PURPOSE: There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa. METHODS: MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS). RESULTS: The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups. CONCLUSION: The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.
PURPOSE: There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa. METHODS: MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS). RESULTS: The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups. CONCLUSION: The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.
Authors: Mack Roach; Jennifer Moughan; Colleen A F Lawton; Adam P Dicker; Kenneth L Zeitzer; Elizabeth M Gore; Young Kwok; Michael J Seider; I-Chow Hsu; Alan C Hartford; Eric M Horwitz; Kosj Yamoah; Christopher U Jones; Jeff M Michalski; W Robert Lee; Thomas M Pisansky; Rachel Rabinovitch; Marvin Rotman; Rodger M Pryzant; Harold E Kim; Charles R Thomas; William U Shipley; Howard M Sandler Journal: Lancet Oncol Date: 2018-10-10 Impact factor: 41.316
Authors: Anthony V D'Amico; Ming-Hui Chen; Juanita Crook; John G Armstrong; Shawn Malone; Allison Steigler; Mary Dunne; Philip W Kantoff; James W Denham Journal: J Clin Oncol Date: 2011-10-31 Impact factor: 44.544
Authors: Colleen A F Lawton; Xiaolei Lin; Gerald E Hanks; Herbert Lepor; David J Grignon; Harmar D Brereton; Meena Bedi; Seth A Rosenthal; Kenneth L Zeitzer; Varagur M Venkatesan; Eric M Horwitz; Thomas M Pisansky; Harold Kim; Matthew B Parliament; Rachel Rabinovitch; Mack Roach; Young Kwok; James J Dignam; Howard M Sandler Journal: Int J Radiat Oncol Biol Phys Date: 2017-02-12 Impact factor: 7.038
Authors: Almudena Zapatero; Araceli Guerrero; Xavier Maldonado; Ana Alvarez; Carmen Gonzalez San Segundo; Maria Angeles Cabeza Rodríguez; Victor Macias; Agustí Pedro Olive; Francesc Casas; Ana Boladeras; Carmen Martín de Vidales; Maria Luisa Vazquez de la Torre; Salvador Villà; Aitor Perez de la Haza; Felipe A Calvo Journal: Lancet Oncol Date: 2015-02-19 Impact factor: 41.316
Authors: Michel Bolla; Theodorus M de Reijke; Geertjan Van Tienhoven; Alphonsus C M Van den Bergh; Jorg Oddens; Philip M P Poortmans; Eliahu Gez; Paul Kil; Atif Akdas; Guy Soete; Oleg Kariakine; Elsbietha M van der Steen-Banasik; Elena Musat; Marianne Piérart; Murielle E Mauer; Laurence Collette Journal: N Engl J Med Date: 2009-06-11 Impact factor: 91.245
Authors: Jacques Laverdière; Abdenour Nabid; Luis Diaz De Bedoya; Annie Ebacher; Andre Fortin; Chang Shu Wang; François Harel Journal: J Urol Date: 2004-03 Impact factor: 7.450
Authors: Daniel E Spratt; Michael J Evans; Brian J Davis; Michael G Doran; Man Xia Lee; Neel Shah; John Wongvipat; Kathryn E Carnazza; George G Klee; William Polkinghorn; Donald J Tindall; Jason S Lewis; Charles L Sawyers Journal: Cancer Res Date: 2015-10-02 Impact factor: 12.701
Authors: Neal S McCall; Yuan Liu; Sagar A Patel; Bruce Hershatter; Drew Moghanaki; Karen D Godette; Sheela Hanasoge; Pretesh Patel; Benjamin W Fischer-Valuck; Joseph W Shelton; Ashesh B Jani Journal: Adv Radiat Oncol Date: 2021-09-10
Authors: Xiangyi Li; GuemHee Baek; Suzanne Carreira; Wei Yuan; Shihong Ma; Mia Hofstad; Sora Lee; Yunpeng Gao; Claudia Bertan; Maria de Los Dolores Fenor de la Maza; Prasanna G Alluri; Sandeep Burma; Benjamin Pc Chen; Ganesh V Raj; Johann de Bono; Yves Pommier; Ram S Mani Journal: JCI Insight Date: 2022-05-09
Authors: Pedro C Lara; Juan I Rodríguez-Melcón; Amalia Palacios-Eito; Antonio Lozano; Asunción Hervás-Morón; Elena Villafranca; Alfonso Gómez-Iturriaga; Gemma Sancho; Xavier Maldonado Journal: Front Oncol Date: 2022-07-14 Impact factor: 5.738
Authors: Oliver Schumacher; Daniel A Galvão; Dennis R Taaffe; Nigel Spry; Dickon Hayne; Colin Tang; Raphael Chee; Robert U Newton Journal: JCO Oncol Pract Date: 2022-05-18
Authors: Lauren K Jillson; Gabriel A Yette; Teemu D Laajala; Wayne D Tilley; James C Costello; Scott D Cramer Journal: Cancers (Basel) Date: 2021-06-30 Impact factor: 6.639