# Best therapeutic approach in metastatic hormone-sensitive prostate cancer based on disease volume: a systematic review and network meta-analysis

## TL;DR

This study compares treatments for prostate cancer based on disease spread and timing of metastasis to guide optimal therapy choices.

## Contribution

The study provides evidence-based treatment recommendations for metastatic hormone-sensitive prostate cancer stratified by disease volume and metastasis timing.

## Key findings

- Triplet therapy improves survival in high-volume/synchronous prostate cancer.
- ARPI/ADT doublets are most effective for low-volume disease.
- Triplets and doublets show similar effectiveness in high-volume/metachronous cases.

## Abstract

With new treatment strategies approved in metastatic hormone-sensitive prostate cancer (mHSPC), heterogeneity across trials hinders the physicians’ choice for first-line treatment.

We conducted a systematic review and network meta-analysis to assess the efficacy of currently approved treatments for mHSPC stratifying patients according to their disease burden (high- vs. low-volume as per CHAARTED criteria) and onset of metastatic disease (synchronous vs. metachronous).

Eleven randomized controlled trials (RCTs) published until October 30, 2024 were included. Treatment regimens were grouped as triplets for combinations of docetaxel, androgen receptor pathway inhibitors (ARPIs) and androgen-deprivation therapy (ADT), separate doublets for docetaxel plus ADT, ARPI plus ADT, or monotherapy for ADT alone.

Overall survival (OS) and radiographic progression-free survival (rPFS) outcomes were collected. OS as primary endpoint, and rPFS as secondary endpoint, were analyzed separately in high- and low-volume patients. Additional subgroup analyses accounted for timing of metastases categorized as high-volume/synchronous, high-volume/metachronous, low-volume/synchronous, and low-volume/metachronous disease.

Triplet combinations prolonged significantly OS and rPFS in high-volume disease (P-score 0.99), and high-volume/synchronous disease (P-score 0.99). ARPI/ADT doublets performed best in low-volume patients (P-score 0.94), and low-volume/metachronous (P-score 0.99). In the high-volume/metachronous population, triplets, and doublets were equally effective.

The results provide collective evidence for treatment selection based on disease volume and timing of metastasis with strongest survival benefits of triplets for high-volume/synchronous mHSPC patients and of ARPI doublets for low-volume disease.