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

CONTEXT With new treatment strategies approved in metastatic hormone-sensitive prostate cancer (mHSPC), heterogeneity across trials hinders the physicians’ choice for first-line treatment. OBJECTIVE 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). INTERVENTION Eleven randomized controlled trials (RCTs) published until October 30th, 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS 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-volume 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. EVIDENCE SYNTHESIS 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. CONCLUSIONS 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.