The Response of Variant Histology Bladder Cancer to Intravesical Immunotherapy Compared to Conventional Cancer

Abstract

BackgroundHigh-grade urothelial carcinomas (UCs) often show foci of variant differentiation. There is limited information in the literature about the response of these variant urothelial tumors to immunotherapy with bacillus Calmette–Guerin (BCG). We compared the response, to treatment with BCG, of UC containing glandular, squamous, nested, and micropapillary types of differentiation to response of conventional non-muscle invasive high-grade UC.MethodsA total of 100 patients were diagnosed with variant histology urothelial cancer between June 1995 and December 2013. Forty-one patients with Ta or T1, confirmed by second look biopsies, received immunotherapy with BCG. Fourteen patients in this group were diagnosed with micropapillary differentiation, 13 patients with squamous differentiation, 9 patients with glandular differentiation, and 7 patients with nested variants. The control group included 140 patients with conventional high-grade UC. Both groups have been treated and followed similarly.FindingsPatients with variant tumors had similar clinical features to patients with conventional disease, including age, male to female ratio, stage, the presence of Tis, and median follow-up. Patients with variant tumors had a significantly worse prognosis compared to patients with conventional high-grade UC, including 5-year recurrence-free survival (63.5 Vs. 71.5%, p = 0.05), 5-year progression (≥T2)-free survival (60 Vs. 82.5%, p = 0.002), 5-year disease-specific survival (73 Vs. 92.5%, p = 0.0004), and overall survival (66 Vs. 89.5%, 0.05).InterpretationA patient with variant bladder cancer treated with intravesical immunotherapy has a 27% chance of dying from this disease within 5 years compared to 7.5% chance for a patient with conventional high-grade UC.

Variants and new entities of bladder cancer

“…Some cases have urothelial carcinoma in situ as the only urothelial component. Cases with areas of squamous differentiation may have a less favourable response to therapy than pure urothelial carcinoma, which seems to be related to a more advanced stage at presentation …”

“…Current literature provides increasingly valuable data on the clinical significance and therapy‐related issues concerning urothelial carcinoma with variant histology compared to conventional urothelial carcinoma. In general, variant urothelial carcinoma is considered an aggressive feature as it worsens overall survival due to a higher rate of upstaging after surgery . Gofrit et al .…”

“…Gofrit et al . suggest that a patient with variant bladder cancer treated with intravesical immunotherapy has a 27% chance of dying from this disease within 5 years when compared to a 7.5% chance for a patient with conventional high‐grade urothelial carcinoma . Cohen et al .…”

“…1,22 Overall, most clinicians treat urothelial carcinoma with divergent differentiation in the same manner as conventional urothelial carcinoma, as prognosis is generally thought to be similar, and current evidence has supported this approach. [13][14][15][16][17][18][19][20]…”

“…[9][10][11][12] In recent years, improved pathological recognition and clinical understanding of these entities opened a novel paradigm in bladder cancer management based on the current understanding of how distinct variant categories can affect patient prognosis; this novel approach has impacted the process of therapy selection. [13][14][15][16][17][18][19][20] Thus, the identification of urothelial carcinoma with variant histology has important clinical implications because misdiagnosis may result in improper or unnecessarily aggressive treatment. 8 Overall, histological variants follow a more aggressive clinical course than conventional urothelial carcinoma, but conclusive data on their effect on survival are currently lacking.…”