Long-Term Outcomes of Neoadjuvant Chemotherapy (NAC) Prior to Bladder-Sparing Trimodality Therapy (TMT) for Patients With Muscle-Invasive Bladder Cancer (MIBC).

BACKGROUND

Neoadjuvant chemotherapy (NAC) followed by bladder-sparing trimodality therapy (TMT) is an emerging treatment option for selected patients with muscle-invasive bladder cancer (MIBC), but long-term outcome data remain limited.

PATIENTS AND

METHODS

MIBC patients treated with 3-4 cycles of cisplatin-based NAC followed by TMT (maximal TURBT and concurrent radiation with weekly cisplatin) at 2 Canadian cancer centers from 2008 to 2017 were retrospectively reviewed. This updated analysis assessed median disease-free survival (DFS), overall survival (OS), bladder-intact DFS (BI-DFS), and metastasis-free survival (MFS) using Kaplan-Meier methods.

RESULTS

The study cohort included 56 patients (79% male; median age 72 [range, 45-87]) with stage II (59%), stage III (36%), and node-positive disease (13%); 38% had mixed histology. At baseline, 24% had eGFR < 60 mL/min/1.73 m², and 25% had hydronephrosis. NAC completion rate was 95%. All patients completed radiotherapy, and 88% received > 60% of planned concurrent cisplatin. After a median follow-up of 91 months, 23 patients (41%) recurred, including 11 local recurrences (20%), 8 requiring salvage cystectomy (14%), and 12 distant recurrences (21%). Median DFS was 48.9 months (95% CI, 25.3-73.4), and median OS was 96.5 months (95% CI, 56.6-126.4). Patients without residual tumor on post-NAC cystoscopy (31/43 patients) had numerically longer median DFS (73 months) and OS (126 months).

CONCLUSIONS

Cisplatin-based NAC followed by TMT can provide durable disease control in selected patients with MIBC, including those with high-risk features downstaged by NAC. Prospective studies integrating novel systemic therapies and biomarkers, including ctDNA and urinary tumor DNA, may further optimize bladder-sparing approaches.