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Ishikawa Y, Suzuki M, Yamaguchi H, Seto I, Machida M, Takagawa Y, Azami Y, Dai Y, Sulaiman NS, Teramura S, Narita Y, Kato T, Kikuchi Y, Fukaya Y, Murakami M. Real-world comparative outcomes and toxicities after definitive radiotherapy using proton beam therapy versus intensity-modulated radiation therapy for prostate cancer: a retrospective, single-institutional analysis. JOURNAL OF RADIATION RESEARCH 2025; 66:39-51. [PMID: 39812335 PMCID: PMC11753839 DOI: 10.1093/jrr/rrae065] [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: 05/02/2024] [Revised: 05/28/2024] [Indexed: 01/16/2025]
Abstract
This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A total of 606 patients diagnosed with prostate cancer between January 2008 and December 2018 were included. Of these patients, 510 received PBT up to a dose of 70-78 Gy (relative biological effectiveness) and 96 patients received IMRT up to a dose of 70-78 Gy. The median follow-up period was 82 months (range: 32-140 months). Patients in the PBT group had significantly higher 7-year rates of biochemical relapse-free survival (bRFS) and disease-free survival (DFS) rates: 95.1% for PBT vs 89.9% for IMRT (P = 0.0271) and 93.1% for PBT vs 85.0% for IMRT (P = 0.0019). After matching analysis, 94 patients were assigned to both groups, and the PBT group showed significantly higher 7-year bRFS and DFS rates: 98.9% for PBT vs 89.7% for IMRT (P = 0.023) and 93.4% for PBT vs 84.6% for IMRT (P = 0.022), respectively. In the subgroup analysis of intermediate-risk patients, the PBT group showed a significantly higher 7-year bRFS rate (98.3% for PBT vs 90.5% for IMRT; P = 0.007). The V60 of the bladder in the PBT group (18.1% ± 10.1%) was higher than that in the IMRT group (14.4% ± 7.6%) (P = 0.024). This study found that the treatment outcomes of PBT potentially surpassed those of IMRT specifically concerning bRFS and DFS in real-world settings. However, it should be noted that attention is warranted for late bladder complication of PBT.
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Affiliation(s)
- Yojiro Ishikawa
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
- Division of Radiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi 983-8536, Japan
| | - Motohisa Suzuki
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Hisashi Yamaguchi
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
| | - Ichiro Seto
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Masanori Machida
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Yoshiaki Takagawa
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
| | - Yusuke Azami
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Yuntao Dai
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Nor Shazrina Sulaiman
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Satoshi Teramura
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
- Division of Radiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi 983-8536, Japan
| | - Yuki Narita
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
| | - Takahiro Kato
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
- Department of Radiological Sciences, School of Health Sciences, Fukushima Medical University, 1 Hikariga-oka, Fukushima 960-1295, Japan
| | - Yasuyuki Kikuchi
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Yasuo Fukaya
- Department of Urology, Southern Tohoku Hospital, 7-172 Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
| | - Masao Murakami
- Department of Radiation Oncology, Southern Tohoku Proton Therapy Center 7-172, Yatsuyamada, Koriyama, Fukushima 963-8052, Japan
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Shah S, Pepin A, Jatar S, Hsueh J, Gallagher L, Danner MT, Zwart A, Ayoob M, Yung TM, Kumar D, Aghdam N, Leger PD, Dawson NA, Simeng S, Collins SP. Bothersome Hot Flashes Following Neoadjuvant Androgen Deprivation Therapy and Stereotactic Body Radiotherapy for Localized Prostate Cancer. Cureus 2024; 16:e55729. [PMID: 38586683 PMCID: PMC10998655 DOI: 10.7759/cureus.55729] [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] [Accepted: 03/06/2024] [Indexed: 04/09/2024] Open
Abstract
BACKGROUND Androgen deprivation therapy (ADT) improves local cancer control in unfavorable localized prostate cancer treated with radiotherapy. ADT is known to cause hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly burdensome. This study sought to evaluate the timeline of hot flashes following short-course ADT and stereotactic body radiotherapy (SBRT) as well as its relationship with testosterone recovery. METHODS Institutional IRB approval was obtained for this retrospective review of prospectively collected data (IRB#: 2009-510). ADT was initiated three months prior to the start of SBRT. Hot flashes were self-reported via question 13a of the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (one, three, six, nine, 12, 18, 24, and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem, and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up. RESULTS From 2007 to 2010, 122 localized prostate cancer patients (nine low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (three to six months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Thirty-two percent were Black and 27% were obese. Seventy-seven percent of patients received three months of ADT. At baseline, 2% of men experienced hot flashes that were a "moderate to big problem" and that proportion peaked at the start of SBRT (45%) before returning to baseline (2%) nine months post-SBRT with a cumulative incidence of 52.4%. The median baseline EPIC-26 hot flash score of 94 declined to 50 at the start of SBRT but this returned to baseline (92) by six months post SBRT. These changes were both statistically and clinically significant (MID = 9.5083, p<0.01). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. Resolution of hot flashes correlated with testosterone recovery. CONCLUSION Bothersome hot flashes occur in greater than 50% of men treated with neoadjuvant ADT. Resolution of hot flashes occurs in the majority of patients within one year after treatment. Reassurance of the temporary nature of hot flashes may assist in reducing patient anxiety. Measuring testosterone levels at follow-up visits may allow for anticipatory counseling that may limit the associated bother.
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Affiliation(s)
- Sarthak Shah
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Abigail Pepin
- Radiation Oncology, University of Pennsylvania Abramson Cancer Center, Philadelphia, USA
| | - Simran Jatar
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Jessica Hsueh
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Lindsey Gallagher
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Malika T Danner
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Alan Zwart
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Marilyn Ayoob
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Thomas M Yung
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Deepak Kumar
- Medicine, Biotechnology Research Institute, North Carolina Central University, Durham, USA
| | - Nima Aghdam
- Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Paul D Leger
- Oncology, MedStar Georgetown University Hospital, Washington, USA
| | - Nancy A Dawson
- Oncology, MedStar Georgetown University Hospital, Washington, USA
| | - Suy Simeng
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
| | - Sean P Collins
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, USA
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Shah S, Pepin A, Forsthoefel M, Burlile J, Collins BT, Simeng S, Aghdam N, Collins S. Testosterone as a Biomarker for Quality of Life (QOL) Following Androgen Deprivation Therapy (ADT) and Stereotactic Body Radiotherapy (SBRT). Cureus 2023; 15:e44440. [PMID: 37791195 PMCID: PMC10544092 DOI: 10.7759/cureus.44440] [Citation(s) in RCA: 4] [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: 08/31/2023] [Indexed: 10/05/2023] Open
Abstract
BACKGROUND Androgen deprivation therapy (ADT) causes fatigue and sexual dysfunction. The time to testosterone recovery depends on patient and treatment-specific characteristics. The kinetics of testosterone recovery in men treated with neoadjuvant ADT and stereotactic body radiotherapy (SBRT) is not well established. This study seeks to characterize testosterone recovery and evaluate its relationship with the improvement in patient-reported hormonal and sexual function. METHODS Institutional review board (IRB) approval was obtained for retrospective review of prospectively collected data. All patients with localized prostate cancer treated with short-course ADT (3-6 months of Leuprolide) and robotic SBRT (35-36.25 Gy in five fractions) at a single institution were included in this analysis. Testosterone levels were measured at the start of radiation, every 3 months for the first year, and every 6 months thereafter. Total testosterone recovery was defined as a serum level of >230 ng/dL. Sexual and hormonal function was recorded using the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of SBRT, and at each follow-up. The EPIC-26 subdomain scores were transformed to a 0-100 scale with higher scores reflecting less bother. RESULTS Between January 2009 and May 2018, 122 men with a median age of 72 years (range: 55-89 years) received ADT followed by SBRT. Thirty-two percent (N=39) were black and 27% [N=39 were obese (BMI > 30)]. The median pre-SBRT testosterone level was 15 ng/dL (range: 3-89 ng/dL). Around 77% (N=94) of patients received 3 months of ADT. The median pre-ADT EPIC-26 Hormone and Sexual Domain Scores were 94 and 41, respectively. At 12 months, 71% (N=87) of patients recovered to a eugonadal state with a mean recovery time of 4 months post-SBRT. Hormonal and sexual subdomain scores declined significantly following ADT but recovered to within the minimally important difference (MID) for sexual and hormonal domain scores by 12 months post-SBRT. CONCLUSIONS Testosterone recovery following short-course ADT with leuprolide and SBRT occurs rapidly in the majority of patients within one year after treatment. Quality of life domain improvements followed the testosterone recovery trend closely. Testosterone testing at follow-up appointments would allow for anticipatory counseling that may limit the bother associated with temporary quality of life decrements.
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Affiliation(s)
- Sarthak Shah
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, USA
| | - Abigail Pepin
- Radiation Oncology, University of Pennsylvania Abramson Cancer Center, Philadelphia, USA
| | - Matthew Forsthoefel
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, USA
| | | | - Brian T Collins
- Radiation Medicine, Tampa General Hospital (TGH) Cancer Institute, Tampa, USA
| | - Suy Simeng
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, USA
| | - Nima Aghdam
- Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Sean Collins
- Radiation Medicine, MedStar Georgetown University Hospital, Washington, DC, USA
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The Clinical Cell-Cycle Risk (CCR) Score Is Associated With Metastasis After Radiation Therapy and Provides Guidance on When to Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation. Int J Radiat Oncol Biol Phys 2022; 113:66-76. [PMID: 34610388 DOI: 10.1016/j.ijrobp.2021.09.034] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 09/20/2021] [Accepted: 09/25/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis. RESULTS The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%. CONCLUSIONS The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis.
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Post CM, Kahn JM, Turina CB, Beer TM, Hung AY. Short-term ADT and Dose-escalated IMRT in Patients With Intermediate-risk Prostate Cancer: Benefit or Caution? Am J Clin Oncol 2022; 45:190-195. [PMID: 35446278 DOI: 10.1097/coc.0000000000000908] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES In the era of dose-escalated prostate radiation therapy (RT), the use of androgen deprivation therapy (ADT) is undefined for intermediate-risk (IR) prostate cancer. There is growing concern of the risk of ADT to be detrimental to quality of life. This single-institution retrospective analysis aimed to evaluate outcomes of IR patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with or without concurrent/adjuvant short-term ADT. MATERIALS AND METHODS Data was collected from 260 consecutive patients treated with dose-escalated IMRT with daily image-guided RT for newly diagnosed IR prostate cancer. Biochemical recurrence-free survival (BCRFS), distant metastasis-free survival, prostate cancer-specific survival, and overall survival (OS) were calculated using Kaplan-Meier methodology. RESULTS Median follow-up was 93 months. A total of 181 patients had unfavorable IR disease, and 36.2% (N=94) received ADT, with median ADT duration of 6 months. Seven-year BCRFS was 94.1% vs. 86.2% (P=0.067), for ADT and no ADT, respectively, and no difference in distant metastasis-free survival or prostate cancer-specific survival was observed. ADT was associated with significantly worse 7-year OS (80.0% vs. 91.3%, P=0.010). Analysis of the unfavorable IR cohort alone, showed similar results; 7-year BCRFS and 7-year OS in patients who received ADT versus no ADT were 93.7% vs. 85.9% (P=0.093), and 79.0% vs. 90.6% (P=0.019), respectively. CONCLUSIONS In our 15-year experience treating IR prostate cancer with dose-escalated IMRT with daily image-guided RT, short-term concurrent ADT was associated with a statistically significant worse OS. Additional studies are needed to determine if ADT is beneficial or detrimental for patients with IR prostate cancer treated with dose-escalated radiation.
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Affiliation(s)
| | | | | | - Tomasz M Beer
- Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR
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Sasamura K, Soyano T, Kozuka T, Yuasa T, Yamamoto S, Yonese J, Oguchi M, Yoshimura R, Yoshioka Y. Outcomes of intensity-modulated radiation therapy for intermediate- or high-risk prostate cancer: a single-institutional study. Jpn J Clin Oncol 2022; 52:170-178. [PMID: 34689189 DOI: 10.1093/jjco/hyab167] [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: 07/08/2021] [Accepted: 10/07/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND There are few reports from Japan about the outcomes of intensity-modulated radiation therapy for localized prostate cancer. This study was aimed at assessing the efficacy and toxicity of intensity-modulated radiation therapy in patients with intermediate- or high-risk prostate cancer. METHODS We conducted a review of the data, retrieved from our institutional database, of patients who had received intensity-modulated radiation therapy for localized prostate cancer at a radiation dose of 78 Gy in 39 fractions. Data of 201 patients with intermediate-risk prostate cancer and 311 patients with high-risk prostate cancer were analyzed. RESULTS The median follow-up period after the completion of intensity-modulated radiation therapy was 100 months (range, 24-154). The rates of cause-specific survival, overall survival, metastasis-free survival and biochemical recurrence-free survival in the intermediate-risk patients were 99, 95, 95 and 94% at 5 years and 99, 91, 90 and 86% at 8 years, respectively; the corresponding rates in the high-risk patients were 100, 97, 91 and 84% at 5 years and 96, 92, 84 and 76% at 8 years, respectively. The crude incidence of late grade 2-3 genitourinary toxicity was 28.1%, and that of late grade 3 genitourinary toxicity was 2.0%. The crude incidence of late grade 2 gastrointestinal toxicity was 5.1%, and there were no cases of late grade 3 gastrointestinal toxicity. CONCLUSIONS Our data demonstrated that intensity-modulated radiation therapy is effective for patients with localized intermediate-risk or high-risk prostate cancer while having minimal toxicity.
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Affiliation(s)
- Kazuma Sasamura
- Radiation Oncology Department, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.,Department of Radiation Therapeutics and Oncology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takashi Soyano
- Department of Radiology, Japan Self-Defense Forces Central Hospital, Tokyo, Japan
| | - Takuyo Kozuka
- Department of Radiology, University of Tokyo Hospital, Tokyo, Japan
| | - Takeshi Yuasa
- Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shinya Yamamoto
- Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Junji Yonese
- Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masahiko Oguchi
- Radiation Oncology Department, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Ryoichi Yoshimura
- Department of Radiation Therapeutics and Oncology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuo Yoshioka
- Radiation Oncology Department, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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Li G, Li Y, Wang J, Gao X, Zhong Q, He L, Li C, Liu M, Liu Y, Ma M, Wang H, Wang X, Zhu H. Guidelines for radiotherapy of prostate cancer (2020 edition). PRECISION RADIATION ONCOLOGY 2021. [DOI: 10.1002/pro6.1129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Affiliation(s)
- Gaofeng Li
- Department of Radiation Oncology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing P. R. China
| | - Yexiong Li
- State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing P. R. China
| | - Junjie Wang
- Department of Radiation Oncology Peking University Third Hospital Beijing P. R. China
| | - Xianshu Gao
- Department of Radiation Oncology Peking University First Hospital Beijing P. R. China
| | - Qiuzi Zhong
- Department of Radiation Oncology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing P. R. China
| | - Liru He
- Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. China
| | - Chunmei Li
- Department of Radiation Oncology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing P. R. China
| | - Ming Liu
- Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing P. R. China
| | - Yueping Liu
- State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC) Beijing P. R. China
| | - Mingwei Ma
- Department of Radiation Oncology Peking University First Hospital Beijing P. R. China
| | - Hao Wang
- Department of Radiation Oncology Peking University Third Hospital Beijing P. R. China
| | - Xuan Wang
- Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing P. R. China
| | - Hui Zhu
- Department of Nuclear Medicine Department, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing P. R. China
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Kollmeier MA, McBride S, Gorovets D, Zelefsky MJ. Role of Androgen-Deprivation Therapy Remains Uncertain for Intermediate-Risk Patients When Using Dose-Escalated Radiotherapy. J Clin Oncol 2020; 38:3821-3822. [PMID: 32997577 DOI: 10.1200/jco.20.02105] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Marisa A Kollmeier
- Marisa A. Kollmeier, MD; Sean McBride, MD, MPH; Daniel Gorovets, MD; and Michael J. Zelefsky, MD, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Sean McBride
- Marisa A. Kollmeier, MD; Sean McBride, MD, MPH; Daniel Gorovets, MD; and Michael J. Zelefsky, MD, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Daniel Gorovets
- Marisa A. Kollmeier, MD; Sean McBride, MD, MPH; Daniel Gorovets, MD; and Michael J. Zelefsky, MD, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Michael J Zelefsky
- Marisa A. Kollmeier, MD; Sean McBride, MD, MPH; Daniel Gorovets, MD; and Michael J. Zelefsky, MD, Memorial Sloan Kettering Cancer Center, New York, NY
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9
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Spratt DE, Tward JD. Absolute versus Relative Benefit of Androgen Deprivation Therapy for Prostate Cancer: Moving Beyond the Hazard Ratio to Personalize Therapy. Int J Radiat Oncol Biol Phys 2020; 108:899-902. [PMID: 32928598 DOI: 10.1016/j.ijrobp.2020.06.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 05/19/2020] [Accepted: 06/04/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Daniel E Spratt
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
| | - Jonathan D Tward
- Department of Radiation Oncology, Huntsman Cancer Center, Salt Lake City, Utah
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10
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Mendez LC, Martell K, Warner A, Tseng CL, Chung H, Loblaw A, Rodrigues GB, Morton G. Does ADT benefit unfavourable intermediate risk prostate cancer patients treated with brachytherapy boost and external beam radiotherapy? A propensity-score matched analysis. Radiother Oncol 2020; 150:195-200. [PMID: 32619455 DOI: 10.1016/j.radonc.2020.06.039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 06/23/2020] [Accepted: 06/24/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. MATERIAL AND METHODS Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan-Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. RESULTS A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4-6) and delivered a median time of 2.7 months (IQR: 1.7-4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. CONCLUSION Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.
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Affiliation(s)
- Lucas C Mendez
- Division of Radiation Oncology, London Health Sciences Centre, London, Canada
| | - Kevin Martell
- Department of Oncology, University of Calgary, Canada
| | - Andrew Warner
- Division of Radiation Oncology, London Health Sciences Centre, London, Canada
| | - Chia-Lin Tseng
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Hans Chung
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Andrew Loblaw
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - George B Rodrigues
- Division of Radiation Oncology, London Health Sciences Centre, London, Canada
| | - Gerard Morton
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada.
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11
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Optimal Androgen Deprivation Therapy Combined with Proton Beam Therapy for Prostate Cancer: Results from a Multi-Institutional Study of the Japanese Radiation Oncology Study Group. Cancers (Basel) 2020; 12:cancers12061690. [PMID: 32630494 PMCID: PMC7352923 DOI: 10.3390/cancers12061690] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 06/19/2020] [Accepted: 06/23/2020] [Indexed: 12/24/2022] Open
Abstract
Background: Androgen deprivation therapy (ADT) combined with radiation therapy benefits intermediate- and high-risk prostate cancer (PC) patients. The optimal ADT duration in combination with high-dose proton beam therapy (PBT) remains unknown. Methods: Intermediate- and high-risk PC patients treated with PBT combined with ADT for various durations were analyzed retrospectively. To assess the relationship between ADT and biochemical relapse-free (bRF) rate, Cox proportional hazards models including T stage, prostate specific antigen (PSA) level, Gleason score (GS), and total radiation dose were used. Results: In the intermediate-risk PC patients (n = 520), ADT use improved bRF (HR 0.49, 95% CI 0.26–0.93; p = 0.029), especially in those with multiple intermediate-risk factors (T2b–2c, PSA 10–20 ng/mL, and GS 7). In the high-risk PC patients (n = 555), a longer ADT duration (>6 months) conferred a benefit for bRF (HR 0.54, 95% CI 0.32–0.90; p = 0.018), which was most apparent in patients with multiple high-risk factors (T3a–4, PSA > 20 ng/mL, and GS ≥ 8) treated with ADT for ≥21 months. Conclusions: Short-term (≤6 months) ADT is beneficial for intermediate-risk PC patients, but likely unnecessary for those with a single risk factor, whereas ADT for >6 months is necessary for high-risk PC patients and ADT for ≥21 months might be optimal for those with multiple risk factors in combination of high-dose PBT.
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12
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Roy S, Malone S. Reply to P. Ghadjar et al. J Clin Oncol 2020; 38:1747-1748. [DOI: 10.1200/jco.20.00280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Soumyajit Roy
- Soumyajit Roy, MBBS, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD; The Ottawa Hospital Regional Cancer Center, Ottawa, Ontario, Canada; Shawn Malone, MD, The Ottawa Hospital Regional Cancer Center, Ottawa, Ontario, Canada; and Division of Radiation Oncology, Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Shawn Malone
- Soumyajit Roy, MBBS, Radiation Oncology Branch, National Cancer Institute, Bethesda, MD; The Ottawa Hospital Regional Cancer Center, Ottawa, Ontario, Canada; Shawn Malone, MD, The Ottawa Hospital Regional Cancer Center, Ottawa, Ontario, Canada; and Division of Radiation Oncology, Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada
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13
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Pettersson A, Alm D, Garmo H, Hjelm Eriksson M, Castellanos E, Åström L, Kindblom J, Widmark A, Gunnlaugsson A, Franck Lissbrant I, Nilsson P, Stattin P. Comparative Effectiveness of Different Radical Radiotherapy Treatment Regimens for Prostate Cancer: A Population-Based Cohort Study. JNCI Cancer Spectr 2020; 4:pkaa006. [PMID: 32373776 PMCID: PMC7192027 DOI: 10.1093/jncics/pkaa006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 01/09/2020] [Accepted: 02/07/2020] [Indexed: 02/07/2023] Open
Abstract
Background It is unclear which radiotherapy technique and dose fractionation scheme is most effective in decreasing the risk of prostate cancer death. Methods We conducted a population-based cohort study among 15 164 men in the Prostate Cancer database Sweden (version 4.0) treated with primary radical radiotherapy for prostate cancer in Sweden from 1998 to 2016. We calculated hazard ratios with 95% confidence intervals (CIs) of the association between the following exposure groups and outcome: conventionally fractionated external beam radiotherapy (EBRT) to 78 Gy (39 × 2 Gy), EBRT combined with high dose-rate brachytherapy (HDR-BT) (25 × 2 Gy + 2 × 10 Gy), conventionally fractionated EBRT to 70 Gy (35 × 2 Gy), and moderately hypofractionated (M-HF) dose-escalated EBRT (29 × 2.5 Gy or 22 × 3 Gy). Results Of the men, 7296 received conventionally fractionated EBRT to 78 Gy, 4657 EBRT combined with HDR-BT, 1672 conventionally fractionated EBRT to 70 Gy, and 1539 M-HF EBRT. Using EBRT to 78 Gy as the reference, the multivariable hazard ratios (95% CIs) of prostate cancer death was 0.64 (0.53 to 0.78) for EBRT combined with HDR-BT, 1.00 (0.80 to 1.27) for EBRT to 70 Gy, and 1.51 (0.99 to 2.32) for M-HF EBRT. The multivariable hazard ratios (95% CIs) for death from any cause were 0.79 (0.71 to 0.88), 0.99 (0.87 to 1.14), and 1.12 (0.88 to 1.42), respectively. The lower risk of prostate cancer death comparing EBRT combined with HDR-BT with conventionally fractionated EBRT to 78 Gy was more pronounced for men with high-risk or poorly differentiated tumors. Conclusions In this study, EBRT combined with HDR-BT was the most effective radiotherapy treatment regimen, especially for poorly differentiated tumors. Randomized trials comparing EBRT combined with HDR-BT with dose-escalated EBRT should be a priority.
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Affiliation(s)
- Andreas Pettersson
- Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Daniel Alm
- Department of Radiation Oncology, Karolinska University Hospital, Stockholm, Sweden
| | - Hans Garmo
- Regional Cancer Centre Uppsala Örebro, Uppsala University Hospital, Uppsala, Sweden.,Cancer Epidemiology Group, Division of Cancer Studies, School of Medicine, King's College London, London, UK
| | | | | | - Lennart Åström
- Section of Clinical and Experimental Oncology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Jon Kindblom
- Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Anders Widmark
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Adalsteinn Gunnlaugsson
- Department of Oncology and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden
| | - Ingela Franck Lissbrant
- Department of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Per Nilsson
- Department of Oncology and Radiation Physics, Skåne University Hospital, Lund University, Lund, Sweden
| | - Pär Stattin
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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14
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Role of combined radiation and androgen deprivation therapy in intermediate-risk prostate cancer. Strahlenther Onkol 2019; 196:109-116. [DOI: 10.1007/s00066-019-01553-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 11/14/2019] [Indexed: 02/07/2023]
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15
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Amit U, Lawrence YR, Weiss I, Symon Z. Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer? Radiat Oncol 2019; 14:99. [PMID: 31182119 PMCID: PMC6558831 DOI: 10.1186/s13014-019-1298-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Accepted: 05/15/2019] [Indexed: 11/22/2022] Open
Abstract
Objective Androgen deprivation therapy (ADT) is beneficial for unfavorable intermediate-risk (IR) prostate cancer patients receiving curative radiotherapy (RT). However, for favorable IR patients the latest NCCN guidelines recommends RT alone. We retrospectively studied treatment patterns and outcomes of patients with IR prostate cancer in our institution over the past two decades. Materials and methods Three hundred seventy-three IR prostate cancer patients treated with definitive RT between 5/2002–5/2016 were identified in an institutional review board approved database. All patients received conformal RT to the prostate while the vast majority did not receive nodal radiation. ADT was commenced 2 months prior to RT and was continued for 4 months after RT. Results Compared to RT alone, patients receiving combined RT+ ADT had more positive biopsy cores, higher pre-radiation PSA, more IR factors, and were more likely to receive pelvic lymph node radiation. However, there were no differences in failure either biochemical, local or distal, nor on survival between the favorable RT alone and the unfavorable RT+ ADT cohorts, suggesting a beneficial role for ADT. On multivariate analysis, patients 70 years or younger receiving RT alone were at increased risk for biochemical failure during a 6-year follow-up (HR 3.06, P = 0.025). Biochemical relapse free survival in patients ≤70 years who received RT alone was 82.1% vs 94.0% for RT + ADT (P = 0.030). There was no difference for combined treatment modality in patients > 70 years (P = 0.87). Conclusions Men 70 years or younger with favorable IR prostate cancer treated with RT alone to 78 Gy are at increased risk of biochemical failure. Short term ADT should be considered in this cohort of men. Electronic supplementary material The online version of this article (10.1186/s13014-019-1298-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Uri Amit
- Radiation Oncology Department, Chaim Sheba Medical Center, Tel-Hashomer, Israel. .,The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
| | - Yaacov R Lawrence
- Radiation Oncology Department, Chaim Sheba Medical Center, Tel-Hashomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ilana Weiss
- Radiation Oncology Department, Chaim Sheba Medical Center, Tel-Hashomer, Israel
| | - Zvi Symon
- Radiation Oncology Department, Chaim Sheba Medical Center, Tel-Hashomer, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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16
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Ghadjar P, Wiegel T. Optimizing radiotherapy for intermediate-risk localized disease. Nat Rev Urol 2018; 15:470-471. [DOI: 10.1038/s41585-018-0024-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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17
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Arimura T, Yoshiura T, Matsukawa K, Kondo N, Kitano I, Ogino T. Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study. Cancers (Basel) 2018; 10:cancers10040116. [PMID: 29642619 PMCID: PMC5923371 DOI: 10.3390/cancers10040116] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 04/05/2018] [Accepted: 04/06/2018] [Indexed: 11/16/2022] Open
Abstract
The role of proton beam therapy (PBT) as monotherapy for localized prostate cancer (PCa) remains unclear. The purpose of this study was to evaluate the efficacy and adverse events of PBT alone for these patients. Between January 2011 and July 2014, 218 patients with intermediate- and high-risk PCa who declined androgen deprivation therapy (ADT) were enrolled to the study and were treated with PBT following one of the following protocols: 74 Gray (GyE) with 37 fractions (fr) (74 GyE/37 fr), 78 GyE/39 fr, and 70 GyE/28 fr. The 5-year progression-free survival rate in the intermediate- and high-risk groups was 97% and 83%, respectively (p = 0.002). The rate of grade 2 or higher late gastrointestinal toxicity was 3.9%, and a significant increased incidence was noted in those who received the 78 GyE/39 fr protocol (p < 0.05). Grade 2 or higher acute and late genitourinary toxicities were observed in 23.5% and 3.4% of patients, respectively. Our results indicated that PBT monotherapy can be a beneficial treatment for localized PCa. Furthermore, it can preserve the quality of life of these patients. We believe that this study provides crucial hypotheses for further study and for establishing new treatment strategies.
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Affiliation(s)
- Takeshi Arimura
- Medipolis Proton Therapy and Research Center, 4233 Higashikata, Ibusuki, Kagoshima 8910304, Japan.
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 8908520, Japan.
| | - Takashi Yoshiura
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 8908520, Japan.
| | - Kyoko Matsukawa
- Medipolis Proton Therapy and Research Center, 4233 Higashikata, Ibusuki, Kagoshima 8910304, Japan.
| | - Naoaki Kondo
- Medipolis Proton Therapy and Research Center, 4233 Higashikata, Ibusuki, Kagoshima 8910304, Japan.
| | - Ikumi Kitano
- Medipolis Proton Therapy and Research Center, 4233 Higashikata, Ibusuki, Kagoshima 8910304, Japan.
| | - Takashi Ogino
- Medipolis Proton Therapy and Research Center, 4233 Higashikata, Ibusuki, Kagoshima 8910304, Japan.
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18
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Aljubran A, Abusamra A, Alkhateeb S, Alotaibi M, Rabah D, Bazarbashi S, Alkushi H, Al-Mansour M, Alharbi H, Eltijani A, Alghamdi A, Alsharm A, Ahmad I, Murshid E. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for prostate cancer 2017. Urol Ann 2018; 10:138-145. [PMID: 29719323 DOI: 10.4103/ua.ua-177-17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
This is an update to the previously published Saudi guidelines for the evaluation and medical and surgical management of patients diagnosed with prostate cancer. Prostate cancer is categorized according to the stage of the disease using the tumor node metastasis staging system 7th edition. The guidelines are presented with supporting evidence levels based on a comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Local factors, such as availability, logistic feasibility, and familiarity of various treatment modalities, have been taken into consideration. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with adenocarcinoma of the prostate.
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Affiliation(s)
- Ali Aljubran
- Oncology Center, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Ashraf Abusamra
- Department of Surgery, Urology Section, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Sultan Alkhateeb
- Department of Surgery, Division of Urology, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohammed Alotaibi
- Department of Urology, King Faisal Specialist Hospital and Research Center, Dammam, Saudi Arabia
| | - Danny Rabah
- Department of Surgery, College of Medicine and Uro-Oncology Research Chair, King Saud University, Dammam, Saudi Arabia
| | - Shouki Bazarbashi
- Oncology Center, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hussain Alkushi
- Department of Pathology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mubarak Al-Mansour
- Department of Oncology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Hulayel Alharbi
- Department of Medical Oncology, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Amin Eltijani
- Department of Oncology, Division of Medical Oncology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abdullah Alghamdi
- Department of Urology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Abdullah Alsharm
- Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Imran Ahmad
- Department of Oncology, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
| | - Esam Murshid
- Department of Oncology, Oncology Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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19
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Abstract
PURPOSE OF REVIEW Androgen deprivation therapy (ADT) is an important adjunctive therapy to external beam radiation therapy (RT) for the definitive management of prostate cancer. The role of ADT is well-established for locally advanced or high-risk disease in conjunction with standard doses of RT, but less defined for intermediate-risk disease or with dose-escalated RT. The goal of this review is to summarize evidence evaluating the combination of ADT/RT, focusing on recent trials and current controversies as they pertain to the practicing clinician. RECENT FINDINGS The benefit of ADT on biochemical control is maintained with dose-escalated RT according to recently reported phase III studies. Furthermore, there is now prospective, randomized evidence to support the addition of ADT to RT in the post-prostatectomy setting. ADT continues to play an important role for prostate cancer patients receiving dose-escalated RT. Future research is needed to identify subgroups most likely to benefit from this combination.
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20
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Pryor DI, Turner SL, Tai KH, Tang C, Sasso G, Dreosti M, Woo HH, Wilton L, Martin JM. Moderate hypofractionation for prostate cancer: A user's guide. J Med Imaging Radiat Oncol 2018; 62:232-239. [PMID: 29336109 DOI: 10.1111/1754-9485.12703] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 12/12/2017] [Indexed: 01/16/2023]
Abstract
Three large randomised controlled trials have been published in the last year demonstrating the non-inferiority of moderate hypofractionation compared to conventional fractionation for localised prostate cancer with respect to both disease control and late toxicity at 5 years. Furthermore, no clinically significant differences in patient-reported outcomes have emerged. More mature follow-up data are now also available from phase 2 studies confirming that moderate hypofractionation is associated with low rates of significant toxicity at 10 years. Moving forward it is likely that appropriate patient selection, integration of androgen deprivation and attention to optimising technique will play a more important role than modest differences in dose-fractionation schedules. Here we briefly review the evidence, discuss issues of patient selection and provide an approach to implementing moderately hypofractionated radiation therapy for prostate cancer in clinical practice.
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Affiliation(s)
- David I Pryor
- Princess Alexandra Hospital, Brisbane, Queensland, Australia.,APCRC-Q, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Sandra L Turner
- Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia.,University of Sydney, Camperdown, New South Wales, Australia
| | - Keen Hun Tai
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.,University of Melbourne, Melbourne, Victoria, Australia
| | - Colin Tang
- Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Giuseppe Sasso
- Auckland City Hospital, Auckland, New Zealand.,University of Auckland, Auckland, New Zealand
| | - Marcus Dreosti
- Genesis Cancer Care, Adelaide, South Australia, Australia
| | - Henry H Woo
- Sydney Adventist Hospital Clinical School, University of Sydney, Sydney, New South Wales, Australia
| | - Lee Wilton
- Calvary Mater Newcastle, Waratah, New South Wales, Australia
| | - Jarad M Martin
- Calvary Mater Newcastle, Waratah, New South Wales, Australia.,School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
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21
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Aljubran A, Abusamra A, Alkhateeb S, Alotaibi M, Rabah D, Bazarbashi S, Alkushi H, Al-Mansour M, Alharbi H, Eltijani A, Alghamdi A, Alsharm A, Ahmad I, Murshid E. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for prostate cancer 2017. Urol Ann 2018; 10:138-145. [PMID: 29719323 PMCID: PMC5907320 DOI: 10.4103/ua.ua_177_17] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
This is an update to the previously published Saudi guidelines for the evaluation and medical and surgical management of patients diagnosed with prostate cancer. Prostate cancer is categorized according to the stage of the disease using the tumor node metastasis staging system 7th edition. The guidelines are presented with supporting evidence levels based on a comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi Oncology Society and Saudi Urological Association. Local factors, such as availability, logistic feasibility, and familiarity of various treatment modalities, have been taken into consideration. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health-care policymakers in the management of patients diagnosed with adenocarcinoma of the prostate.
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Affiliation(s)
- Ali Aljubran
- Oncology Center, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Ashraf Abusamra
- Department of Surgery, Urology Section, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Sultan Alkhateeb
- Department of Surgery, Division of Urology, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mohammed Alotaibi
- Department of Urology, King Faisal Specialist Hospital and Research Center, Dammam, Saudi Arabia
| | - Danny Rabah
- Department of Surgery, College of Medicine and Uro-Oncology Research Chair, King Saud University, Dammam, Saudi Arabia
| | - Shouki Bazarbashi
- Oncology Center, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hussain Alkushi
- Department of Pathology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mubarak Al-Mansour
- Department of Oncology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Hulayel Alharbi
- Department of Medical Oncology, King Fahad Specialist Hospital, Dammam, Saudi Arabia
| | - Amin Eltijani
- Department of Oncology, Division of Medical Oncology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abdullah Alghamdi
- Department of Urology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Abdullah Alsharm
- Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Imran Ahmad
- Department of Oncology, Section of Medical Oncology, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia
| | - Esam Murshid
- Department of Oncology, Oncology Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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22
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Ong WL, Foroudi F, Evans S, Millar J. Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer. BJU Int 2017; 120 Suppl 3:35-42. [DOI: 10.1111/bju.13969] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Wee Loon Ong
- Department of Radiation Oncology; Olivia Newton-John Cancer and Wellness Centre, Austin Health; Heidelberg Vic. Australia
- Department of Epidemiology and Preventive Medicine; Monash University; Melbourne Vic. Australia
| | - Farshad Foroudi
- Department of Radiation Oncology; Olivia Newton-John Cancer and Wellness Centre, Austin Health; Heidelberg Vic. Australia
| | - Sue Evans
- Department of Epidemiology and Preventive Medicine; Monash University; Melbourne Vic. Australia
| | - Jeremy Millar
- Alfred Health Radiation Oncology Services; Prahran Vic. Australia
- Central Clinical School; Monash University; Melbourne Vic. Australia
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23
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Choong ES, Hruby G, Yang J, Kwong C, Patanjali N. 78Gy with Fiducial Marker Image-Guided Radiotherapy in Prostate Cancer: Single Center Analysis of 301 Patients. Asia Pac J Clin Oncol 2016; 13:e356-e363. [PMID: 27863019 DOI: 10.1111/ajco.12637] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 09/02/2016] [Indexed: 12/31/2022]
Abstract
AIM In prostate cancer, fiducial marker image-guided radiotherapy (FMIGRT) allows correction of setup errors and interfraction physiological motion resulting in improved accuracy of target and sparing of at risk organs. We aim to report outcomes and toxicities observed in patients treated with dose escalation to 78Gy with FMIGRT in our center. METHODS AND MATERIALS Retrospective review of consecutive patients with histologically confirmed T1-4N0M0 localized prostate cancer treated with dose escalation to 78Gy with FMIGRT in our center. All patients had 3-D conformal radiotherapy. Duration of androgen deprivation therapy use was tailored to risk group. Toxicity was scored according to CTCAE.v04. Kaplan-Meier analysis was performed for freedom from biochemical failure (FFBF), prostate cancer-specific survival and overall survival. RESULTS Median follow-up was 48.6 months. Median duration of androgen deprivation therapy was 6 and 23 months in the intermediate- and high-risk group, respectively. FFBF at 5 years was 88.8%. FFBFs when stratified to risk groups were 100% for low risk, 88.9% for low-intermediate risk, 89.9% for high-intermediate risk and 85.4% for high risk, respectively. Acute severe toxicity (grade≥3) rate for both genitourinary (GU) and gastrointestinal (GI) was 1%. Late moderate-to-severe toxicity (grade≥2) rates for GU and GI were 15% and 17%, respectively, with severe (grade≥3) toxicity rate for GU and GI at 2% and 3%, respectively. CONCLUSION Dose escalation to 78Gy with FMIGRT in our series achieved good FFBF at 5 years with low acute and late toxicity rates. These results provide a good comparator cohort to our current use of image-guided intensity modulated radiotherapy.
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Affiliation(s)
- Ee Siang Choong
- Department of Radiation Oncology, Chris O'Brien Lifehouse, Camperdown, Sydney, New South Wales, Australia
| | - George Hruby
- Department of Radiation Oncology, Royal North Shore Hospital, St Leonards, Sydney, New South Wales, Australia
| | - Jean Yang
- School of Mathematics and Statistics, University of Sydney, Sydney, New South Wales, Australia
| | - Carol Kwong
- Department of Radiation Oncology, Chris O'Brien Lifehouse, Camperdown, Sydney, New South Wales, Australia
| | - Nitya Patanjali
- Department of Radiation Oncology, Chris O'Brien Lifehouse, Camperdown, Sydney, New South Wales, Australia
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24
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Chiang PH, Liu YY. Comparisons of oncological and functional outcomes among radical retropubic prostatectomy, high dose rate brachytherapy, cryoablation and high-intensity focused ultrasound for localized prostate cancer. SPRINGERPLUS 2016; 5:1905. [PMID: 27867812 PMCID: PMC5095104 DOI: 10.1186/s40064-016-3584-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Accepted: 09/14/2016] [Indexed: 11/10/2022]
Abstract
PURPOSE To conduct a retrospective, single institutional and comparative study for radical retropubic prostatectomy (RRP), high dose rate brachytherapy (HDRBT), cryoablation and high-intensity focused ultrasound (HIFU) in localized prostate cancer with respect to oncological and functional outcomes. METHODS We reviewed 97, 161, 114 and 120 patients of RRP, HDRBT, cryoablation and HIFU respectively for localized prostate cancer from May 2008 to December 2013. PSA biochemical recurrence, salvage treatment-free rate, metastasis-free rate, and biochemical recurrence-free survival were analyzed for oncological outcomes. Functional outcomes included complications and serial IIEF-5 scores, IPSS and related QoL scores. RESULTS During nearly 3 years of follow-up, the patients of HDRBT experienced higher PSA biochemical recurrence rate overall (54.7%), as well as D'Amico intermediate-risk (34.4%) and high-risk (61.8%) groups, lower salvage treatment-free rate (46.7%), and metastasis-free rate (90.7%). Besides, the patients of RRP demonstrated higher urethral stricture (29.9%) and urinary incontinence (11.3%). The patients of HIFU revealed lower de novo erectile dysfunction rate at 1 year (65.6%), higher serial IIEF-5 scores, lower IPSS and related QoL scores. CONCLUSIONS The patients of HDRBT demonstrated worse oncological outcomes in D'Amico intermediate and high-risk groups. Besides, the patients of RRP had more complications rate in urethral stricture and urinary incontinence. Moreover, the patients of HIFU experienced better urinary function improvement and more possible sexual function preservation. In consideration of trifecta, HIFU may provide equivalent cancer control and better quality of life for patients of localized prostate cancer.
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Affiliation(s)
- Po Hui Chiang
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd, Niaosong District, Kaohsiung City, 833 Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Yi Yang Liu
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd, Niaosong District, Kaohsiung City, 833 Taiwan.,College of Medicine, Chang Gung University, Taoyuan City, Taiwan
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Bian SX, Kuban DA, Levy LB, Oh J, Choi S, McGuire SE, Frank SJ, Mahmood U, Nguyen PL, Pugh TJ, Lee AK, Hoffman KE. The Influence of Age and Comorbidity on the Benefit of Adding Androgen Deprivation to Dose-escalated Radiation in Men With Intermediate-risk Prostate Cancer. Am J Clin Oncol 2016; 39:368-73. [PMID: 24732810 DOI: 10.1097/coc.0000000000000071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE Androgen deprivation therapy (ADT) can improve outcomes for men with intermediate-risk prostate cancer (IR-PrCa) receiving external-beam radiotherapy (EBRT). Older men and men with significant comorbidity may be more susceptible to the harms of ADT, therefore we aimed to determine whether these men benefit from ADT. METHODS The adult comorbidity evaluation-27 index categorized severity of comorbidity in 636 men treated for IR-PrCa with dose-escalated EBRT (>75 Gy). The cohort was dichotomized at median age of 70. Multivariate Cox proportional hazard analysis evaluated the association of ADT with failure-free survival (FFS) for each age and comorbidity subgroup. RESULTS A total of 48% of men were 70 years and above. After adjustment for tumor characteristics, the addition of ADT to EBRT was associated with improved FFS for both men below 70 years of age (adjusted hazard ratio [AHR] 0.44; 95% confidence interval [CI], 0.19-0.99; P=0.046) and men 70 years and above (AHR 0.23; 95% CI, 0.06-0.91; P=0.035). ADT improved FFS for men below 70 years who had no or mild comorbidity (AHR 0.25; 95% CI, 0.09-0.73; P=0.011) but not for men below 70 years who had moderate or severe comorbidity (AHR 1.62; 95% CI, 0.35-7.49; P=0.537). Similarly, in men 70 years and above, there was a trend for improved FFS with ADT in healthy men (AHR 0.10; 95% CI, 0.01-1.08; P=0.058) but not in men with moderate to severe comorbidity (AHR 0.38; 95% CI, 0.06-2.56; P=0.318). CONCLUSIONS The addition of ADT to dose-escalated EBRT can improve outcomes for both younger and older men with IR-PrCa. This benefit was more pronounced in healthy men.
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Affiliation(s)
- Shelly X Bian
- Departments of *Radiation Oncology †Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX ‡Department of Radiation Oncology, Dana Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston MA
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Bracci S, Osti MF, Agolli L, Bertaccini L, De Sanctis V, Valeriani M. Different outcomes among favourable and unfavourable intermediate-risk prostate cancer patients treated with hypofractionated radiotherapy and androgen deprivation therapy. Radiat Oncol 2016; 11:78. [PMID: 27276878 PMCID: PMC4898326 DOI: 10.1186/s13014-016-0656-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 06/01/2016] [Indexed: 12/29/2022] Open
Abstract
Background to evaluate the role of a risk stratification system in intermediate-risk prostate cancer (PCa) treated with hypofractionated radiotherapy (HyRT). Methods 131 patients affected by intermediate-risk PCa were treated with HyRT at the total dose of 54,75 Gy in 15 fraction plus 9 months of androgen deprivation therapy (ADT). Patients were classified as favourable risk (FIR) if they had a single NCCN intermediate-risk factor (IRF), a Gleason score ≤3 + 4 = 7, and <50 % of biopsy cores containing cancer (PBCC). If these criteria were not met were classified as unfavourable risk (UIR). Univariate and multivariate analyses using Cox proportional hazards model were calculated for biochemical recurrence-free survival (bRFS), the risk of local recurrence and metastasis-free survival (MFS). Results After a median follow-up of 56.7 months (range 9.8 to 93.7 months), 11 patients (8.4 %) died, of whom 2 (1.5 %) for PCa. In the univariate analysis, Gleason score, PPBCs, IRFs and PSA at first follow-up were prognostic factors for bRFS and LF while Gleason score, PPBCs and PSA at first follow-up were significant predictor for MFS. In the multivariate analysis only the PSA at first follow-up resulted a prognostic factor for bRFS and MFS. Patients with a value of PSA at first follow-up <0.7 ng/mL respect to those with PSA ≥0,7 ng/mL had a 5y-bRFS of 93.3 % vs. 57.5 %, 5y-MFS of 99.0 % vs. 78.9 % and 5y-LF of 5.8 % vs. 38.3 %. Patients in the UIR PCa group with a PSA value <0.7 ng/mL at first follow-up had significant better bRFS, LF and MFS. Conclusions Risk factors currently not included in the guidelines are useful to stratify patients with intermediate-risk PCa in two groups of different prognosis even when HyRT is delivered. PSA at first follow-up is useful in UIR PCa to guide the overall length of ADT.
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Affiliation(s)
- Stefano Bracci
- Institute of Radiation Oncology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy.
| | - Mattia F Osti
- Institute of Radiation Oncology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Linda Agolli
- Institute of Radiation Oncology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Luca Bertaccini
- Institute of Radiation Oncology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Vitaliana De Sanctis
- Institute of Radiation Oncology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
| | - Maurizio Valeriani
- Institute of Radiation Oncology, Sant'Andrea Hospital, Via di Grottarossa 1035-1039, 00189, Rome, Italy
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Schmid M, Meyer CP, Reznor G, Choueiri TK, Hanske J, Sammon JD, Abdollah F, Chun FKH, Kibel AS, Tucker-Seeley RD, Kantoff PW, Lipsitz SR, Menon M, Nguyen PL, Trinh QD. Racial Differences in the Surgical Care of Medicare Beneficiaries With Localized Prostate Cancer. JAMA Oncol 2016; 2:85-93. [PMID: 26502115 DOI: 10.1001/jamaoncol.2015.3384] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
IMPORTANCE There is extensive evidence suggesting that black men with localized prostate cancer (PCa) have worse cancer-specific mortality compared with their non-Hispanic white counterparts. OBJECTIVE To evaluate racial disparities in the use, quality of care, and outcomes of radical prostatectomy (RP) in elderly men (≥ 65 years) with nonmetastatic PCa. DESIGN, SETTING, AND PARTICIPANTS This retrospective analysis of outcomes stratified according to race (black vs non-Hispanic white) included 2020 elderly black patients (7.6%) and 24,462 elderly non-Hispanic white patients (92.4%) with localized PCa who underwent RP within the first year of PCa diagnosis in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2009. The study was performed in 2014. MAIN OUTCOMES AND MEASURES Process of care (ie, time to treatment, lymph node dissection), as well as outcome measures (ie, complications, emergency department visits, readmissions, PCa-specific and all-cause mortality, costs) were evaluated using Cox proportional hazards regression. Multivariable conditional logistic regression and quantile regression were used to study the association of racial disparities with process of care and outcome measures. RESULTS The proportion of black patients with localized prostate cancer who underwent RP within 90 days was 59.4% vs 69.5% of non-Hispanic white patients (P < 001). In quantile regression of the top 50% of patients, blacks had a 7-day treatment delay compared with non-Hispanic whites. (P < 001). Black patients were less likely to undergo lymph node dissection (odds ratio [OR], 0.76 [95% CI, 0.66-0.80]; P < .001) but had higher odds of postoperative visits to the emergency department (within 30 days: OR, 1.48 [95% CI, 1.18-1.86]); after 30 days or more (OR, 1.45 [95% CI, 1.19-1.76]) and readmissions (within 30 days: OR, 1.28 [95% CI, 1.02-1.61]); ≥ 30 days (OR, 1.27 [95% CI, 1.07-1.51]) compared with non-Hispanic whites. The surgical treatment of black patients was associated with a higher incremental annual cost (the top 50% of blacks spent $1185.50 (95% CI , $804.85-1 $1566.10; P < .001) more than the top 50% of non-Hispanic whites). There was no difference in PCa-specific mortality (P = .16) or all-cause mortality (P = .64) between black and non-Hispanic white men. CONCLUSIONS AND RELEVANCE Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared with non-Hispanic white men; however, this does not translate into a difference in PCa-specific or all-cause mortality.
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Affiliation(s)
- Marianne Schmid
- Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts2Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christian P Meyer
- Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts2Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gally Reznor
- Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Toni K Choueiri
- Dana-Farber Cancer Institute, Department of Medical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Julian Hanske
- Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jesse D Sammon
- Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan
| | - Firas Abdollah
- Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan
| | - Felix K H Chun
- Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Adam S Kibel
- Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Reginald D Tucker-Seeley
- Center for Community-Based Research, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Philip W Kantoff
- Dana-Farber Cancer Institute, Department of Medical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Stuart R Lipsitz
- Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Mani Menon
- Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan
| | - Paul L Nguyen
- Dana-Farber Cancer Institute, Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Quoc-Dien Trinh
- Center for Surgery and Public Health, Division of Urologic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Zilli T, Dal Pra A, Kountouri M, Miralbell R. Prognostic value of biochemical response to neoadjuvant androgen deprivation before external beam radiotherapy for prostate cancer: A systematic review of the literature. Cancer Treat Rev 2016; 46:35-41. [DOI: 10.1016/j.ctrv.2016.03.016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Revised: 03/28/2016] [Accepted: 03/30/2016] [Indexed: 10/22/2022]
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Abusamra A, Murshid E, Kushi H, Alkhateeb S, Al-Mansour M, Saadeddin A, Rabah D, Bazarbashi S, Alotaibi M, Alghamdi A, Alghamdi K, Alsharm A, Ahmad I. Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer. Urol Ann 2016; 8:123-130. [PMID: 27141178 PMCID: PMC4839225 DOI: 10.4103/0974-7796.176872] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Accepted: 11/15/2015] [Indexed: 02/05/2023] Open
Abstract
This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with prostate cancer. It is categorized according to the stage of the disease using the tumor node metastasis staging system 7(th) edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors) who were selected by the Saudi oncology society and Saudi urological association. Considerations to the local availability of drugs, technology, and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with adenocarcinoma of the prostate to.
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Affiliation(s)
- Ashraf Abusamra
- Department of Surgery, Urology Section, King Khalid Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Esam Murshid
- Department of Oncology, Oncology Center, Prince Sultan Medical Military City, Riyadh, Saudi Arabia
| | - Hussain Kushi
- Department of Radiation Oncology, Princess Norah Oncology Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Sultan Alkhateeb
- Department of Surgery, Division of Urology, King Abdulaziz Medical City and King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Mubarak Al-Mansour
- Department of Oncology, King Abdulaziz Medical City and King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Ahmad Saadeddin
- Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Danny Rabah
- Department of Surgery, College of Medicine and Uro-Oncology Research Chair, King Saud University, Riyadh, Saudi Arabia
| | - Shouki Bazarbashi
- Department of Oncology, Section of Medical Oncology, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Mohammed Alotaibi
- Department of Urology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdullah Alghamdi
- Department of Urology, Prince Sultan Medical Military Center, Riyadh, Saudi Arabia
| | - Khalid Alghamdi
- Department of Surgery, Division of Urology, Security Forces Hospital, Riyadh, Saudi Arabia
| | - Abdullah Alsharm
- Department of Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Imran Ahmad
- Department of Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
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Bellefqih S, Hadadi K, Mezouri I, Maghous A, Marnouche E, Andaloussi K, Elmarjany M, Sifat H, Mansouri H, Benjaafar N. Association de radiothérapie et d’hormonothérapie dans la prise en charge des cancers localisés de la prostate : où en est-on ? Cancer Radiother 2016; 20:141-50. [DOI: 10.1016/j.canrad.2015.12.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Revised: 12/21/2015] [Accepted: 12/24/2015] [Indexed: 12/12/2022]
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Survival outcomes of radiotherapy with or without androgen-deprivation therapy for patients with intermediate-risk prostate cancer using the National Cancer Data Base. Urol Oncol 2016; 34:165.e1-9. [DOI: 10.1016/j.urolonc.2015.11.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Revised: 11/03/2015] [Accepted: 11/10/2015] [Indexed: 11/22/2022]
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Amini A, Jones BL, Jackson MW, Rusthoven CG, Maroni P, Kavanagh BD, Raben D. Survival outcomes of combined external beam radiotherapy and brachytherapy vs. brachytherapy alone for intermediate-risk prostate cancer patients using the National Cancer Data Base. Brachytherapy 2016; 15:136-46. [DOI: 10.1016/j.brachy.2015.11.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 11/21/2015] [Accepted: 11/30/2015] [Indexed: 10/22/2022]
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Baker BR, Mohiuddin JJ, Chen RC. Radiation with Hormonal Therapy. Prostate Cancer 2016. [DOI: 10.1016/b978-0-12-800077-9.00043-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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Amini A, Kavanagh BD, Rusthoven CG. Improved survival with the addition of radiotherapy to androgen deprivation: questions answered and a review of current controversies in radiotherapy for non-metastatic prostate cancer. ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:14. [PMID: 26855950 PMCID: PMC4716946 DOI: 10.3978/j.issn.2305-5839.2015.10.13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Accepted: 09/25/2015] [Indexed: 11/14/2022]
Abstract
The contemporary standard of care for locally advanced high-risk prostate cancer includes a combination of dose-escalated radiotherapy (RT) plus androgen-deprivation therapy (ADT). However, 20 years ago, at the inception of the National Cancer Institute of Canada (NCIC) led study (NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110), the survival impact of prostate RT for high-risk disease was uncertain. Recently, Mason, Warde and colleagues presented the final results of this NCIC/MRC study (PMID: 25691677) randomizing 1,205 high-risk prostate cancer patients to ADT + RT vs. ADT alone. These updated results confirm substantial improvements with the addition of RT to ADT for the endpoints of overall survival (OS), disease-free survival (DFS), and biochemical recurrence. Close examination of subtleties of this trial's design highlight some of the most salient controversies in the field of prostate RT, including the risk-stratified roles of ADT, optimal ADT duration, and RT field design in the dose-escalated and intensity-modulated radiotherapy (IMRT) era.
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Affiliation(s)
- Arya Amini
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Brian D Kavanagh
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Chad G Rusthoven
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA
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Tsumura H, Satoh T, Ishiyama H, Hirano S, Tabata KI, Kurosaka S, Matsumoto K, Fujita T, Kitano M, Baba S, Hayakawa K, Iwamura M. Recovery of serum testosterone following neoadjuvant and adjuvant androgen deprivation therapy in men treated with prostate brachytherapy. World J Radiol 2015; 7:494-500. [PMID: 26753064 PMCID: PMC4697123 DOI: 10.4329/wjr.v7.i12.494] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Revised: 08/13/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the time course of testosterone (T) recovery after cessation of androgen deprivation therapy (ADT) in patients treated with brachytherapy.
METHODS: One-hundred and seventy-four patients treated between June 1999 and February 2009 were studied. Patients were divided into a short-term usage group (≤ 12 mo, n = 91) and a long-term usage group (≥ 36 mo, n = 83) according to the duration of gonadotropin-releasing hormone agonist therapy. Median follow-up was 29 mo in the short-term group and was 60 mo in the long-term group.
RESULTS: Cumulative incidence rates of T recovery to normal and supracastrate levels at 24 mo after cessation were 28.8% and 74.6%, respectively, in the long-term usage group, whereas these values were 96.4% and 98.8% in the short-term usage group. T recovery to normal and supracastrate levels occurred significantly more rapidly in the short-term than in the long-term usage group (P < 0.001 and P < 0.001, respectively). Five years after cessation, 22.6% of patients maintained a castrate T level in the long-term usage group. On multivariate analysis, lower T levels (< 10 ng/dL) at cessation of ADT was significantly associated with prolonged T recovery to supracastrate levels in the long-term usage group (P = 0.002).
CONCLUSION: Lower T levels at cessation of ADT were associated with prolonged T recovery in the long-term usage group. Five years after cessation of long-term ADT, approximately one-fifth of patients still had castrate T levels. When determining the therapeutic effect, especially biochemical control, we should consider this delay in T recovery.
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Guidance on patient consultation. Current evidence for prostate-specific antigen screening in healthy men and treatment options for men with proven localised prostate cancer. Curr Urol Rep 2015; 16:28. [PMID: 25773347 DOI: 10.1007/s11934-015-0502-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The main objective of this review is to summarise, for primary and secondary care doctors, the management options and current supporting evidence for clinically localised prostate cancer. We review all aspects of management including current guidelines on early cancer detection and the importance of informed consent on PSA-based screening and assess the most common treatment options and the evidence for managing patients with low-, medium-, and high-risk disease.
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Kohutek ZA, Weg ES, Pei X, Shi W, Zhang Z, Kollmeier MA, Zelefsky MJ. Long-term Impact of Androgen-deprivation Therapy on Cardiovascular Morbidity After Radiotherapy for Clinically Localized Prostate Cancer. Urology 2015; 87:146-52. [PMID: 26476405 DOI: 10.1016/j.urology.2015.08.029] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 06/29/2015] [Accepted: 08/04/2015] [Indexed: 10/22/2022]
Abstract
OBJECTIVE To characterize the impact of androgen-deprivation therapy (ADT) on the incidence of cardiovascular events (CE) in prostate cancer patients treated with radiotherapy (RT). MATERIALS AND METHODS There were 2211 patients with localized prostate cancer treated with RT from 1988 to 2008 at our institution. There were 991 patients (44.8%) who received ADT at the time of RT for a median of 6.1 months. Salvage ADT was initiated prior to CE in 365 men (16.5%) at a median of 5.5 years (range: 0.6 to 18.4 years) after RT and continued for a median of 4.3 years. A nomogram was constructed to predict the 10-year risk of CE "post-RT" (i.e., after RT). RESULTS Patients receiving ADT at the time of RT exhibited significantly higher 10-year incidence of CE (19.6%, 95% CI 17.0%-22.6%) than those not receiving ADT (14.3%, 95% CI 12.2%-16.7%, P = .005). On multivariate analysis, both ADT at the time of RT (P = .007) and the time of salvage (P = .0004) were associated with increased CE risk, as were advanced age (P = .02), smoking (P = .0007), history of diabetes (P = .0007), and history of CE before RT (P < .0001). A nomogram using patient age, smoking status, history of pre-RT CE, history of diabetes, and ADT use at the time of RT predicted the rate of 10-year CE with a C-index of 0.81 (95% CI, 0.72-0.88). CONCLUSION While ADT is often an essential part of prostate cancer treatment, patients should be counseled regarding increased risks of CE and prophylactic efforts should be considered to mitigate that risk.
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Affiliation(s)
- Zachary A Kohutek
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Emily S Weg
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Xin Pei
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Weiji Shi
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Zhigang Zhang
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Marisa A Kollmeier
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Michael J Zelefsky
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
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Voog JC, Paulus R, Efstathiou JA. Reply from Authors re: Ronald C. Chen. Decisions Regarding Whether to Use Androgen Deprivation Therapy with Radiotherapy in Prostate Cancer: Is Cardiovascular Mortality the Most Relevant Outcome? Eur Urol 2016;69:211-2: Outcomes for Favorable and Unfavorable Intermediate Risk Prostate Cancer Patients Receiving Radiation Therapy With or Without Short-term Androgen Deprivation Therapy. Eur Urol 2015; 69:212-3. [PMID: 26443430 DOI: 10.1016/j.eururo.2015.09.030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 09/18/2015] [Indexed: 10/22/2022]
Affiliation(s)
| | - Rebecca Paulus
- NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA
| | - Jason A Efstathiou
- Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA,.
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Occult High-risk Disease in Clinically Low-risk Prostate Cancer with ≥50% Positive Biopsy Cores: Should National Guidelines Stop Calling Them Low Risk? Urology 2015; 87:125-32. [PMID: 26391387 DOI: 10.1016/j.urology.2015.08.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 07/25/2015] [Accepted: 08/18/2015] [Indexed: 11/21/2022]
Abstract
OBJECTIVE To identify contemporary, clinically low-risk patients with ≥50% cores positive and compare the risk of upgrading at prostatectomy with other low- or intermediate-risk patients. MATERIALS AND METHODS We studied 14,902 patients with prostate cancer in the Surveillance, Epidemiology, and End Results database in 2010-2011 treated with prostatectomy. Patients were categorized by National Comprehensive Cancer Network clinical risk groups, separating low-risk patients by percent positive biopsy cores (PBC). We measured incidence of pathologic high-risk disease, defined as pT3a-T4 or Gleason 8-10, and multivariable logistic regression was used to determine if patients with clinical low-risk disease and ≥50% PBC were similar to other low- or intermediate-risk patients. This analysis was repeated with favorable and unfavorable intermediate risk. RESULTS At prostatectomy, 9.2% of clinically low-risk patients with <50% PBC, 18.6% of clinically low-risk patients with ≥50% PBC, and 27.6% of clinically intermediate-risk patients had occult, high-risk disease (P <.001). On multivariable logistic regression, low-risk patients with ≥50% PBC were more likely than low-risk patients with <50% PBC to have pathologic high-risk disease (adjusted odds ratio [AOR] 2.28, 95% confidence interval 1.90-2.73, P <.001), had similar risk to favorable intermediate patients overall (AOR 1.09, 0.91-1.31, P = .33), and had higher risk than favorable intermediate patients aged over 60 years (AOR 1.28, 1.00-1.64, P = .04). Low-risk patients with ≥50% PBC had a mean tumor size similar to unfavorable intermediate-risk patients (21.3 vs 21.0 mm, P = .82). CONCLUSION Nearly 1 in 5 clinically low-risk prostate cancer patients with ≥50% PBC harbor occult pT3a-T4 or Gleason 8-10, suggesting that national guidelines should not classify low-risk patients with ≥50% cores positive as "low risk," and patients should be made aware of this excess risk if considering active surveillance.
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Locke JA, Dal Pra A, Supiot S, Warde P, Bristow RG. Synergistic action of image-guided radiotherapy and androgen deprivation therapy. Nat Rev Urol 2015; 12:193-204. [PMID: 25800395 DOI: 10.1038/nrurol.2015.50] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.
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Affiliation(s)
- Jennifer A Locke
- Department of Urologic Sciences, University of British Columbia, Gordon &Leslie Diamond Health Care Centre, Level 6, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada
| | - Alan Dal Pra
- Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 4, CH-3010 Bern, Switzerland
| | - Stéphane Supiot
- Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, Nantes-St-Herblain, 8 quai Moncousu, BP 70721, 44000 Nantes, France
| | - Padraig Warde
- Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada
| | - Robert G Bristow
- Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada
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Wilcox SW, Aherne NJ, McLachlan CS, McKay MJ, Last AJ, Shakespeare TP. Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: A comparison of Australian series. J Med Imaging Radiat Oncol 2015; 59:125-33. [DOI: 10.1111/1754-9485.12275] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Accepted: 11/20/2014] [Indexed: 11/28/2022]
Affiliation(s)
- Shea William Wilcox
- Radiation Oncology; North Coast Cancer Institute; Port Macquarie New South Wales Australia
| | - Noel J. Aherne
- Radiation Oncology; North Coast Cancer Institute; Coffs Harbour New South Wales Australia
| | - Craig Steven McLachlan
- Rural Clinical School; The University of New South Wales; Sydney New South Wales Australia
| | - Michael J. McKay
- Radiation Oncology; North Coast Cancer Institute; Lismore New South Wales Australia
| | - Andrew J. Last
- Radiation Oncology; North Coast Cancer Institute; Port Macquarie New South Wales Australia
| | - Thomas P. Shakespeare
- Radiation Oncology; North Coast Cancer Institute; Port Macquarie New South Wales Australia
- Radiation Oncology; North Coast Cancer Institute; Coffs Harbour New South Wales Australia
- Rural Clinical School; The University of New South Wales; Sydney New South Wales Australia
- Radiation Oncology; North Coast Cancer Institute; Lismore New South Wales Australia
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Doran MG, Watson PA, Cheal SM, Spratt DE, Wongvipat J, Steckler JM, Carrasquillo JA, Evans MJ, Lewis JS. Annotating STEAP1 regulation in prostate cancer with 89Zr immuno-PET. J Nucl Med 2014; 55:2045-9. [PMID: 25453051 DOI: 10.2967/jnumed.114.145185] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
UNLABELLED Antibodies and antibody-drug conjugates targeting the cell surface protein 6 transmembrane epithelial antigen of prostate 1 (STEAP1) are in early clinical development for the treatment of castration-resistant prostate cancer (PCa). In general, antigen expression directly affects the bioactivity of therapeutic antibodies, and the biologic regulation of STEAP1 is unusually complicated in PCa. Paradoxically, STEAP1 can be induced or repressed by the androgen receptor (AR) in different human PCa models, while also expressed in AR-null PCa. Consequently, there is an urgent need to translate diagnostic strategies to establish which regulatory mechanism predominates in patients to situate the appropriate therapy within standard of care therapies inhibiting AR. METHODS To this end, we prepared and evaluated (89)Zr-labeled MSTP2109A ((89)Zr-2109A), a radiotracer for PET derived from a fully humanized monoclonal antibody to STEAP1 in preclinical PCa models. RESULTS (89)Zr-2109A specifically localized to the STEAP1-positive human PCa models CWR22Pc, 22Rv1, and PC3. Moreover, (89)Zr-2109A sensitively measured treatment-induced changes (∼66% decline) in STEAP1 expression in CWR22PC in vitro and in vivo, a model we showed to express STEAP1 in an AR-dependent manner. CONCLUSION These findings highlight the ability of immuno-PET with (89)Zr-2109A to detect acute changes in STEAP1 expression and argue for an expansion of ongoing efforts to image PCa patients with (89)Zr-2109A to maximize the clinical benefit associated with antibodies or antibody-drug conjugates to STEAP1.
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Affiliation(s)
- Michael G Doran
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Philip A Watson
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sarah M Cheal
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniel E Spratt
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York; and
| | - John Wongvipat
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jeffrey M Steckler
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jorge A Carrasquillo
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Michael J Evans
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jason S Lewis
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York
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Strom TJ, Hutchinson SZ, Shrinath K, Cruz AA, Figura NB, Nethers K, Biagioli MC, Fernandez DC, Heysek RV, Wilder RB. External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer. Int Braz J Urol 2014; 40:474-83. [DOI: 10.1590/s1677-5538.ibju.2014.04.05] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Accepted: 03/05/2014] [Indexed: 11/21/2022] Open
Affiliation(s)
| | | | | | - Alex A. Cruz
- H. Lee Moffitt Cancer Center & Research Institute, USA
| | | | - Kevin Nethers
- H. Lee Moffitt Cancer Center & Research Institute, USA
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Tree AC, Khoo VS, van As NJ, Partridge M. Is biochemical relapse-free survival after profoundly hypofractionated radiotherapy consistent with current radiobiological models? Clin Oncol (R Coll Radiol) 2014; 26:216-29. [PMID: 24529742 DOI: 10.1016/j.clon.2014.01.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 12/19/2013] [Accepted: 01/02/2014] [Indexed: 11/25/2022]
Abstract
AIMS The α/β ratio for prostate cancer is thought to be low and less than for the rectum, which is usually the dose-limiting organ. Hypofractionated radiotherapy should therefore improve the therapeutic ratio, increasing cure rates with less toxicity. A number of models for predicting biochemical relapse-free survival have been developed from large series of patients treated with conventional and moderately hypofractionated radiotherapy. The purpose of this study was to test these models when significant numbers of patients treated with profoundly hypofractionated radiotherapy were included. MATERIALS AND METHODS A systematic review of the literature with regard to hypofractionated radiotherapy for prostate cancer was conducted, focussing on data recently presented on prostate stereotactic body radiotherapy. For the work described here, we have taken published biochemical control rates for a range of moderately and profoundly fractionated schedules and plotted these together with a range of radiobiological models, which are described. RESULTS The data reviewed show consistency between the various radiobiological model predictions and the currently observed data. CONCLUSION Current radiobiological models provide accurate predictions of biochemical relapse-free survival, even when profoundly hypofractionated patients are included in the analysis.
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Affiliation(s)
- A C Tree
- Royal Marsden NHS Foundation Trust, London, UK.
| | - V S Khoo
- Royal Marsden NHS Foundation Trust, London, UK; Institute of Cancer Research, London, UK
| | - N J van As
- Royal Marsden NHS Foundation Trust, London, UK
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Krishnan V, Delouya G, Bahary JP, Larrivée S, Taussky D. The Cancer of the Prostate Risk Assessment (CAPRA) score predicts biochemical recurrence in intermediate-risk prostate cancer treated with external beam radiotherapy (EBRT) dose escalation or low-dose rate (LDR) brachytherapy. BJU Int 2014; 114:865-71. [DOI: 10.1111/bju.12587] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Vimal Krishnan
- Departement of Radiation Oncology; Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame; Montreal Canada
| | - Guila Delouya
- Departement of Radiation Oncology; Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame; Montreal Canada
- CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal; Montreal Canada
| | - Jean-Paul Bahary
- Departement of Radiation Oncology; Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame; Montreal Canada
- CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal; Montreal Canada
| | - Sandra Larrivée
- CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal; Montreal Canada
| | - Daniel Taussky
- Departement of Radiation Oncology; Centre Hospitalier de l'Université de Montréal (CHUM), Hôpital Notre-Dame; Montreal Canada
- CRCHUM-Centre de Recherche du Centre Hospitalier de l'Université de Montréal; Montreal Canada
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Dearnaley DP, Jovic G, Syndikus I, Khoo V, Cowan RA, Graham JD, Aird EG, Bottomley D, Huddart RA, Jose CC, Matthews JHL, Millar JL, Murphy C, Russell JM, Scrase CD, Parmar MKB, Sydes MR. Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial. Lancet Oncol 2014; 15:464-73. [PMID: 24581940 DOI: 10.1016/s1470-2045(14)70040-3] [Citation(s) in RCA: 352] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
BACKGROUND The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer. Preliminary findings reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival. Based on the sample size calculation, we planned to analyse overall survival when 190 deaths occurred; this target has now been reached, after a median 10 years of follow-up. METHODS RT01 was a phase 3, open-label, international, randomised controlled trial enrolling men with histologically confirmed T1b-T3a, N0, M0 prostate cancer with prostate specific antigen of less than 50 ng/mL. Patients were randomly assigned centrally in a 1:1 ratio, using a computer-based minimisation algorithm stratifying by risk of seminal vesicle invasion and centre to either the control group (64 Gy in 32 fractions, the standard dose at the time the trial was designed) or the escalated-dose group (74 Gy in 37 fractions). Neither patients nor investigators were masked to assignment. All patients received neoadjuvant androgen deprivation therapy for 3-6 months before the start of conformal radiotherapy, which continued until the end of conformal radiotherapy. The coprimary outcome measures were biochemical progression-free survival and overall survival. All analyses were done on an intention-to-treat basis. Treatment-related side-effects have been reported previously. This trial is registered, number ISRCTN47772397. FINDINGS Between Jan 7, 1998, and Dec 20, 2001, 862 men were registered and 843 subsequently randomly assigned: 422 to the escalated-dose group and 421 to the control group. As of Aug 2, 2011, 236 deaths had occurred: 118 in each group. Median follow-up was 10·0 years (IQR 9·1-10·8). Overall survival at 10 years was 71% (95% CI 66-75) in each group (hazard ratio [HR] 0·99, 95% CI 0·77-1·28; p=0·96). Biochemical progression or progressive disease occurred in 391 patients (221 [57%] in the control group and 170 [43%] in the escalated-dose group). At 10 years, biochemical progression-free survival was 43% (95% CI 38-48) in the control group and 55% (50-61) in the escalated-dose group (HR 0·69, 95% CI 0·56-0·84; p=0·0003). INTERPRETATION At a median follow-up of 10 years, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-effects. FUNDING UK Medical Research Council.
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Affiliation(s)
- David P Dearnaley
- The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London and Sutton, UK
| | - Gordana Jovic
- Medical Research Council Clinical Trials Unit at University College London, London, UK
| | | | - Vincent Khoo
- The Royal Marsden NHS Foundation Trust, London and Sutton, UK
| | | | | | | | | | - Robert A Huddart
- The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, London and Sutton, UK
| | | | | | | | - Claire Murphy
- Medical Research Council Clinical Trials Unit at University College London, London, UK
| | | | | | - Mahesh K B Parmar
- Medical Research Council Clinical Trials Unit at University College London, London, UK
| | - Matthew R Sydes
- Medical Research Council Clinical Trials Unit at University College London, London, UK.
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A New Risk Classification System for Therapeutic Decision Making with Intermediate-risk Prostate Cancer Patients Undergoing Dose-escalated External-beam Radiation Therapy. Eur Urol 2013; 64:895-902. [DOI: 10.1016/j.eururo.2013.03.033] [Citation(s) in RCA: 289] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2013] [Accepted: 03/08/2013] [Indexed: 12/22/2022]
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Boissier R, Karsenty G, Muracciole X, Daniel L, Delaporte V, Maurin C, Coulange C, Lechevallier E. [Comparative study of radical prostatectomy versus external beam radiotherapy (75.6 Gy) combined with hormone therapy for prostate cancer of intermediate D'Amico risk classification]. Prog Urol 2013; 23:861-8. [PMID: 24034798 DOI: 10.1016/j.purol.2013.04.007] [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: 02/25/2013] [Revised: 04/02/2013] [Accepted: 04/07/2013] [Indexed: 10/26/2022]
Abstract
INTRODUCTION Thirty-three percent of the localized cancers belongs initially to the group of intermediate risk of D'Amico. The standard treatments validated by the French Association of Urology are the radical prostatectomy and the external beam radiotherapy. OBJECTIVES We retrospectively compared the carcinologic results of the radical prostatectomy±adjuvant treatment (RP) and the external beam radiotherapy combining high dose (75.6 Gy) and short hormonotherapy (RH), in the treatment of intermediate risk prostate cancer. The series consisted of 143 patients treated between 2000 and 2006 in the department of Urology and Kidney transplantation of the Conception Hospital, Marseilles. The main assessment criteria was the survival without biological recurrence (SBR). RESULTS The median follow-up was 90 months [59-51]. The 5 years and 8 years SBR were 85% and 73% in the RH group, versus 74% and 65% with RP (P=0.196). There was a significant difference between the series: on the age of diagnosis (63.9 versus 73.3 years, P<0.001), the Charlson score of comorbidity (2 versus 3, P<0.001) and the number of intermediate criteria per patients (one intermediate criteria: RP 74% versus 57%, P<0.01). CONCLUSION According to our study, there was no superiority of the radical prostatectomy±adjuvant treatment or the external radiotherapy combining high dose and concomitant short hormonotherapy on the survival without biological recurrence at 5 and 8 years. Many studies confirm that a concomitant hormonotherapy increases the carcinologic control, even with a high rate external beam radiotherapy.
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Affiliation(s)
- R Boissier
- Service d'urologie et transplantation rénale, Aix-Marseille université, hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France.
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Ragnum HB, Røe K, Holm R, Vlatkovic L, Nesland JM, Aarnes EK, Ree AH, Flatmark K, Seierstad T, Lilleby W, Lyng H. Hypoxia-independent downregulation of hypoxia-inducible factor 1 targets by androgen deprivation therapy in prostate cancer. Int J Radiat Oncol Biol Phys 2013; 87:753-60. [PMID: 24035332 DOI: 10.1016/j.ijrobp.2013.07.023] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Revised: 07/02/2013] [Accepted: 07/17/2013] [Indexed: 11/29/2022]
Abstract
PURPOSE We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred. METHODS AND MATERIALS Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvant ADT was assessed by immunohistochemistry. RESULTS A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001). CONCLUSIONS AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to tumor regression. HIF1α expression is probably not a useful hypoxia biomarker during ADT in prostate cancer.
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Affiliation(s)
- Harald Bull Ragnum
- Department of Radiation Biology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
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Point: There is a need for supplemental XRT with brachytherapy in the treatment of intermediate-risk prostate cancer patients. Brachytherapy 2013; 12:389-92. [PMID: 23988506 DOI: 10.1016/j.brachy.2013.07.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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