Subepithelial growth patterns in urothelial carcinoma-frequency and prognostic significance

Purpose: Most urothelial carcinomas are exophytic, but some tumors exhibit subepithelial components, either in the form of endophytic growth pattern (EGP) or as von Brunn's nests involvement (VBNI). The purpose of this study was to investigate the frequency, inter-relations and clinical significance of these forms of subepithelial neoplasia in urothelial carcinoma. Patients and methods: Between June 1995 and December 2007, 760 patients (mean age of 67.5 years) underwent transurethral resection of bladder tumors in our institution, including 478, 157, and 112 patients with stage Ta, T1, and ≥T2 disease, respectively. Isolated or concomitant Tis were present in 137 (18%) patients. Median postoperative follow-up period was 53 months. Results: EGP was found in 86 cases (11.3%) and VBNI in 30 (3.9%) patients. Both forms of subepithelial growth were significantly more common in higher stage and grade tumors and were associated with each other. Multivariate analysis showed that EGP is an independent prognostic factor of stage progression (HR 4.6, P < 0.0001) and disease specific mortality (HR 2.6, P = 0.001) but not of tumor recurrence (HR 1.2, P = 0.51). VBNI was found an independent prognostic factor of tumor progression (HR 5.1, P < 0.0001), but neither of tumor recurrence nor disease specific mortality. Conclusions: Subepithelial growth is not an uncommon in bladder cancer. It is more frequent in high-grade and high-stage tumors. The findings of this study suggest that subepithelial growth carries a higher risk for stage progression (EGP and VBNI) and mortality (EGP), but not tumor recurrence.