Presentation Authors: Luca Boeri*, Vidit Sharma, Matteo Soligo, Igor Frank, Stephen A. Boorjian, R. Houston Thompson, Matthew Tollefson, Robert Tarrell, Fernando J. Quevedo, John C. Cheville, R. Jeffrey Karnes, Rochester, MN
Introduction: Current guidelines recommend â‰¥3 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). The impact of suboptimal NAC dosing on survival outcomes after radical cystectomy (RC) has been poorly investigated. We aimed to assess the prevalence of and factors association with receiving suboptimal NAC and its impact on survival outcomes in MIBC patients treated with RC.
Methods: We reviewed 1441 patients treated with NAC and/or RC for cT2-cT4N0M0 BC. Patients were segregated into three groups: suboptimal NAC ( < 3 cycles of cisplatin-based NAC or non-cisplatin-based regimen); optimal NAC; and no NAC. Clinical characteristics were compared among groups. Comorbidities were scored with the Charlson Comorbidity Index (CCI). Complete pathological response to NAC was defined as ypT0N0. Logistic regression analyses tested the association between clinical variables and the odds of receiving suboptimal NAC. To adjust for potential baseline confounders, propensity-score matching was performed. Pathologic outcomes were compared between groups and Cox regression analyses tested risk factors associated with recurrence, overall and cancer specific survival.
Results: Before matching, 251 (17.4%) and 86 (6.0%) patients received optimal NAC and suboptimal NAC while 1104 (76.6%) underwent upfront RC. Low eGFR values (p < 0.001), CCIâ‰¥1 (p=0.02) and ECOGâ‰¥1 (p=0.02) were associated with the administration of a suboptimal NAC. After matching, 158 (38.3%), 85 (20.6%) and 169 (41.1%) patients were in the optimal NAC, suboptimal NAC and no NAC group. Positive nodal status was more frequently found in the suboptimal (37.6%) and in the no NAC group (28.9%) than in the optimal NAC group (22.7%) (p=0.038). The optimal NAC group achieved higher rates of complete pathological response as compared to the suboptimal group (26.1% vs. 15.3%; p=0.03). Five-year RFS (p=0.013) and CSM-free rates (p < 0.001) were higher for the optimal than suboptimal and no NAC group. Multivariable analysis showed that, suboptimal NAC (HR 1.74; p=0.015) and no NAC (HR 1.51; p=0.034) were both associated with poorer RFS and worse OS (HR 1.69; p=0.021 and HR 1.60; p=0.023) as compared to optimal NAC.
Conclusions: One out of four MIBC patients received a suboptimal NAC regimen before RC. Receiving a suboptimal NAC regimen was associated with worse disease recurrence and survival outcomes following RC, as compared to an optimal NAC regimen.