760 Background: The Relative Dose Intensity (RDI) of neoadjuvant chemotherapy (NAC) is known to influence pathological response and survival in several solid tumours. However, its role in muscle-invasive urothelial carcinoma (MIUC) remains underexplored. This study aimed to evaluate the association between RDI of cisplatin-based (CB) NAC and pathological complete response (pCR), and its correlation with event-free survival (EFS) and overall survival (OS). Methods: We retrospectively collected data on 321 patients with cT2-cT4 ± N0-N+ MIUC of CB NAC followed by radical cystectomy across multiple centres in Italy and the UK between 2014 and 2025. RDI was defined as the ratio between the dose of chemotherapy administered and the planned dose, multiplied by the ratio between the planned duration and the actual duration of treatment, expressed as a percentage. The planned dose was 70 mg/m² of cisplatin per cycle over 4 cycles within 63 days. The primary endpoint was pCR (ypT0/ypTis); secondary endpoints included EFS and OS. To limit heterogeneity in drug delivery, only patients who received 3 or 4 cycles of NAC were included. Associations were analysed through χ² tests and Kaplan-Meier/log-rank methods. A multivariate logistic regression was performed including RDI, mEFS, mOS, cT stage, nodal status, Charlson Comorbidity Index, age, sex, performance status, nephrostomy, and histology. Results: Among 321 patients, 165 were included in the RDI-High (≥ 80%) and 156 in the RDI-Low ( < 80%) group. Median follow-up time was 26.6 months (95% CI, 23.7-29.9). Overall, 41 patients (12.8%) presented with node-positive disease and 280 (87.2%) were node-negative. The pCR rate was significantly higher in the RDI-High group compared with the RDI-Low group (47.9% vs 30.8%; p = 0.002). In multivariate logistic regression, RDI ≥80% remained an independent predictor of pCR (OR 2.68, 95% CI 1.48-4.84; p < 0.001). Similarly, RDI ≥80% was associated with a favourable trend toward improved EFS (HR 0.68, 95% CI 0.45–1.01; p = 0.057) and OS (HR 0.59, 95% CI 0.34-1.01; p = 0.055). Multivariate models were consistent with these findings. mEFS and mOS were not reached in either group. Achieving pCR was strongly associated with reduced risk of recurrence (EFS HR = 0.18, 95% CI: 0.11-0.31; p < 0.001) and death (OS HR = 0.30, 95% CI: 0.16-0.57; p < 0.001). Conclusions: These findings highlight the clinical relevance of maintaining adequate chemotherapy dose intensity to optimise neoadjuvant treatment efficacy in MIUC, given its strong association with higher pCR rates. This study demonstrates the essential impact of RDI on oncological outcomes and supports its inclusion as a stratification criterion in future neoadjuvant clinical trials.
Neola et al. (Sun,) studied this question.