- 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
- Creator
- Kishan, Amar U.; Steigler, Alison; Pilar, Avinash; Reddy, Chandana; Wedde, Trude B.; Lilleby, Wolfgang A.; Fiano, Ryan; Merrick, Gregory S.; Stock, Richard G.; Demanes, D. Jeffrey; Moran, Brian J.; Tran, Phuoc T.; Denham, James W.; Martin, S; Martinez-Monge, R; Krauss, DJ; Abu-Isa, EI; Pisansky, TM; Choo, CR; Song, DY; Greco, S; Deville, C; McNutt, T; Zapatero, Almudena; DeWeese, TL; Ross, AE; Ciezki, JP; Tilki, D; Karnes, RJ; Tosoian, JJ; Nickols, NG; Bhat, P; Shabsovich, D; Juarez, JE; Guerrero, Araceli; Jiang, T; Ma, TM; Xiang, M; Philipson, R; Chang, A; Kupelian, PA; Rettig, MB; Feng, FY; Berlin, A; Tward, JD; Joseph, David; Davis, BJ; Reiter, RE; Steinberg, ML; Elashoff, D; Boutros, PC; Horwitz, EM; Tendulkar, RD; Spratt, DE; Romero, T; Maldonado, Xavier; Wong, Jessica K.; Stish, Bradley J.; Dess, Robert T.
- Relation
- JAMA Oncology Vol. 8, Issue 3, no. e216871
- Publisher Link
- http://dx.doi.org/10.1001/jamaoncol.2021.6871
- Publisher
- American Medical Association
- Resource Type
- journal article
- Date
- 2022
- Description
- 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 Deprivación Androgénica y Radio Terapía (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.
- Subject
- androgen deprivation therapy (ADT); prostate cancer; radiotherapy; brachytherapy; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1464742
- Identifier
- uon:47094
- Identifier
- ISSN:2374-2437
- Language
- eng
- Reviewed
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