Lorenzo Tosco1, Alberto Briganti2, Antony Vincent D'amico3, James Eastham4, Mario Eisenberger5, Martin Gleave6, Karin Haustermans7, Christopher J Logothetis8, Fred Saad9, Christopher Sweeney10, Mary-Ellen Taplin10, Karim Fizazi11. 1. Department of Urology, University Hospitals Leuven, Leuven, Belgium; Nuclear Medicine & Molecular Imaging, KU Leuven, Leuven, Belgium. Electronic address: lorenzo.tosco@uzleuven.be. 2. Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. 3. Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA, USA. 4. Urology Service at the Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 5. Department of Oncology in the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 6. The Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. 7. Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium. 8. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 9. Department of Urology, Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, Quebec, Canada. 10. Dana-Farber Cancer Institute, Boston, MA, USA. 11. Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
Abstract
CONTEXT: Systemic therapies, combined with local treatment for high-risk prostate cancer, are recommended by the international guidelines for specific subgroups of patients; however, for many of the clinical scenarios, it remains a research field. OBJECTIVE: To perform a systematic review, and describe current evidence and perspectives about the multimodal treatment of high-risk prostate cancer. EVIDENCE ACQUISITION: We performed a systematic review of PubMED, Embase, Cochrane Library, European Society of Medical Oncology/American Society of Clinical Oncology Annual proceedings, and clinicalTrial.gov between January 2010 and February 2018 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. EVIDENCE SYNTHESIS: Seventy-seven prospective trials were identified. According to multiple randomized trials, combining androgen deprivation therapy (ADT) with external-beam radiotherapy (EBRT) outperforms EBRT alone for both relapse-free and overall survival. Neoadjuvant ADT did not show significant improvement compared with prostatectomy alone. The role of adjuvant ADT after prostatectomy in patients with high-risk disease is still debated, with lack of data from phase 3 trials in pN0 patients. Novel androgen pathway inhibitors have been tested only in early-phase trials in addition to primary treatment. GETUG 12, RTOG 0521, and nonmetastatic subgroup of the STAMPEDE trial showed improved relapse-free survival for docetaxel in patients treated with EBRT plus ADT, although mature metastasis-free survival data are still pending. Both the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free survival for adjuvant docetaxel after prostatectomy. CONCLUSIONS: In contrast to the clearly demonstrated survival benefits of long-term adjuvant ADT when used with EBRT, its role after prostatectomy remains unclear especially in pN0 patients. Adding docetaxel to EBRT-ADT improves relapse-free survival, with immature results on overall survival. Novel androgen receptor pathway inhibitors are currently being tested in the neoadjuvant and adjuvant setting. PATIENT SUMMARY: Treatment of high-risk prostate cancer is based on a multimodality approach that includes systemic treatments. The best treatment or therapy combination remains to be defined.
CONTEXT: Systemic therapies, combined with local treatment for high-risk prostate cancer, are recommended by the international guidelines for specific subgroups of patients; however, for many of the clinical scenarios, it remains a research field. OBJECTIVE: To perform a systematic review, and describe current evidence and perspectives about the multimodal treatment of high-risk prostate cancer. EVIDENCE ACQUISITION: We performed a systematic review of PubMED, Embase, Cochrane Library, European Society of Medical Oncology/American Society of Clinical Oncology Annual proceedings, and clinicalTrial.gov between January 2010 and February 2018 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. EVIDENCE SYNTHESIS: Seventy-seven prospective trials were identified. According to multiple randomized trials, combining androgen deprivation therapy (ADT) with external-beam radiotherapy (EBRT) outperforms EBRT alone for both relapse-free and overall survival. Neoadjuvant ADT did not show significant improvement compared with prostatectomy alone. The role of adjuvant ADT after prostatectomy in patients with high-risk disease is still debated, with lack of data from phase 3 trials in pN0 patients. Novel androgen pathway inhibitors have been tested only in early-phase trials in addition to primary treatment. GETUG 12, RTOG 0521, and nonmetastatic subgroup of the STAMPEDE trial showed improved relapse-free survival for docetaxel in patients treated with EBRT plus ADT, although mature metastasis-free survival data are still pending. Both the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free survival for adjuvant docetaxel after prostatectomy. CONCLUSIONS: In contrast to the clearly demonstrated survival benefits of long-term adjuvant ADT when used with EBRT, its role after prostatectomy remains unclear especially in pN0 patients. Adding docetaxel to EBRT-ADT improves relapse-free survival, with immature results on overall survival. Novel androgen receptor pathway inhibitors are currently being tested in the neoadjuvant and adjuvant setting. PATIENT SUMMARY: Treatment of high-risk prostate cancer is based on a multimodality approach that includes systemic treatments. The best treatment or therapy combination remains to be defined.
Authors: Weranja Ranasinghe; Daniel D Shapiro; Miao Zhang; Tharakeswara Bathala; Nora Navone; Timothy C Thompson; Bradley Broom; Ana Aparicio; Shi-Ming Tu; Chad Tang; John W Davis; Louis Pisters; Brian F Chapin Journal: Nat Rev Urol Date: 2021-04-06 Impact factor: 14.432
Authors: Robert T Dess; Krithika Suresh; Michael J Zelefsky; Stephen J Freedland; Brandon A Mahal; Matthew R Cooperberg; Brian J Davis; Eric M Horwitz; Martha K Terris; Christopher L Amling; William J Aronson; Christopher J Kane; William C Jackson; Jason W D Hearn; Curtiland Deville; Theodore L DeWeese; Stephen Greco; Todd R McNutt; Daniel Y Song; Yilun Sun; Rohit Mehra; Samuel D Kaffenberger; Todd M Morgan; Paul L Nguyen; Felix Y Feng; Vidit Sharma; Phuoc T Tran; Bradley J Stish; Thomas M Pisansky; Nicholas G Zaorsky; Fabio Ynoe Moraes; Alejandro Berlin; Antonio Finelli; Nicola Fossati; Giorgio Gandaglia; Alberto Briganti; Peter R Carroll; R Jeffrey Karnes; Michael W Kattan; Matthew J Schipper; Daniel E Spratt Journal: JAMA Oncol Date: 2020-12-01 Impact factor: 31.777