Significance of lymphovascular invasion in organ-confined, node-negative urothelial cancer of the bladder: data from the prospective p53-MVAC trial.

OBJECTIVES: • To investigate the association between lymphovascular invasion (LVI) and clinical outcome in organ-confined, node-negative urothelial cancer of the bladder (UCB) in a post-hoc analysis of a prospective clinical trial. • To explore the effect of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) on outcome in the subset of patients whose tumors exhibited LVI.PATIENTS AND METHODS: • Surgical and tumor factors were extracted from the operative and pathology reports of 499 patients who had undergone radical cystectomy (RC) for pT1-T2 N0 UCB in the p53-MVAC trial (SWOG 4B951/NCT00005047). • The presence or absence of LVI was determined by pathologic examination of transurethral resection or RC specimens. • Variables were examined in univariate and multivariate Cox proportional hazards models for associations with time to recurrence (TTR) and overall survival (OS).RESULTS: • Among 499 patients with a median follow-up of 4.9 years, a subset of 102 (20%) had LVI-positive tumors. Of these, 34 patients had pT1 and 68 had pT2 disease. • LVI was significantly associated with TTR with a hazard ratio (HR) of 1.78 (95% confidence interval [CI]: 1.15 to 2.77; number of events [EV] = 95; p = 0.01) and with OS with a HR of 2.02 (95% CI: 1.31 to 3.11; EV = 98; p = 0.001) after adjustment for pathologic stage. • Among 27 patients with LVI-positive tumors who were randomized to receive adjuvant chemotherapy, receiving MVAC was not significantly associated with TTR (HR 0.70; 95% CI: 0.16 to 3.17; EV = 7; p = 0.65) or with OS (HR: 0.45; 95% CI: 0.11 to 1.83; EV = 9; p = 0.26).CONCLUSIONS: • Our post-hoc analysis of the p53-MVAC trial revealed an association between LVI and shorter TTR and OS in patients with pT1-T2N0 disease. • The analysis did not demonstrate a statistically significant benefit of adjuvant MVAC chemotherapy in patients with LVI, although a possible benefit was not ruled out.