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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

Autores: Kishan, A. U. (Autor de correspondencia); Steigler, A.; Denham, J. W.; Zapatero, A.; Guerrero, A.; Joseph, D.; Maldonado, X.; Wong, J. K.; Stish, B. J.; Dess, R. T.; Pilar, A.; Reddy, C.; Wedde, T. B.; Lilleby, W. A.; Fiano, R.; Merrick, G. S.; Stock, R. G.; Demanes, D. J.; Moran, B. J.; Tran, P. T.; Martín Pastor, Santiago Mariano; Martínez Monge, Rafael; Krauss, D. J.; Abu-Isa, E. I.; Pisansky, T. M.; Choo, C. R.; Song, D. Y.; Greco, S.; Deville, C.; McNutt, T.; DeWeese, T. L.; Ross, A. E.; Ciezki, J. P.; Tilki, D.; Karnes, R. J.; Tosoian, J. J.; Nickols, N. G.; Bhat, P.; Shabsovich, D.; Juarez, J. E.; Jiang, T.; Ma, T. M.; Xiang, M.; Philipson, R.; Chang, A.; Kupelian, P. A.; Rettig, M. B.; Feng, F. Y.; Berlin, A.; Tward, J. D.
Título de la revista: JAMA ONCOLOGY
ISSN: 2374-2437
Volumen: 8
Número: 3
Páginas: e216871
Fecha de publicación: 2022
Y 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 Deprivacion Androgenica y Radio Terapia (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 outcomewas DMFS; secondary outcomewas 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.