COMPLETE RESPONSE AFTER NEOADJUVANT CHEMOTHERAPY FOR MUSCLE-INVASIVE BLADDER CANCER: IS TIME FOR A PARADIGM SHIFT IN SURGICAL TREATMENT?

INTRODUCTION AND OBJECTIVE: In recent here, complete response (CR) to neoadjuvant chemotherapy (NAC) in bladder cancer (BCa) has questioned the role of radical cystectomy (RC) for the patients. To avoid upfront RC, bladder sparing approaches have been proposed. Nonetheless, RC morbidity may be significantly reduced by skipping pelvic lymph node dissection (PLND). So we investigated lymph nodes invasion (LNI) rate in patients exhibiting CR after NAC. Moreover, we tested whether CR status was a predictor of LNI. Finally, we investigated the association of CR with survival and metastatic progression. METHODS: Whitin our prospectively maintained database, we identified patients treated with NAC prior to RC + PLND for cT2-4acN0cM0 BCa at our institution from 2012 to 2022. CR was defined as absence (pT0) of BCa in the bladder specimen at final pathology. LNI was defined as node positivity at final pathology. First, logistic regression model tested the association between CR and LNI. Kaplan-Meier plot depicted overall survival (OS) and metastasis-free survival (MFS) according to CR status. Cox regression model tested the association between CR and survival outcomes after adjusting for lymph node density and Charlson Comorbidity Index. RESULTS: Of 157 NAC treated patients (Table 1), 63 exhibited CR (40.1%) at the final pathology. At RC, median number of lymph node removed was 26 (IQR 19-36) with an overall LNI rate of 19% (n=30). LNI rate was lower in patients harboring CR relative to their counterparts (2 [3.2%] vs 61 [29.8%], p<0.001). After adjusting for number of lymph node removed, CR reduced by 93% LNI risk (OR 0.07, 95% CI 0.01-0.25, p<0.001). At Kaplan Meier analysis, patient exhibiting CR resulted in better five-year OS (70.7 vs 52.2%) and MFS (71.3 vs 42.2%) than their counterparts, respectively. After multivariable adjustments, CR decreased the risk of overall mortality (HR 0.41 95% CI 0.22-0.78, p=0.007) and metastatic progression (HR 0.42 95% CI 0.23-0.82, p<0.001), respectively. CONCLUSIONS: According to our series, probability of LNI was extremely low (3%) in patients exhibiting CR after NAC. If similar results are supported by large multicenter series, randomized trial investigating PLND omission in a similar scenario should be run.