Introduction:

Background: There are approximately 400,000 new cases of bladder cancer worldwide, with 75% of patients having non-muscle-invasive bladder cancer ( NMIBC), either above the urothelial basement membrane ( Ta and carcinoma in situ) or invasive into the lamina propria ( T1). High grade T1 bladder cancer is the most invasive of the NMIBC, with a significant proportion of patients experiencing upstaging at the time of surgery, with long-term rate of cancer specific mortality reaching up to 34%.

Because T1 can exhibits such stark variability in biologic and histopathologic characteristics, we examined the clinical differences in mortality and recurrence-free survival in patients diagnosed with non-full thickness stage T1 bladder compared patients with full-thickness lamina propria stage T1 and stage T2 cancer.

Methods:

We identified 2786 bladder cancer patients who underwent transurethral resection of bladder tumor ( TURBT) at our institution between 1995 to 2015. Patients with pure transitional carcinoma only were included in the analysis, with adequate follow up, and presence of clearly visible detrusor muscle in the initial resection. Two pathologists independently reviewed the slides.

Stage T1 bladder tumors were subclassified into two groups based on proximity of the tumor to the detrusor muscle: the advanced T1 (A-T1) tumor group, comprised of tumors that invaded the full thickness of lamina propria and were histologically immediately adjacent to but not demonstrably invasive into the detrusor muscle (DM); and the superficial T1 (S-T1) group, comprised of tumors that invaded the lamina propria but were not immediately adjacent to detrusor muscle.

154 patients were selected for the study, classified as S-T1 (n=79), A-T1 (n=20) and T2 (n=55). The variables were compared between the 3 groups using Fisher’s exact test, Chi-square test and Kruskal-Wallis. Recurrence free survival was assessed using Kaplan-Meier (KM)method and compared with the log-rank test.  All tests were 2-sided and p<0.05 was considered statistically significant.

Results:

The characteristics of 154 patients included in the study are summarized in Table 1. Only 11(25%) of patient underwent neoadjuvant chemotherapy prior to cystectomy, with additional 16 (36.4%) undergoing adjuvant therapy. Compared to S-T1 patients, A-T1 and T2 patients experienced an increased rate of mortality [25(31.6%)vs 10(50%) vs 30(54.5%), p=0.023) during the follow up period.  Patients with A-T1 disease experienced worst survival out of the three cohorts, as evidence by Kaplan Meier curve, with only 28% (95% CI 13-54%) survival at 60 months after the diagnosis, as compared to 68% (95% CI 53-79%) in S-T1 and 49%(95% CI 35-62) in T2 disease.  When evaluating risk factors responsible for increased morality, age was found to be associated with increased risk of death with HR 1.054(1-026-1.083), while CIS, multifocality, and gender were not found to be predictors for worse outcomes. S-T1 was found to be protective with HR 0.346(0.161-0.743), as compared to A-T1 and T2 disease for mortality.

Conclusion:

In conclusion our data points to strong evidence that increased depth of tumor invasion in T1 disease is a strong risk factor for increased mortality and decreased recurrence free survival.

Funding: N/A