Pathologic and oncologic outcomes in patients with sarcomatoid differentiation undergoing cystectomy.

OBJECTIVE To evaluate whether urothelial carcinoma with sarcomatoid differentiation is associated with a lower pathologic response rate to neoadjuvant chemotherapy and worse oncologic outcomes compared to urothelial carcinoma without variant histology among patients undergoing radical cystectomy. PATIENTS AND METHODS Patients with urothelial carcinoma undergoing cystectomy from 1995-2018 at Memorial Sloan Kettering were identified. Patients with sarcomatoid differentiation at transurethral resection or cystectomy and patients without variant histology were selected. Downstaging from ≥cT2 to ≤pT1N0 defined partial response; pT0N0 defined complete response. Recurrence-free, cancer-specific, and overall survival were modeled. RESULTS We identified 131 patients with sarcomatoid differentiation and 1,722 patients without variant histology, of whom 25 with sarcomatoid histology on biopsy and 313 without variant histology received neoadjuvant chemotherapy. Those with sarcomatoid differentiation presented with higher consensus tumor stage (94% ≥T2 vs 62%, P <0.001) and were therefore more likely to receive neoadjuvant chemotherapy (29% vs 18%, P = 0.004). We found no evidence to support a difference in partial (24% vs 31%) or complete (20% vs 24%) response between patients with sarcomatoid histology and pure urothelial carcinoma at transurethral resection (p=0.6). Among patients with sarcomatoid differentiation, five-year recurrence-free survival was 55% (95% CI 41%-74%) among patients receiving NAC and 40% (95% CI 31%-52%) among patients undergoing cystectomy alone (p=0.1). Adjusting for stage, nodal involvement, margin status, and receipt of neoadjuvant chemotherapy, sarcomatoid differentiation was associated with worse recurrence-free (HR 1.83, 95% CI 1.39-2.40), disease-specific (HR 1.66, 95% CI 1.24-2.23), and overall survival (HR 1.38, 95% CI 1.06-1.78). CONCLUSIONS Sarcomatoid differentiation was associated with higher stage at presentation and independently associated with worse survival. Given similar pathologic response rates if sarcomatoid differentiation is detected at initial resection, and greater survival among patients receiving NAC, treatment with NAC appears warranted. Other drivers of the poor outcomes of this histology must be investigated.