Meta-analysis links aggressive-variant prostate cancer to poorer survival
A meta-analysis of 40 studies found aggressive-variant prostate cancer was linked to shorter progression-free and overall survival. Platinum-based chemotherapy showed higher response rates than non-platinum regimens.
Aggressive-variant prostate cancer was associated with poorer survival outcomes than non-AVPC in a meta-analysis of 40 studies. Platinum-based chemotherapy outperformed non-platinum regimens, with higher objective response rates in the overall AVPC cohort and in c-AVPC/m-AVPC and t-NEPC subgroups.
Aggressive-variant prostate cancer (AVPC) is an umbrella term that encompasses clinically defined AVPC (c-AVPC), molecularly defined AVPC (m-AVPC), and treatment-related neuroendocrine PC (t-NEPC), which represent a spectrum of metastatic castration-resistant PC phenotypes with poor clinical outcomes. Despite its clinical relevance, AVPC definitions remain heterogeneous and treatment guidelines are lacking.
A systematic literature search of PubMed, Embase, and Scopus up to September 15, 2025 identified 1,518 records, and 40 studies, including 10 abstracts, were analyzed. In comparison to non-AVPC, c-AVPC/m-AVPC was associated with shorter progression-free survival (hazard ratio 2.72, 95% confidence interval 1.54-4.81; I2 = 0%) and overall survival (hazard ratio 2.81, 95% confidence interval 1.87-4.22; I2 = 36%).
Platinum-based chemotherapy was associated with higher objective response rates than non-platinum regimens in the overall AVPC cohort (46% vs 19%; p < 0.01), in c-AVPC/m-AVPC (41% vs 16%; p = 0.04), and in t-NEPC (49% vs 22%; p < 0.01). In c-AVPC/m-AVPC, platinum-based chemotherapy was associated with longer progression-free survival (hazard ratio 0.39, 95% confidence interval 0.24-0.62; I2 = 0%) and overall survival (hazard ratio 0.40, 95% confidence interval 0.23-0.68; I2 = 0%) according to evidence from mixed-design studies.
For t-NEPC, data were insufficient for meta-analytic comparison of progression-free survival and overall survival by platinum-based chemotherapy use. The report said future studies should focus on molecularly informed classification frameworks that include genomics, histology, and advanced imaging to optimize patient stratification and guide targeted therapies.
The analysis was published in European Urology Oncology on February 10, 2026 as an epub ahead of print.