Does Chemo-Radiotherapy Improve Survival Outcomes vs. Radiotherapy Alone for High-Grade cT1 Urothelial Carcinoma of the Bladder?

Abstract

<h3>Purpose/Objective(s)</h3> High-grade cT1 (HGT1) urothelial carcinoma of the bladder (UC) is an aggressive disease with a 4-year cancer-specific mortality of 36% in a large cystectomy series. NCCN guidelines recommend radical cystectomy as the preferred treatment for patients with (1) BCG-naive HGT1 with high-risk features or (2) for HGT1 disease that is BCG unresponsive or intolerant. Definitive concurrent chemoradiotherapy (CRT) has emerged as a promising bladder-sparing alternative treatment for HGT1 with the recent presentation of the single-arm RTOG 0926 trial. However, while there is level 1 evidence that CRT is superior to radiotherapy (RT) alone for muscle-invasive bladder cancer (MIBC), there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT for patients with HGT1 bladder cancer. <h3>Materials/Methods</h3> Patients with cT1N0M0, high-grade urothelial carcinoma diagnosed between 2004-2017 and treated with transurethral resection of the bladder tumor followed by RT alone or concurrent CRT were identified in the National Cancer Database (NCDB). All patient received a cumulative RT dose ≥ 50 Gy. Patients with a Charlson-Deyo comorbidity index (CDCI) score > 1 or missing key information were excluded. Propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) between groups. Covariables included age, race, ethnicity, gender, year of diagnosis, CDCI score, insurance status, educational and socioeconomic metrics, and treatment at an academic center. <h3>Results</h3> A total of 192 patients with HGT1 UC were treated with: (<i>i</i>) RT alone (n = 78) or (<i>ii</i>) CRT (n = 114). Median age was 81 (range: 50-90), and 70% were male. The median tumor size was 4.0 cm (range: 0.4-10.5 cm). The median follow-up time was 46 months (range: 10-168 months). The mean radiation dose was 62.4 Gy (SD: ±5 Gy) and 63.2 Gy (SD: ±12 Gy) in the RT and CRT cohorts, respectively. Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone [Hazard Ratio (HR): 0.56, 95% Confidence Interval (95% CI): 0.36-0.89, <i>p</i> = 0.012]. Female gender was associated with worse OS (HR: 1.75, 95% CI 1.16-2.66, p = .008). 4-year OS for the RT alone versus CRT arm was 22% and 38%, respectively. <h3>Conclusion</h3> For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone. These results complement the findings of RTOG 0926 showing the promise of CRT for the treatment of HGT1 disease and support the decision by NRG Oncology investigators to omit RT alone as a treatment arm in the successor trial to RTOG 0926 for HGT1 disease.