External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis

TY - JOUR

T1 - External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis

AU - Patel, Sagar A

AU - Ma, Ting Martin

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 - 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 - DeWeese, Theodore L

AU - Tilki, Derya

AU - Ciezki, Jay P

AU - Karnes, R Jeffrey

AU - Nickols, Nicholas G

AU - Rettig, Matthew B

AU - Feng, Felix Y

AU - Berlin, Alejandro

AU - Tward, Jonathan D

AU - Davis, Brian J

AU - Reiter, Robert E

AU - Boutros, Paul C

AU - Romero, Tahmineh

AU - Horwitz, Eric M

AU - Tendulkar, Rahul D

AU - Steinberg, Michael L

AU - Spratt, Daniel E

AU - Xiang, Michael

AU - Kishan, Amar U

N1 - Copyright © 2022 Elsevier Inc. All rights reserved.

PY - 2023/3/1

Y1 - 2023/3/1

N2 - PURPOSE: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear.METHODS AND MATERIALS: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression.RESULTS: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38).CONCLUSIONS: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

AB - PURPOSE: Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear.METHODS AND MATERIALS: This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression.RESULTS: Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38).CONCLUSIONS: In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

KW - Male

KW - Humans

KW - Brachytherapy/methods

KW - Prostatic Neoplasms/drug therapy

KW - Cohort Studies

KW - Androgen Antagonists/therapeutic use

KW - Neoplasm Grading

KW - Retrospective Studies

U2 - 10.1016/j.ijrobp.2022.09.075

DO - 10.1016/j.ijrobp.2022.09.075

M3 - SCORING: Journal article

C2 - 36179990

VL - 115

SP - 645

EP - 653

JO - INT J RADIAT ONCOL

JF - INT J RADIAT ONCOL

SN - 0360-3016

IS - 3

ER -