The impact of non-urothelial variant histology on oncological outcomes following radical cystectomy

Objectives: To determine if the presence of non-urothelial variant histology (NUVH) is associated with a poorer prognosis following radical cystectomy (RC) compared to pure urothelial carcinoma (PUC). Patients and methods: A prospectively maintained database of all patients undergoing RC at a high-volume regional tertiary bladder cancer service between January 2010 and January 2017 was retrospectively analysed looking for patients with NUVH. Multivariate Cox proportional hazards regression analysis was used to determine disease recurrence, overall survival and bladder cancer-specific survival, as well as lymph node positivity. Association of tumour stage was determined using chi-squared analysis. Results: In total, 430 patients underwent RC of which 73 (17%) had NUVH and 357 (83%) had PUC. The median (range) follow-up was 45.0 (8.5–100.2) months. The presence of NUVH was associated with both increased overall (hazard ratio [HR] 1.86, 95% confidence interval [CI] 1.21–2.85) and bladder cancer-specific mortality (HR 1.81, 95% CI 1.91–3.01), as well as disease recurrence (HR 1.71, 95% CI 1.06–2.75) in multivariate analysis. Squamous cell variant was also associated with increased overall mortality (HR 1.91, 95% CI 1.16–3.13), cancer-specific mortality (HR 2.03, 95% CI 1.21–3.42) and disease recurrence (HR 2.08, 95% CI 1.23–3.52), although this was not seen in other variant subtypes. Lymph node positivity was not associated with NUVH in multivariate analysis (HR 1.28, 95% CI 0.59–2.75), but NUVH was associated with advanced tumour stage on chi-squared analysis (P < 0.001). Conclusion: Our results showed a risk of shorter survival in NUVH compared to PUC. This suggests NUVH as an independent predictor of worse outcomes. As a result, patients with NUVH should be counselled preoperatively that overall and disease-specific outcomes are worse postoperatively and about the possible need for adjuvant treatment.