To compare the overall survival (OS) outcomes of non-muscle invasive bladder cancer (NMIBC) patients with variant histology who underwent radical cystectomy (RC) vs. bladder preservation therapy (BPT).

We investigated the National Cancer Database for NMIBC patients with variant histological features. Patients diagnosed with micropapillary, sarcomatoid, neuroendocrine, squamous, and glandular variants were identified. Inverse probability weighting (IPW)-adjusted Kaplan Meier survival curves and Cox proportional hazard models were utilized to compare OS in the setting of RC versus BPT.

A total of 8,920 (2.7%) NMIBC patients presented with variant histology, of whom 2,450 (27.5%) underwent RC, while 6,470 (72.5%) had BPT. When compared with BPT, patients who underwent RC had significantly higher 5-year OS rates for sarcomatoid (31.9% vs. 23.3%, P < 0.001) neuroendocrine (31% vs. 21.7%, P < 0.001), glandular (44% vs. 41%, P = 0.04) and squamous variants (39.7% vs 19.9%, P < 0.001). This OS benefit was not observed with micropapillary variant (43.9% vs. 53.2% P = 0.14). IPW-adjusted log-rank analysis identified RC as an independent predictor of OS for patients with sarcomatoid (hazards ratio [HR] 0.78, confidence interval [CI] 0.71-0.85, P < 0.001), squamous (HR 0.56, CI 0.53-0.59, P < 0.001), and neuroendocrine variants (HR 0.83, CI 0.76-0.91, P < 0.001), but not for micropapillary variant (HR 1.45, CI 1.24-1.7, P < 0.001).

Among NMIBC patients presenting with variant histologies, RC was associated with better OS for sarcomatoid, squamous, glandular, and neuroendocrine variants when compared to BPT. This OS survival benefit was not observed in patients with micropapillary variant suggesting a potential role for bladder preservation in such population.