VARIANT HISTOLOGIC DIFFERENTIATION IN BLADDER CANCER TREATED WITH RADICAL CYSTECTOMY: INCIDENCE AND LONG TERM SURVIVAL IN A SINGLE INSTITUTION STUDY.

INTRODUCTION AND OBJECTIVES: Bladder cancer (BCa), may present with variant morphologic features that deviate from the urothelial common aspect. These characteristics that can be defined as pure or mixed variants may have prognostic and therapeutic implications. METHODS: We retrospectively evaluated histopathological data from 1,067 BCa patients treated with radical cystectomy (RC) and PLND for BCa between 1990 and 2013 at a single tertiary care referral center. All specimen were evaluated by dedicated uropathologists. Uni- and multivariate Cox regression analyses tested the impact of different histopathological variant CSM (cancer specific mortality) and OM (overall mortality) after accounting for age at surgery, pathological N stage, use of perioperative chemotherapy, number of positive nodes, number of removed nodes, positive surgical margin, pathological T stage, lymph vascular invasion, use of adjuvant chemotherapy. RESULTS: Of 1,067 patients, 756 (70.9%) harbored pure urothelial BCa while 311 (29.1%) were found to have a variant. Of these, 202 (64.9%) had a mixed variant and 109 (35.1%) a pure variant. Considering uncommon variants, 21 (6.8%) were sarcomatoid, 10 (3.2%) lymphoepitelial, 19 (6.1%) small cell, 4 (1.3%) plasmacitoid, 2 (0.6%) nested, 109 (35.0%) squamous, 89 (28.6%) micropapillary, 23 (7.4%) glandular and 34 (10.9%) multiple mixed. With a median follow up of 65 months, CSM and OM were recorded in 365 (34.2%), 451 (42.3%) patients, respectively. The OM was 47% vs. 53% vs. 59% for pure urothelial vs. mixed vs. pure variants, respectively (Log rank p\ubc0.011). The 5-years CSM was 44% vs. 47% vs. 53% for pure urothelial vs. mixed vs. pure variants, respectively (Log rank p\ubc0.019). At MVA Cox regression analyses, the presence of pure histological variant was associated with higher CSM (HR: 1.60, p<0.005) and OM (HR: 1.55, p<0.004) as compared to pure urothelial cancer. However, no differences were recorded when mixed variants vs. pure transitional were analyzed (all p>0.3). In details, neuroendocrine (HR 4.30, CI 2.02-9.13, p<0.001), micropapillary (HR: 4.35, p\ubc0.02) and multiple mixed (HR: 1.73; p