Overall Survival After Systemic Treatment in High-volume Versus Low-volume Metastatic Hormone-sensitive Prostate Cancer: Systematic Review and Network Meta-analysis

TY - JOUR

T1 - Overall Survival After Systemic Treatment in High-volume Versus Low-volume Metastatic Hormone-sensitive Prostate Cancer: Systematic Review and Network Meta-analysis

AU - Wenzel, Mike

AU - Würnschimmel, Christoph

AU - Nocera, Luigi

AU - Collà Ruvolo, Claudia

AU - Tian, Zhe

AU - Shariat, Shahrokh F

AU - Saad, Fred

AU - Briganti, Alberto

AU - Tilki, Derya

AU - Graefen, Markus

AU - Kluth, Luis A

AU - Roos, Frederik C

AU - Mandel, Philipp

AU - Chun, Felix K H

AU - Karakiewicz, Pierre I

N1 - Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2022/3

Y1 - 2022/3

N2 - CONTEXT: Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes.OBJECTIVE: To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs).EVIDENCE ACQUISITION: First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification.EVIDENCE SYNTHESIS: The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone.CONCLUSIONS: In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint.PATIENT SUMMARY: We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.

AB - CONTEXT: Novel prospective randomized controlled observations addressing combination therapy in metastatic hormone-sensitive prostate cancer (mHSPC) have demonstrated promising overall survival (OS) outcomes.OBJECTIVE: To compare these novel findings and systematically review and address them within formal network meta-analyses (NMAs) that include observations from other prospective randomized controlled trials (RCTs).EVIDENCE ACQUISITION: First, we focused on abiraterone, enzalutamide, apalutamide, and docetaxel effects on OS in mHSPC using the PRISMA methodology. PubMed and abstracts identified prospective RCTs in first-line mHSPC. Second, we focused on mature studies that reached median OS and tested OS between abiraterone and docetaxel with tumor burden stratification.EVIDENCE SYNTHESIS: The first part included seven studies (n = 6639) and the second part, five studies (n = 4462). In the first part, abiraterone ranked first for high-volume mHSPC. Conversely, enzalutamide ranked first for low-volume mHSPC. In the second part, abiraterone treatment in high-volume mHSPC resulted in median OS of 50.1 mo and exceeded that with docetaxel (45.9 mo) and ADT alone (34.0 mo). Docetaxel treatment in low volume mHSPC resulted in median OS of 69.5 mo versus 67.7 mo with ADT alone.CONCLUSIONS: In conventional NMA that relied on conventional hazard ratios, differences were identified with respect to the relative efficacy of the combination therapies examined; abiraterone dominated the alternatives in high-volume mHSPC. In part two, which relied on trials for which median OS is available, comparison of abiraterone versus docetaxel revealed a 4-mo difference in OS in high-volume mHSPC. Conventional NMA may have overestimated the importance of treatment efficacy instead of focusing on median OS duration, which might represent a more important clinical endpoint.PATIENT SUMMARY: We reviewed studies on hormonal treatments and chemotherapy used for prostate cancer that has spread outside the prostate gland (metastatic prostate cancer, mPC). We found that the best overall survival was with the hormone agents abiraterone in high-volume mPC and enzalutamide in low-volume mPC. In comparison to the chemotherapy drug docetaxel, median overall survival with abiraterone was 4 months longer among patients with mPC.

U2 - 10.1016/j.euf.2021.04.003

DO - 10.1016/j.euf.2021.04.003

M3 - SCORING: Review article

C2 - 33853754

VL - 8

SP - 399

EP - 408

JO - EUR UROL FOCUS

JF - EUR UROL FOCUS

SN - 2405-4569

IS - 2

ER -