Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy

This study focused on patients with muscle-invasive bladder cancer initially planned for neoadjuvant systemic therapy followed by cystectomy, but who later declined cystectomy or other definitive local therapy, opting for conservative management. This retrospective analysis aimed to assess disease and bladder-preservation outcomes in this specific cohort. The therapeutic approach involved maximal transurethral resection of the bladder tumor followed by either neoadjuvant chemotherapy or pembrolizumab. The primary objective was to evaluate the efficacy of these treatments and identify potential predictors for optimal patient outcomes. The preliminary findings suggest that pembrolizumab may offer superior outcomes compared to standard chemotherapy. Notably, patients achieving clinical complete remission after neoadjuvant treatment demonstrated significantly improved survival rates. These results may influence future therapeutic recommendations, advocating for more tailored and conservative approaches to managing muscle-invasive bladder cancer in patients unwilling to undergo cystectomy or other definitive local therapies. Bladder preservation, particularly following neoadjuvant complete remission, appears effective, and pembrolizumab emerges as a promising option for those unsuitable for chemotherapy. This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.