Chemotherapy regimen and cisplatin dose effects on survival in neoadjuvant treatment of urothelial muscle-invasive bladder cancer.

e16579 Background: Neoadjuvant chemotherapy (NACT) in patients (pts) with muscle-invasive bladder cancer (MIBC) significantly improves treatment outcomes. Widely used NACT regimen based on 3-4 cycles of gemcitabine and cisplatin (GC) before radical cystectomy (RC) remained the standard of care until the complete results of the VESPER trial, which demonstrated the superiority of 6 cycles of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in terms of progression-free survival (PFS), complete pathological responses (pCR) and overall survival (OS). In most clinical trials, pts with clinically positive lymph nodes (N+ according to TMN) were underrepresented. The aim of the study is to compare the effectiveness and safety of the mentioned NACT regimens in real medical practice. Methods: Pts from 7 urooncology hospitals in Poland with MIBC stage ≥T2, cM0 treated with NACT GC or ddMVAC (11/2016-09/2024) were included. Pts from clinical trials were excluded. Complete clinical data were collected. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square or Fisher's tests were used for comparison between groups. Data cut-off was 31/12/2024. Results: Of the 261 pts treated with NACT, 232 were included in the analysis: 132 (57%) received GC, 100 (43%) ddMVAC). There were 55 (24%) women in the study groups, the median age was 67, cT2N0: 90 (39%), N+: 61 (27%), baseline anemia of any grade: 107 (48%). In the GC group, there were significantly more ECOG performance status (PS) 2 pts, p=0.0076, other variables did not differ significantly. Median total dose of cisplatin (MTDC) was significantly higher in ddMVAC group than in GC group (280 vs 210 mg/m2), p=0.0024. Median chemotherapy period was significantly longer in GC pts: 9 vs 6.3 weeks for ddMVAC, p=0.0007. RC was not performed in 35 (15%) of pts due to adverse events (AEs), progression, or withdrawal of consent. More objective pathological responses were achieved in the ddMVAC vs GC pts, 42 vs 14%, p<0,0001, however, there were no differences in clinical response. Significant difference in mOS between GP and ddMVAC group was observed: 27 vs 39m, p=0.0203. In univariate analysis, a significant advantage was also observed for MTDC ≥250mg/m2, p=0.0093; ECOG PS 0, p=0.0018; RC, p=0.01; R0 resection, p=0.001; and pCR, p<0.0001 in terms of OS. OS did not differ significantly between cT2N0 or >cT2N0 pts, p=0.3. Multivariate analysis confirmed a statistically significant OS benefit for ECOG PS 0, higher MDTC and pCR. More hematological AEs occured in the GC vs ddMVAC group: 98% vs 84%, p=0.0007. Conclusions: The use of NACT with the ddMVAC in MIBC pts showed a statistically significant improvement of OS compared to GC with favorable toxicity. The study indicates that the best prognosis is for pts with ECOG PS 0 who received a higher MTDC (preferably in the ddMVAC regimen), responded to NACT and underwent radical surgery regardless of the primary clinical stage of T and N.