Predictive value of clinical complete response to neoadjuvant chemotherapy in trimodality therapy for muscle invasive bladder cancer.

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Background: For patients with muscle-invasive bladder cancer (MIBC) treated with bladder-preserving trimodality therapy (TMT), the importance of response to neoadjuvant chemotherapy (NACT) is not known. Methods: The study cohort was drawn from a prospectively maintained institutional database of patients with non-metastatic MIBC treated with TMT from 2011 onwards. Eligibility criteria included NACT before TMT, pre- and post-NACT imaging available for review, and a minimum of 3 months of follow-up after TMT. Using pre- and post-NACT cystoscopy and imaging, each patient’s response was categorised as either clinical complete response (cCR), i.e. absence of any visible residual disease, or non-cCR, i.e. visible residual disease or suspicious thickening. All patients received 64Gy to the bladder using ‘plan of the day’ adaptive IMRT with daily image guidance and concurrent weekly chemotherapy. Bladder-intact event-free survival (BIEFS; time to invasive local recurrence, nodal or metastatic disease, any-cause cystectomy, or death) and overall survival (OS) were estimated from the date of completion of radiotherapy, and impact of cCR analysed using Cox proportional hazards model. Results: A total of 120 patients were analyzable (85% urothelial, 15% with variant subtype). Median age was 57 years (IQR 50-63), and most had cT2-T3 (89%) and N0 (62.5%) stage at diagnosis. NACT was predominantly 3-weekly gemcitabine and cisplatin (86.7%) for a median of 4 cycles (IQR 3-4). Post-NACT, 63% of patients attained cCR. All patients completed TMT as planned. Over a median follow up of 27 months, 35 events for BIEFS were observed. Overall 2-year BIEFS was 72.7%, significantly higher for patients with cCR vs non-cCR (80.9% vs 58.2%, p =0.04). cCR maintained statistical significance for BIEFS after adjusting for age, tumour and nodal stage [HR 0.49 (0.24- 1.0), p=0.05]. Total 22 patients died, with 2-year OS being 88% for cCR and 74% for non-cCR [HR 0.4(95% CI 0.16–0.99), p=0.05]. Conclusions: Post-NACT cCR effectively predicted improved outcomes, with significantly higher BIEFS for patients with MIBC treated with TMT.