Chemotherapy regimen and cisplatin dose effects on survival in neoadjuvant treatment of urothelial muscle-invasive bladder cancer.
Year: 2025
Type: conference-abstract
Abstract: 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.
Source: Journal of Clinical Oncology
Authors: Mateusz Malik, Maciej Różycki, Zbyszko Chowaniec, Marek Gelej, Jacek Ornat, Krzysztof Tupikowski, Adam Maciejczyk, Piotr Jacyk, Barbara Radecka, Dawid Sigorski, Tomasz Lewandowski, Katarzyna Czerko, Lubomir Bodnar, Anna Kopczyńska, Rodryg Ramlau, Barbara Iwanik, Ewelina Kołodziejska, Radosław Piszczek, Zenona Jabłońska, Bożena Cybulska-Stopa
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4410816407