC6949382 DOI: 10.1016/j.cmet.2019.08.024] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 07/11/2019] [Accepted: 08/30/2019] [Indexed: 01/17/2023]
Abstract
Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.
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Packer JR, Hirst AM, Droop AP, Adamson R, Simms MS, Mann VM, Frame FM, O'Connell D, Maitland NJ. Notch signalling is a potential resistance mechanism of progenitor cells within patient-derived prostate cultures following ROS-inducing treatments. FEBS Lett 2020; 594:209-226. [PMID: 31468514 PMCID: PMC7003772 DOI: 10.1002/1873-3468.13589] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 08/02/2019] [Accepted: 08/08/2019] [Indexed: 12/16/2022]
Abstract
Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, similarly to radiation. Radiation resistance results in tumour recurrence, however mechanisms of LTP resistance are unknown. LTP was applied to patient-derived prostate epithelial cells and gene expression assessed. A typical global oxidative response (AP-1 and Nrf2 signalling) was induced, whereas Notch signalling was activated exclusively in progenitor cells. Notch inhibition induced expression of prostatic acid phosphatase (PAP), a marker of prostate epithelial cell differentiation, whilst reducing colony forming ability and preventing tumour formation. Therefore, if LTP is to be progressed as a novel treatment for prostate cancer, combination treatments should be considered in the context of cellular heterogeneity and existence of cell type-specific resistance mechanisms.
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Affiliation(s)
- John R. Packer
- Cancer Research UnitDepartment of BiologyUniversity of YorkUK
| | - Adam M. Hirst
- Cancer Research UnitDepartment of BiologyUniversity of YorkUK
- Department of PhysicsYork Plasma InstituteUniversity of YorkUK
| | | | - Rachel Adamson
- Cancer Research UnitDepartment of BiologyUniversity of YorkUK
| | - Matthew S. Simms
- Department of UrologyCastle Hill Hospital (Hull and East Yorkshire Hospitals NHS Trust)CottinghamUK
| | - Vincent M. Mann
- Cancer Research UnitDepartment of BiologyUniversity of YorkUK
| | - Fiona M. Frame
- Cancer Research UnitDepartment of BiologyUniversity of YorkUK
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De Luca S, Fiori C, Tucci M, Poggio M, Allis S, Bollito E, Solitro F, Passera R, Buttigliero C, Porpiglia F. Prostate cancer management at an Italian tertiary referral center: does multidisciplinary team meeting influence diagnostic and therapeutic decision-making process? A snapshot of the everyday clinical practice. MINERVA UROL NEFROL 2019; 71:576-582. [DOI: 10.23736/s0393-2249.19.03231-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Hashimoto T, Nakashima J, Inoue R, Komori O, Yamaguchi Y, Kashima T, Satake N, Nakagami Y, Namiki K, Nagao T, Ohno Y. The significance of micro-lymphatic invasion and pathological Gleason score in prostate cancer patients with pathologically organ-confined disease and negative surgical margins after robot-assisted radical prostatectomy. Int J Clin Oncol 2019; 25:377-383. [PMID: 31673831 DOI: 10.1007/s10147-019-01561-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 10/06/2019] [Indexed: 12/01/2022]
Abstract
BACKGROUND The development process of recurrence in prostate cancer patients with pathologically organ-confined (pT2) disease and negative surgical margins is unclear. The aim of the present study was to determine factors associated with the development of biochemical recurrence following robot-assisted radical prostatectomy among those prostate cancer patients. METHODS We retrospectively reviewed the data of patients who underwent robot-assisted radical prostatectomy without neoadjuvant endocrine therapy. We evaluated prognostic factors in 1096 prostate cancer patients with pT2 disease and negative surgical margins. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for biochemical recurrence. RESULTS Of the 1096 patients, 55 experienced biochemical recurrence during the follow-up period. The 5-year biochemical recurrence-free survival rate for patients with pT2 and negative surgical margins was 91.8%. On univariate analysis, clinical stage, biopsy Gleason score, percent of positive core, pathological Gleason score, and the presence of micro-lymphatic invasion were significantly associated with biochemical recurrence. On a multivariate analysis, the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 were significant prognostic factors for biochemical recurrence. Based on these factors, we developed a risk stratification model. The biochemical recurrence-free survival rate differed significantly among the risk groups. CONCLUSIONS The prognosis of prostate cancer patients with pT2 disease and negative surgical margins is favorable. However, patients with the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 tend to experience biochemical recurrence more often after surgery. Therefore, careful follow-up might be necessary for those patients.
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Affiliation(s)
- Takeshi Hashimoto
- Department of Urology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
| | - Jun Nakashima
- Department of Urology, Sanno Hospital, Tokyo, Japan.,Clinical Medicine Research Center, International University of Health and Welfare, Tokyo, Japan
| | - Rie Inoue
- Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan
| | - Osamu Komori
- Department of Computer and Information Science, Seikei University, Tokyo, Japan.,School of Statistical Thinking, The Institute of Statistical Mathematics, Tachikawa, Tokyo, Japan
| | - Yuri Yamaguchi
- Department of Urology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Takeshi Kashima
- Department of Urology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Naoya Satake
- Department of Urology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Yoshihiro Nakagami
- Department of Urology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Kazunori Namiki
- Department of Urology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Toshitaka Nagao
- Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan
| | - Yoshio Ohno
- Department of Urology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
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Luo X, Yi M, Hu Q, Yin W. Prostatectomy Versus Observation for Localized Prostate Cancer: A Meta-Analysis. Scand J Surg 2019; 110:78-85. [PMID: 31662032 DOI: 10.1177/1457496919883962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND AIMS Controversy exists regarding whether prostatectomy benefits localized prostate cancer patients; the aim of our study was to evaluate the role of prostatectomy in localized prostate cancer patients. MATERIALS AND METHODS A systematic search was conducted using PubMed and Web of Science through March 22, 2019, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify randomized studies reporting on prostatectomy for localized prostate cancer patients. RESULTS Of a total of 1827 studies, six were considered for evidence synthesis. A total of 2524 patients in 3 studies were included for survival analysis, where 1256 patients received prostatectomy and 1268 patients received no treatment but were regularly followed up. Three other studies were included for adverse effects analysis. Prostatectomy displayed a significantly decreased risk of death of 9% compared with that of observation for patients with localized prostate cancer (risk ratio = 0.91; 95% confidence interval, 0.85-0.97; p = 0.007). Pooled data indicated that prostatectomy reduced the risk of disease progression by 43% (risk ratio = 0.57; 95% confidence interval, 0.47-0.70; p < 0.00001). Anxiety, depressed mood, well-being, and sense of meaningfulness for patients were not different between the prostatectomy and observation groups. However, prostatectomy increased the risk of erectile dysfunction by 2.10-fold (risk ratio = 2.10; 95% confidence interval, 1.36-3.26; p = 0.0009) and the risk of urinary function problems by 2.02-fold (risk ratio = 2.02; 95% confidence interval, 1.15-3.54; p = 0.01). CONCLUSION Prostatectomy prolonged survival and deferred disease progression compared to observation for patients with localized prostate cancer. Symptoms between the two groups were not significantly different except for erectile and urinary function. Patients should decide on prostatectomy after balancing the survival benefit and risk of erectile dysfunction.
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Affiliation(s)
- Xiaojin Luo
- Department of Urology, The People's Hospital of Yichun City, Yichun, China
| | - Meilian Yi
- Department of Nursing, The People's Hospital of Yichun City, Yichun, China
| | - Qun Hu
- Department of Anesthesia, The People's Hospital of Yichun City, Yichun, China
| | - Weihua Yin
- Department of Oncology, The People's Hospital of Yichun City, Yichun, China
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Ma W, Poon DM, Chan C, Chan T, Cheung F, Ho L, Lee EK, Leung AK, Leung SY, So H, Tam P, Kwong PW. Consensus statements on the management of clinically localized prostate cancer from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology. BJU Int 2019; 124:221-241. [PMID: 30653801 PMCID: PMC6850389 DOI: 10.1111/bju.14681] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To formulate consensus statements to facilitate physician management strategies for patients with clinically localized prostate cancer (PCa) in Hong Kong by jointly convening a panel of 12 experts from the two local professional organizations representing PCa specialists, who had previously established consensus statements on the management of metastatic PCa for the locality. METHODS Through a series of meetings, the panellists discussed their clinical experience and the published evidence regarding various areas of the management of localized PCa, then drafted consensus statements. At the final meeting, each drafted statement was voted on by every panellist based on its practicability of recommendation in the locality. RESULTS A total of 76 consensus statements were ultimately accepted and established by panel voting. CONCLUSION Derived from the recent evidence and major overseas guidelines, along with local clinical experience and practicability, the consensus statements were aimed to serve as a practical reference for physicians in Hong Kong for the management of localized PCa.
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Affiliation(s)
- Wai‐Kit Ma
- Department of SurgeryQueen Mary HospitalUniversity of Hong KongHong KongHong Kong
| | - Darren Ming‐Chun Poon
- State Key Laboratory in Oncology in South ChinaDepartment of Clinical OncologySir YK Pao Centre for CancerHong Kong Cancer Institute and Prince of Wales HospitalChinese University of Hong KongHong KongHong Kong
| | - Chi‐Kwok Chan
- Division of UrologyDepartment of SurgeryPrince of Wales HospitalChinese University of Hong KongHong KongHong Kong
| | - Tim‐Wai Chan
- Department of Clinical OncologyQueen Elizabeth HospitalHong KongHong Kong
| | | | | | - Eric Ka‐Chai Lee
- Department of Clinical OncologyTuen Mun HospitalHong KongHong Kong
| | | | | | - Hing‐Shing So
- Division of UrologyDepartment of SurgeryUnited Christian HospitalHong KongHong Kong
| | - Po‐Chor Tam
- Department of SurgeryQueen Mary HospitalThe University of Hong KongHong KongHong Kong
| | - Philip Wai‐Kay Kwong
- Department of Clinical OncologyQueen Mary HospitalUniversity of Hong KongHong Kong
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Kim K, Kwon H, Choi D, Lim T, Minn I, Son SH, Byun Y. Design and synthesis of dye-conjugated hepsin inhibitors. Bioorg Chem 2019; 89:102990. [DOI: 10.1016/j.bioorg.2019.102990] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 05/16/2019] [Accepted: 05/17/2019] [Indexed: 01/28/2023]
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Holze S, Mende M, Healy KV, Koehler N, Gansera L, Truss MC, Rebmann U, Degener S, Stolzenburg JU. Comparison of various continence definitions in a large group of patients undergoing radical prostatectomy: a multicentre, prospective study. BMC Urol 2019; 19:70. [PMID: 31345192 PMCID: PMC6659208 DOI: 10.1186/s12894-019-0500-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 07/18/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Due to the usage of various measurement methods and definitions, comparing continence rates after radical prostatectomy is a challenging task. This study compares continence rates based on different methods and aims to identify the definition for continence which agrees best with the patients' subjective assessment of continence. Additionally, continence was controlled for multiple influencing factors. METHODS This prospective multicentre study was carried out in seven hospitals throughout Germany. Before and at 3, 6, and 12 months after surgery self-reporting questionnaires were completed and returned by 329 (84.4%) of 390 eligible patients. The questionnaires were independently evaluated and analysed by a third party. Association of continence with demographic, operative, and tumour factors in an ongoing comprehensive prostate cancer database was evaluated. RESULTS The continence rate drops substantially for patients undergoing radical prostatectomy but increases again with time. Concrete numbers vary considerably depending on definition - 44% at 3 months and 68% at 12 months after surgery (0 pads) vs. 71 and 90% (0-1 pads). Significant confounding variables regarding continence rate are nerve-sparing procedure, categorized Gleason score, rehabilitative cure treatment, and pelvic floor training. The definition of 0 pads for continence coincides greater than 0-1 pads with the patients' self-assessment of being continent. CONCLUSION A standardized definition for continence would be desirable, as it is one of the most important preconditions to guarantee sound comparison of continence rates. Since there are enough other factors that make comparison difficult, we suggest using the definition of "0 pads". It is easily measured objectively, leaves no room for interpretation, and agrees best with the patients' self-assessment.
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Affiliation(s)
- Sigrun Holze
- Department of Urology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany.
| | - Meinhard Mende
- Coordination Centre for Clinical Trials, University of Leipzig, Härtelstr. 16-18, 04107, Leipzig, Germany
| | - Karl V Healy
- Department of Urology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany
| | - Norbert Koehler
- Department of Medical Psychology and Medical Sociology, University of Leipzig, Philipp-Rosenthal-Str. 55, 04103, Leipzig, Germany
| | - Lutz Gansera
- Department of Medical Psychology and Medical Sociology, University of Leipzig, Philipp-Rosenthal-Str. 55, 04103, Leipzig, Germany
| | - Michael C Truss
- Department of Urology, Klinikum Dortmund, Beurhausstr. 40, 44137, Dortmund, Germany
| | - Udo Rebmann
- Department of Urology, Diakonissenkrankenhaus Dessau, Gropiusallee 3, 06846, Dessau, Germany
| | - Stephan Degener
- Department of Urology, Helios Klinikum Wuppertal, Heusnerstr. 40, 42283, Wuppertal, Germany
| | - Jens-Uwe Stolzenburg
- Department of Urology, University of Leipzig, Liebigstr. 20, 04103, Leipzig, Germany
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García‐Barreras S, Sanchez‐Salas R, Mejia‐Monasterio C, Muttin F, Secin F, Dell'Oglio P, Nunes‐Silva I, Srougi V, Barret E, Rozet F, Prapotnich D, Cathelineau X. Biochemical recurrence‐free conditional probability after radical prostatectomy: A dynamic prognosis. Int J Urol 2019; 26:725-730. [DOI: 10.1111/iju.13982] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 03/21/2019] [Indexed: 11/27/2022]
Affiliation(s)
- Silvia García‐Barreras
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
| | - Rafael Sanchez‐Salas
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
| | - Carlos Mejia‐Monasterio
- Laboratory of Physical Properties School of Agricultural, Food and Biosystems Engineering Technical University of Madrid Madrid Spain
| | - Fabio Muttin
- Unit of Urology Division of Experimental Oncology Urological Research Institute IRCCS San Raffaele Scientific Institute Vita‐Salute San Raffaele University Milan Italy
| | - Fernando Secin
- Department of Urology CEMIC University Hospital Buenos Aires Argentina
| | - Paolo Dell'Oglio
- Unit of Urology Division of Experimental Oncology Urological Research Institute IRCCS San Raffaele Scientific Institute Vita‐Salute San Raffaele University Milan Italy
| | - Igor Nunes‐Silva
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
| | - Victor Srougi
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
| | - Eric Barret
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
| | - François Rozet
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
| | - Dominique Prapotnich
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
| | - Xavier Cathelineau
- Department of Urology Institute Mutualiste Montsouris Université Paris‐Descartes Paris France
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Gasinska A, Jaszczynski J, Rychlik U, Łuczynska E, Pogodzinski M, Palaczynski M. Prognostic Significance of Serum PSA Level and Telomerase, VEGF and GLUT-1 Protein Expression for the Biochemical Recurrence in Prostate Cancer Patients after Radical Prostatectomy. Pathol Oncol Res 2019; 26:1049-1056. [PMID: 30989489 PMCID: PMC7242245 DOI: 10.1007/s12253-019-00659-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 04/01/2019] [Indexed: 02/07/2023]
Abstract
The aim of the study was to evaluate prognosis for biochemical recurrence (BR) by analysing the pathological and biological characteristics of prostate cancer (PCa) after radical prostatectomy (RP). There were 130 men with clinically localized PCa in whom pretreatment serum PSA level and Ki-67, prostate specific membrane antigen (PSMA), glucose transporter-1 (GLUT-1), vascular endothelial growth factor (VEGF), microvessel density (MVD) and human telomerase reverse transcriptase (hTERT) proteins expression, based on number of immunohistochemically positive cells (labelling index), were retrospectively studied. In order to assess the prognostic significance of analysed variables in univariate and multivariate Cox analysis, patients were dichotomized based on cut-off points chosen by receiver operating characteristic (ROC) curves. There were 83 males (63.8%) at pT stage 1–2 and 47 (36.1%) at pT stage 3–4, respectively, with median (range) age of 62.8 years (49–77), and median follow-up of 78.5 months (12–148). In 42 (32.3%) men BR was found. In univariate analysis, tumour biological features: PSA ≤ 8 ng/mL (p = 0.006), Ki-67LI ≤ 12.7% (p = 0.015), VEGFLI>11.0% (p = 0.030), and hTERTLI>6.7% (p = 0.016), but not clinicopathological parameters, appeared to be positive prognosticators for BRFS. In the Cox analysis, Ki-67 lost its significance, and clinicopathological parameters appeared to be nonsignificant. The independent negative prognostic factors for BRFS were: PSA > 8.0 ng/mL, (Hazard ratio = 2.75, p = 0.003), GLUT-1 > 19.1% (HR = 2.1, p = 0.032), VEGF≤11.0% (HR = 1, p = 0.024) and hTERT≤6.7% (HR = 1, p = 0.017). High PSA level, and GLUT-1 expression and lower VEGF and nuclear hTERT expression may indicate the great role of hypoxia in BR induction in PCa.
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Affiliation(s)
- Anna Gasinska
- Department of Tumour Pathology, Oncology Center, Maria Sklodowska - Curie Institute, Cracow Branch, Garncarska 11, 31-115, Cracow, Poland.
| | - Janusz Jaszczynski
- Department of Surgery, Oncology Center, Maria Sklodowska - Curie Institute, Cracow Branch, Cracow, Poland
| | - Urszula Rychlik
- Department of Clinical Biochemistry, Oncology Center, Maria Sklodowska-Curie Institute, Cracow Branch, Cracow, Poland
| | - Elżbieta Łuczynska
- Department of Radiology, Oncology Center, Maria Sklodowska-Curie Institute, Cracow Branch, Cracow, Poland
| | - Marek Pogodzinski
- Department of Surgery, Oncology Center, Maria Sklodowska - Curie Institute, Cracow Branch, Cracow, Poland
| | - Mikolaj Palaczynski
- Department of Surgery, Oncology Center, Maria Sklodowska - Curie Institute, Cracow Branch, Cracow, Poland
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Brown LC, Ahmed HU, Faria R, El-Shater Bosaily A, Gabe R, Kaplan RS, Parmar M, Collaco-Moraes Y, Ward K, Hindley RG, Freeman A, Kirkham A, Oldroyd R, Parker C, Bott S, Burns-Cox N, Dudderidge T, Ghei M, Henderson A, Persad R, Rosario DJ, Shergill I, Winkler M, Soares M, Spackman E, Sculpher M, Emberton M. Multiparametric MRI to improve detection of prostate cancer compared with transrectal ultrasound-guided prostate biopsy alone: the PROMIS study. Health Technol Assess 2019; 22:1-176. [PMID: 30040065 DOI: 10.3310/hta22390] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Men with suspected prostate cancer usually undergo transrectal ultrasound (TRUS)-guided prostate biopsy. TRUS-guided biopsy can cause side effects and has relatively poor diagnostic accuracy. Multiparametric magnetic resonance imaging (mpMRI) used as a triage test might allow men to avoid unnecessary TRUS-guided biopsy and improve diagnostic accuracy. OBJECTIVES To (1) assess the ability of mpMRI to identify men who can safely avoid unnecessary biopsy, (2) assess the ability of the mpMRI-based pathway to improve the rate of detection of clinically significant (CS) cancer compared with TRUS-guided biopsy and (3) estimate the cost-effectiveness of a mpMRI-based diagnostic pathway. DESIGN A validating paired-cohort study and an economic evaluation using a decision-analytic model. SETTING Eleven NHS hospitals in England. PARTICIPANTS Men at risk of prostate cancer undergoing a first prostate biopsy. INTERVENTIONS Participants underwent three tests: (1) mpMRI (the index test), (2) TRUS-guided biopsy (the current standard) and (3) template prostate mapping (TPM) biopsy (the reference test). MAIN OUTCOME MEASURES Diagnostic accuracy of mpMRI, TRUS-guided biopsy and TPM-biopsy measured by sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using primary and secondary definitions of CS cancer. The percentage of negative magnetic resonance imaging (MRI) scans was used to identify men who might be able to avoid biopsy. RESULTS Diagnostic study - a total of 740 men were registered and 576 underwent all three tests. According to TPM-biopsy, the prevalence of any cancer was 71% [95% confidence interval (CI) 67% to 75%]. The prevalence of CS cancer according to the primary definition (a Gleason score of ≥ 4 + 3 and/or cancer core length of ≥ 6 mm) was 40% (95% CI 36% to 44%). For CS cancer, TRUS-guided biopsy showed a sensitivity of 48% (95% CI 42% to 55%), specificity of 96% (95% CI 94% to 98%), PPV of 90% (95% CI 83% to 94%) and NPV of 74% (95% CI 69% to 78%). The sensitivity of mpMRI was 93% (95% CI 88% to 96%), specificity was 41% (95% CI 36% to 46%), PPV was 51% (95% CI 46% to 56%) and NPV was 89% (95% CI 83% to 94%). A negative mpMRI scan was recorded for 158 men (27%). Of these, 17 were found to have CS cancer on TPM-biopsy. Economic evaluation - the most cost-effective strategy involved testing all men with mpMRI, followed by MRI-guided TRUS-guided biopsy in those patients with suspected CS cancer, followed by rebiopsy if CS cancer was not detected. This strategy is cost-effective at the TRUS-guided biopsy definition 2 (any Gleason pattern of ≥ 4 and/or cancer core length of ≥ 4 mm), mpMRI definition 2 (lesion volume of ≥ 0.2 ml and/or Gleason score of ≥ 3 + 4) and cut-off point 2 (likely to be benign) and detects 95% (95% CI 92% to 98%) of CS cancers. The main drivers of cost-effectiveness were the unit costs of tests, the improvement in sensitivity of MRI-guided TRUS-guided biopsy compared with blind TRUS-guided biopsy and the longer-term costs and outcomes of men with cancer. LIMITATIONS The PROstate Magnetic resonance Imaging Study (PROMIS) was carried out in a selected group and excluded men with a prostate volume of > 100 ml, who are less likely to have cancer. The limitations in the economic modelling arise from the limited evidence on the long-term outcomes of men with prostate cancer and on the sensitivity of MRI-targeted repeat biopsy. CONCLUSIONS Incorporating mpMRI into the diagnostic pathway as an initial test prior to prostate biopsy may (1) reduce the proportion of men having unnecessary biopsies, (2) improve the detection of CS prostate cancer and (3) increase the cost-effectiveness of the prostate cancer diagnostic and therapeutic pathway. The PROMIS data set will be used for future research; this is likely to include modelling prognostic factors for CS cancer, optimising MRI scan sequencing and biomarker or translational research analyses using the blood and urine samples collected. Better-quality evidence on long-term outcomes in prostate cancer under the various management strategies is required to better assess cost-effectiveness. The value-of-information analysis should be developed further to assess new research to commission. TRIAL REGISTRATION Current Controlled Trials ISRCTN16082556 and NCT01292291. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 39. See the NIHR Journals Library website for further project information. This project was also supported and partially funded by the NIHR Biomedical Research Centre at University College London (UCL) Hospitals NHS Foundation Trust and UCL and by The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research Biomedical Research Centre and was co-ordinated by the Medical Research Council's Clinical Trials Unit at UCL (grant code MC_UU_12023/28). It was sponsored by UCL. Funding for the additional collection of blood and urine samples for translational research was provided by Prostate Cancer UK.
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Affiliation(s)
- Louise Clare Brown
- Medical Research Council Clinical Trials Unit, University College London, London, UK
| | - Hashim U Ahmed
- Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London, UK.,Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Rita Faria
- Centre for Health Economics, University of York, York, UK
| | - Ahmed El-Shater Bosaily
- Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London, UK.,Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Rhian Gabe
- Hull York Medical School and Department of Health Sciences, University of York, York, UK
| | - Richard S Kaplan
- Medical Research Council Clinical Trials Unit, University College London, London, UK
| | - Mahesh Parmar
- Medical Research Council Clinical Trials Unit, University College London, London, UK
| | | | - Katie Ward
- Medical Research Council Clinical Trials Unit, University College London, London, UK
| | | | - Alex Freeman
- Department of Histopathology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Alexander Kirkham
- Department of Radiology, University College London Hospitals NHS Foundation Trust, London, UK
| | | | - Chris Parker
- Department of Academic Urology, Royal Marsden Hospital, Sutton, UK
| | | | | | | | - Maneesh Ghei
- Department of Urology, Whittington Hospital, London, UK
| | | | - Rajendra Persad
- Bristol Urological Institute, Southmead Hospital, Bristol, UK
| | | | | | | | - Marta Soares
- Centre for Health Economics, University of York, York, UK
| | - Eldon Spackman
- Centre for Health Economics, University of York, York, UK
| | - Mark Sculpher
- Centre for Health Economics, University of York, York, UK
| | - Mark Emberton
- Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London, UK.,Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK
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Skolarus TA, Metreger T, Wittmann D, Hwang S, Kim HM, Grubb RL, Gingrich JR, Zhu H, Piette JD, Hawley ST. Self-Management in Long-Term Prostate Cancer Survivors: A Randomized, Controlled Trial. J Clin Oncol 2019; 37:1326-1335. [PMID: 30925126 DOI: 10.1200/jco.18.01770] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
PURPOSE This randomized clinical trial compared a personally tailored, automated telephone symptom management intervention to improve self-management among long-term survivors of prostate cancer with usual care enhanced with a nontailored newsletter about symptom management. We hypothesized that intervention-group participants would have more confident symptom self-management and reduced symptom burden. METHODS A total of 556 prostate cancer survivors who, more than 1 year after treatment, were experiencing symptom burden were recruited from April 2015 to February 2017 across four Veterans Affairs sites. Participants were randomly assigned to intervention (n = 278) or usual care (n = 278) groups. We compared differences in the primary (symptom burden according to Expanded Prostate Cancer Index Composite-26 [EPIC], confidence in self-management) and secondary outcomes between groups using intent-to-treat analyses. We compared domain-specific changes in symptom burden from baseline to 5 and 12 months among the intervention group according to the primary symptom focus area (urinary, bowel, sexual, general) of participants. RESULTS Most of the prostate cancer survivors in this study were married (54.3%), were white (69.2%), were retired (62.4%), and underwent radiation therapy (56.7% v 46.2% who underwent surgery), and the mean age was 67 years. There were no baseline differences in urinary, bowel, sexual, or hormonal domain EPIC scores across groups. We observed higher EPIC scores in the intervention arm in all domain areas at 5 months, though differences were not statistically significant. No differences were found in secondary outcomes; however, coping appraisal was higher (2.8 v 2.6; P = .02) in intervention-arm patients at 5 months. In subgroup analyses, intervention participants reported improvement from baseline at 5 and 12 months in their symptom focus area domains. CONCLUSION This intervention was well received among veterans who were long-term survivors of prostate cancer. Although overall outcome differences were not observed across groups, the intervention tailored to symptom area of choice may hold promise to improve associated burden.
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Affiliation(s)
- Ted A Skolarus
- 1 Veterans Affairs Health Services Research and Development Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.,2 University of Michigan, Ann Arbor, MI
| | - Tabitha Metreger
- 1 Veterans Affairs Health Services Research and Development Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI
| | | | - Soohyun Hwang
- 3 University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC
| | - Hyungjin Myra Kim
- 1 Veterans Affairs Health Services Research and Development Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.,2 University of Michigan, Ann Arbor, MI
| | - Robert L Grubb
- 4 Medical University of South Carolina, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC
| | - Jeffrey R Gingrich
- 5 Duke University, Durham Veterans Affairs Healthcare System, Durham, NC
| | - Hui Zhu
- 6 Case Western Reserve University, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH
| | - John D Piette
- 1 Veterans Affairs Health Services Research and Development Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.,7 University of Michigan School of Public Health, Ann Arbor, MI
| | - Sarah T Hawley
- 1 Veterans Affairs Health Services Research and Development Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.,2 University of Michigan, Ann Arbor, MI
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Re: Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up. Eur Urol 2019; 75:1036. [PMID: 30826220 DOI: 10.1016/j.eururo.2019.02.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 02/14/2019] [Indexed: 12/24/2022]
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