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
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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. / Kishan, Amar U; Steigler, Alison; Denham, James W; Zapatero, Almudena; Guerrero, Araceli; Joseph, David; Maldonado, Xavier; Wong, Jessica K; Stish, Bradley J; Dess, Robert T; 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; Martin, Santiago; Martinez-Monge, Rafael; Krauss, Daniel J; Abu-Isa, Eyad I; Pisansky, Thomas M; Choo, C Richard; Song, Daniel Y; Greco, Stephen; Deville, Curtiland; McNutt, Todd; DeWeese, Theodore L; Ross, Ashley E; Ciezki, Jay P; Tilki, Derya; Karnes, R Jeffrey; Tosoian, Jeffrey J; Nickols, Nicholas G; Bhat, Prashant; Shabsovich, David; Juarez, Jesus E; Jiang, Tommy; Ma, T Martin; Xiang, Michael; Philipson, Rebecca; Chang, Albert; Kupelian, Patrick A; Rettig, Matthew B; Feng, Felix Y; Berlin, Alejandro; Tward, Jonathan D; Davis, Brian J; Reiter, Robert E; Steinberg, Michael L; Elashoff, David; Boutros, Paul C; Horwitz, Eric M; Tendulkar, Rahul D; Spratt, Daniel E; Romero, Tahmineh.
In: JAMA ONCOL, Vol. 8, No. 3, 01.03.2022, p. e216871.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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
T2 - A Patient-Level Data Analysis of 3 Cohorts
AU - Kishan, Amar U
AU - Steigler, Alison
AU - Denham, James W
AU - Zapatero, Almudena
AU - Guerrero, Araceli
AU - Joseph, David
AU - Maldonado, Xavier
AU - Wong, Jessica K
AU - Stish, Bradley J
AU - Dess, Robert T
AU - Pilar, Avinash
AU - Reddy, Chandana
AU - Wedde, Trude B
AU - Lilleby, Wolfgang A
AU - Fiano, Ryan
AU - Merrick, Gregory S
AU - Stock, Richard G
AU - Demanes, D Jeffrey
AU - Moran, Brian J
AU - Tran, Phuoc T
AU - Martin, Santiago
AU - Martinez-Monge, Rafael
AU - Krauss, Daniel J
AU - Abu-Isa, Eyad I
AU - Pisansky, Thomas M
AU - Choo, C Richard
AU - Song, Daniel Y
AU - Greco, Stephen
AU - Deville, Curtiland
AU - McNutt, Todd
AU - DeWeese, Theodore L
AU - Ross, Ashley E
AU - Ciezki, Jay P
AU - Tilki, Derya
AU - Karnes, R Jeffrey
AU - Tosoian, Jeffrey J
AU - Nickols, Nicholas G
AU - Bhat, Prashant
AU - Shabsovich, David
AU - Juarez, Jesus E
AU - Jiang, Tommy
AU - Ma, T Martin
AU - Xiang, Michael
AU - Philipson, Rebecca
AU - Chang, Albert
AU - Kupelian, Patrick A
AU - Rettig, Matthew B
AU - Feng, Felix Y
AU - Berlin, Alejandro
AU - Tward, Jonathan D
AU - Davis, Brian J
AU - Reiter, Robert E
AU - Steinberg, Michael L
AU - Elashoff, David
AU - Boutros, Paul C
AU - Horwitz, Eric M
AU - Tendulkar, Rahul D
AU - Spratt, Daniel E
AU - Romero, Tahmineh
PY - 2022/3/1
Y1 - 2022/3/1
N2 - 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.
AB - 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.
KW - Androgen Antagonists/adverse effects
KW - Androgens
KW - Brachytherapy/adverse effects
KW - Data Analysis
KW - Humans
KW - Male
KW - Middle Aged
KW - Prostatic Neoplasms/drug therapy
KW - Retrospective Studies
U2 - 10.1001/jamaoncol.2021.6871
DO - 10.1001/jamaoncol.2021.6871
M3 - SCORING: Journal article
C2 - 35050303
VL - 8
SP - e216871
JO - JAMA ONCOL
JF - JAMA ONCOL
SN - 2374-2437
IS - 3
ER -