Androgen Receptor Pathway Inhibitors for Metastatic Hormone-Sensitive Prostate Cancer Outside of Randomized Controlled Trials: A Systematic Review and Meta-Analysis of Prognostic Factors in Real-World Analyses

We aimed to analyze prognostic factors for overall survival (OS) and progression-free survival (PFS) in real-world patients treated with androgen deprivation therapy (ADT) combined with androgen receptor pathway inhibitors (ARPI) for metastatic hormone-sensitive prostate cancer (mHSPC). A systematic literature search was conducted in MEDLINE, Embase, and Web of Science in October 2025. Eligible studies examined prognostic factors for OS or PFS in patients with mHSPC receiving ARPI plus ADT using real-world data. To minimize the impact of confounding, we included only multivariable-adjusted estimates in the meta-analysis. Pooled hazard ratios (HRs) were calculated using a random-effects model and presented on forest plots. Risk of bias was evaluated using the QUIPS tool (CRD420251239659). Sixteen retrospective observational studies, comprising 3773 patients with mHSPC, were included. Poor PS (poor vs. good; HR 1.74, 95% CI 1.32-2.28, 5 studies, n = 1553), low haemoglobin (low vs normal; HR 1.75, 95% CI 1.03-2.97, 2 studies, n = 491), high LDH (high vs. normal; HR 1.8, 95% CI 1.14-2.85, 3 studies, n = 576), and ISUP GG5 (5 vs. ≤4: HR 2.21, 95% CI 1.53-3.21, 4 studies, n = 1221) were independently associated with worse OS. High EOD (≥1 or 0; HR 1.80, 95% CI 1.14-2.84, 2 studies, n = 330) was independently associated with worse PFS. The main bias was treatment selection bias inherent to retrospective studies. Limitations include residual confounding and heterogeneity in outcome definitions and prognostic factor measurements. Specific patient- and tumor-related factors are significantly associated with prognosis in patients with mHSPC treated with ARPI combination therapy. These factors may help identify patients who require closer monitoring and treatment adjustment (ie, escalation or de-escalation) as part of shared decision-making.