# Systemic Therapy for Metastatic Hormone-Sensitive Prostate Cancer: A Randomized Controlled Trial-Based Network Meta-Analysis

## TL;DR

This study compares different treatment strategies for metastatic hormone-sensitive prostate cancer using a network meta-analysis of clinical trials to determine the most effective options.

## Contribution

The study provides new insights into optimal treatment combinations for metastatic hormone-sensitive prostate cancer using network meta-analysis of randomized trials.

## Key findings

- ADT + apalutamide showed the highest probability of improving overall and failure-free survival.
- Abiraterone, enzalutamide, and apalutamide were most effective across subgroups, with apalutamide showing the strongest effects.
- Treatment rankings varied by patient subgroup, highlighting the importance of individualized treatment approaches.

## Abstract

To compare the effects of different treatment strategies for metastatic hormone-sensitive prostate cancer (mHSPC) using a network meta-analysis.

English databases (PubMed, Embase, and medRxiv) and Chinese databases (Wanfang and CNKI) were searched for randomized controlled trials (RCTs) on the treatment of mHSPC from inception to June 1, 2021. The overall survival (OS) and failure-free survival (FFS) reported by the included studies were extracted from each study for network meta-analysis. Moreover, the priority ranks of the treatment methods were determined.

A total of 18 RCTs with 14,682 patients were included in this study. Androgen-deprivation therapy (ADT) + apalutamide (APA) showed the highest probability of improving the OS (96.2%) and FFS (68.0%). In addition, the patients were stratified into ten subgroups as follows: low/high tumor burden (CHAARTED criteria); Gleason score ≤7/≥8; Eastern Cooperative Oncology Group (ECOG) = 0/≥1; with/without prechemotherapy; and cooperative with/without concomitant radiotherapy. For the improvement of OS, the leading treatments were as follows: (1) ADT + enzalutamide (ENZA) (64.1%)/ADT + abiraterone acetate + prednisone (AAP) (54.3%); (2) ADT + ENZA (41.9%)/ADT + APA (39.2%); (3) ADT + ENZA (39.2%)/ADT + APA (32.1%); (4) ADT + radiotherapy (51%)/ADT + ENZA (76.7%); (5) ADT + AAP (51%)/ADT + AAP (60%).

Three endocrine therapy drugs, abiraterone, enzalutamide, and APA, exhibited the best effects in improving the OS and FFS in all patients and subgroups; however, APA had the most prominent treatment effects. Therefore, ADT + APA should be applied as the common treatment for patients with HSPC based on objective and clinical conditions. Trial Registration. This meta-analysis has been registered on the PROSPERO website (Trial number: https://www.crd.york.ac.uk/prospero/CRD42020221062).