Commentary on "Detection and oncological effect of circulating tumor cells in patients with variant urothelial carcinoma histology treated with radical cystectomy."

OBJECTIVES: To investigate for the presence of circulating tumor cells (CTC) in patients with variant urothelial carcinoma of the bladder (UCB) histology treated with radical cystectomy (RC), and to determine their impact on oncological outcomes.

PATIENTS AND METHODS: We, prospectively, collected data of 188 patients with UCB treated with RC without neoadjuvant chemotherapy. Pathological specimens were meticulously reviewed for pure and variant UCB histology. Preoperatively collected blood samples (7.5ml) were analyzed for CTC using the CellSearch system (Janssen, Raritan, NJ).

RESULTS: Variant UCB histology was found in 47 patients (25.0%), most frequently of squamous cell differentiation (16.5%). CTC were present in 30 patients (21.3%) and 12 patients (25.5%) with pure and variant UCB histology, respectively. At a median follow-up of 25 months, the presence of CTC and nonsquamous cell differentiation were associated with reduced recurrence-free survival (RFS) and cancer-specific survival (pairwise P ≤ 0.016). Patients without CTC had better RFS, independent of UCB histology, than patients with CTC with any UCB histology (pairwise P<0.05). In multivariable analyses, the presence of CTC, but not variant UCB histology, was an independent predictor for disease recurrence (hazard ratio = 3.45, P<0.001) and cancer-specific mortality (hazard ratio = 2.62, P = 0.002).

CONCLUSION: CTC are detectable in about a quarter of patients with pure or variant UCB histology before RC, and represent an independent predictor for outcomes, when adjusting for histological subtype. In addition, our prospective data confirm the unfavorable influence of nonsquamous cell-differentiated UCB on outcomes.