Comparative efficacy and safety of carboplatin-based versus cisplatin-based chemotherapy in muscle-invasive and advanced bladder cancer: A systematic review and meta-analysis.

BACKGROUND

Cisplatin-based chemotherapy is the standard of care for muscle-invasive and advanced bladder cancer, but its significant toxicity renders approximately 30-50% of patient ineligible. Carboplatin is widely used as a substitute; however, its comparative efficacy and safety remain controversial due to fragmented and inconsistent evidence. This meta-analysis aims to compare survival outcomes, response rates, and toxicity profiles between carboplatin- and cisplatin-based regimens.

METHODS

We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO: CRD420251249371). MEDLINE, Embase, Cochrane Library, and Web of Science were searched from inception to December 2025 for studies comparing carboplatin-based versus cisplatin-based chemotherapy and restricting study populations to patients with bladder cancer only. This strict selection criterion was applied intentionally to ensure homogeneity. Outcomes included overall survival (OS), cancer-specific survival (CSS), objective response rate (ORR), pathological complete response (pCR) and adverse events (AEs). Risk of bias was assessed using RoB 2 (RCTs) and ROBINS-I (observational studies). Data were pooled using random-effects models. Heterogeneity was quantified using I² statistics.

RESULTS

Eleven studies (2 RCTs, 9 cohort studies; n = 2,543 patients) were included. Compared to cisplatin-based regimens, carboplatin-based regimens were associated with worse OS (HR = 1.30, 95% CI: 1.11-1.52; I² = 47%) and CSS (HR = 1.79, 95% CI: 1.39-2.32; I² = 16%). This survival disadvantage was pronounced in palliative settings (OS: HR = 1.27; 95% CI, 1.08-1.50; I² = 0%; CSS: HR = 1.79; 95% CI, 1.16-2.77; I² = 0%) but not significant in neoadjuvant settings (OS: HR = 1.15; 95% CI, 0.97-1.37; I² = 26%; CSS: HR = 1.86; 95% CI, 0.93-3.69; I² = 70%; pCR: RR = 0.92; 95% CI, 0.70-1.22; I² = 0%). Carboplatin is associated with significantly lower gastrointestinal toxicity (RR = 0.30; 95% CI, 0.15-0.62; I² = 0%). No significant differences were observed in hematologic toxicity (RR = 1.27; 95% CI, 0.37-4.30; I² = 75%) or grade 3-4 adverse events (RR = 0.61; 95% CI, 0.24-1.55; I² = 87%).

CONCLUSIONS

Based largely on observational studies, this study suggests that cisplatin is associated with better survival than carboplatin in bladder cancer, particularly in palliative setting. In the neoadjuvant setting, no significant difference was found while this does not imply equivalence. Carboplatin offers lower gastrointestinal toxicity and remains an option for cisplatin-ineligible patients. However, our strict selection excluded pivotal studies enrolling mixed urothelial carcinoma limits generalizability to the broader urothelial cancer population. A less strict selection that included such studies might alter effect estimates. Future RCTs with broader inclusion criteria are needed to confirm our findings.