Transient PSA Suppression Without Survival Benefit: Real-World Comparative Effectiveness of Cabazitaxel Plus Carboplatin in Metastatic Castration-Resistant Prostate Cancer (mCRPC)

BACKGROUND: Platinum-based intensification has emerged as a potential strategy in metastatic castration-resistant prostate cancer (mCRPC). However, its real-world effectiveness remains uncertain. METHODS: We conducted a retrospective cohort study using the TriNetX Research Network. Adult with mCRPC treated with cabazitaxel with or without carboplatin were identified. Propensity score matching (1:1) was performed using demographic, clinical, and laboratory variables. Primary outcomes included overall survival (OS) and prostate- specific antigen (PSA) suppression, defined as PSA response (<4 ng/mL), intermediate (4-20 ng/mL), and high (>20 ng/mL) assessed at 6 months and 1 year. Secondary outcomes included treatment-related toxicities and healthcare utilization. RESULTS: After matching, 1,618 patients were included (809 per cohort). Baseline PSA was comparable between groups (median 22.5 vs 21.9 ng/mL). At 6 months, combination therapy achieved significantly greater PSA response (<4 ng/mL: 13.2% vs 9.0%; RR 1.47; 95% CI, 1.11-1.94; p=0.007). By 1 year, this difference was no longer significant (14.8% vs 14.2%; p=0.68). No OS difference was observed (median OS 319 vs 280 days; HR 0.97; p>0.5). Hematologic toxicities were more frequent with combination therapy. CONCLUSIONS: In this large, biomarker unselected real-world cohort, carboplatin added to cabazitaxel produced significantly greater PSA response at 6 months, resolving by 1 year, and was not accompanied by an OS benefit. Given the higher hematologic toxicity, these results support a selective rather than routine role for platinum intensification in mCRPC.