@article{975c72660b8d4e53853e7c72e17e6ecc,
title = "Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer A Patient-Level Data Analysis of 3 Cohorts",
abstract = "IMPORTANCE Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. OBJECTIVE To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTINGS, AND PARTICIPANTS This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivaci{\'o}n Androg{\'e}nica y Radio Terap{\'i}a (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. EXPOSURES High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). MAIN OUTCOMES AND MEASURES The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). RESULTS This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P =.01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P =.01). CONCLUSIONS AND RELEVANCE These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.",
author = "Kishan, {Amar U.} and Alison Steigler and Denham, {James W.} and Almudena Zapatero and Araceli Guerrero and David Joseph and Xavier Maldonado and Wong, {Jessica K.} and Stish, {Bradley J.} and Dess, {Robert T.} and Avinash Pilar and Chandana Reddy and Wedde, {Trude B.} and Lilleby, {Wolfgang A.} and Ryan Fiano and Merrick, {Gregory S.} and Stock, {Richard G.} and Demanes, {D. Jeffrey} and Moran, {Brian J.} and Tran, {Phuoc T.} and Santiago Martin and Rafael Martinez-Monge and Krauss, {Daniel J.} and Abu-Isa, {Eyad I.} and Pisansky, {Thomas M.} and Choo, {C. Richard} and Song, {Daniel Y.} and Stephen Greco and Curtiland Deville and Todd McNutt and DeWeese, {Theodore L.} and Ross, {Ashley E.} and Ciezki, {Jay P.} and Derya Tilki and Karnes, {R. Jeffrey} and Tosoian, {Jeffrey J.} and Nickols, {Nicholas G.} and Prashant Bhat and David Shabsovich and Juarez, {Jesus E.} and Tommy Jiang and Ma, {T. Martin} and Michael Xiang and Rebecca Philipson and Albert Chang and Kupelian, {Patrick A.} and Rettig, {Matthew B.} and Feng, {Felix Y.} and Alejandro Berlin and Tward, {Jonathan D.} and Davis, {Brian J.} and Reiter, {Robert E.} and Steinberg, {Michael L.} and David Elashoff and Boutros, {Paul C.} and Horwitz, {Eric M.} and Tendulkar, {Rahul D.} and Spratt, {Daniel E.} and Tahmineh Romero",
note = "Funding Information: Funding/Support: This study was supported by grants from the US National Institutes of Health Specialized Programs of Research Excellence in Prostate Cancer (No. P50CA09213, Dr Kishan; P50CA186786, Dr Spratt), the Radiological Society of North America (No. RSD1836, Dr Kishan), the STOP Cancer Organization (No. RSD1836, Dr Kishan), and the US Department of Defense (No. PC151068, Dr Spratt) and was supported by the Prostate Cancer Foundation (Drs Kishan, Spratt, Nickols), the Jonsson Comprehensive Cancer Center (Dr Kishan), the Bershad Family Trust (Dr Kishan), and the DeSilva Family Trust (Dr Kishan). Funding Information: reported consulting fees and speaking honoraria from Varian Medical Systems, ViewRay, and Intelligent Automation; equity in ViewRay; and serving on the Janssen advisory board, all outside the submitted work. Dr Zapatero reported consulting and/or speaking fees from Astellas Pharma, Bayer, and Janssen; serving on the Bayer advisory board; and grants from SEOR/GICOR, all outside the submitted work. Dr Joseph reported grants from NHMRC (Australia) during the conduct of the study. Dr Tran reported grants from Astellas and Bayer and personal fees from RefleXion, Johnson & Johnson, and Myovant during the conduct of the study; and holding a patent for Compounds and Methods of Use in Ablative Radiotherapy (No. 9114158) with royalties paid from Natsar Pharm. Dr Song reported grants from BioProtect, Candel Therapeutics, Bayer, Celgene, and the US National Cancer Institute, all outside the submitted work. Dr Ross reported personal fees Funding Information: from Bayer, Astellas, Blue Earth, Myovant, GenomeDx Biosciences, and Janssen outside the submitted work. Dr Tilki reported personal fees from Ipsen, Exact Sciences, miR Scientific, AstraZeneca, Apogepha, Roche, Takeda, and AAA (Novartis) outside the submitted work. Dr Tosoian reported equity in LynxDx outside the submitted work. Dr Nickols reported grants from Lantheus, Janssen, and Bayer, and personal fees from OncoLinea, all outside the submitted work. Dr Rettig reported consulting fees from Ambrx, Amgen, Roivant Sciences, Clovis, Bayer, and Janssen; nonfinancial support from Merck; and grants from Novartis, all outside the submitted work; and holding a pending patent for Inhibitors of the N-terminus of the Androgen Receptor. Dr Feng reported consulting fees from Janssen, Blue Earth Diagnostics, Astellas, Myovant, Roivant Sciences, Bayer, Bristol Myers Squibb; stock options in Serimmune and BlueStar Genomics; serving on the advisory boards of Serimmune and BlueStar Genomics; consulting fees from Exact Sciences and Varian; and equity in Artera, all outside the submitted work. Dr Tward reported grants from Bayer and serving on the advisory boards of Myriad, Blue Earth, Boston Scientific, and Merck, all outside the submitted work. Dr Steinberg reported honoraria from ViewRay. Dr Boutros reported holding patents on biomarkers for localized prostate cancer and serving on the advisory boards to Sage BioNetworks, BioSymetrics, and Intersect Diagnostics. Dr Spratt reported grants from Janssen and personal fees from AstraZeneca, Varian, and Boston Scientific, outside the submitted work. No other disclosures were reported. Publisher Copyright: {\textcopyright} 2022 American Medical Association",
year = "2022",
doi = "10.1001/jamaoncol.2021.6871",
language = "English",
volume = "8",
journal = "JAMA Oncology",
issn = "2374-2437",
publisher = "American Medical Association",
number = "3",
}
