Clinical efficacy of current treatments for high-volume metastatic hormone-sensitive prostate cancer: a systematic review and network meta-analysis

Abstract

Abstract Background Several randomized controlled trials (RCTs) demonstrated a significant survival benefit of novel treatment regimens compared with androgen deprivation therapy (ADT) for metastatic hormone-sensitive prostate cancer (mHSPC), especially in high-volume disease (HVD, CHAARTED defined). As an influence on poor prognosis, the treatment for patients with HVD, especially visceral metastasis (VM) needed to be distinguished from mHSPC. This study was conducted to rank the treatment options for patients with HVD and VM, respectively, according to the latest data. Methods We synthesized current evidence based on well-designed RCTs. Only phase III trials were included. A Bayesian network meta-analysis was conducted by using R-4.2.3, and the pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) with a 95% credible interval (CI) were calculated. Note that the definitions of PFS were various. The ranking plots were generated. OR of adverse events was also calculated and presented. This study was registered in the International Prospective Register of Systematic Reviews (CRD42023416334). Results Eleven RCTs were included through Pubmed, Embase and Cochrane. In HVD patients, all combination therapies can improve OS and PFS. Among them, The HR for Darolutamide (Daro) + Docetaxel (Doc) + androgen deprivation therapy (ADT) was most significant over ADT in both OS and PFS (hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.39–0.63; HR: 0.25; 95% CI: 0.19–0.31). In patients with visceral metastasis, adding novel hormonal agents (NHAs) to ADT showed better survival outcome. But in analysis of treatment ranking, not alike the outcome of high-volume disease, Doc + ADT seems ranked higher than other NHA + ADT. Almost all combination therapies lead to more grade ≥ 3 adverse events. Conclusion Triplet therapy achieved the best effect on both HVD and visceral metastasis with a tolerable adverse effect. In HVD, our findings demonstrated that any NHA, Docetaxel or triplet combination therapy was superior to ADT alone. Ranking of combination therapy differs between patients with HVD and visceral metastases. In patients with visceral metastasis, chemotherapy has a higher priority than novel hormonal agents. Abiraterone's efficacy ranked better compared to other NHAs but still worse than docetaxel. The sensitivity treatments of bicalutamide versus placebo lead to diversity of results.