Prognostic value of T1 substaging on oncological outcomes in patients with non-muscle-invasive bladder urothelial carcinoma: a systematic literature review and meta-analysis

PURPOSE: To evaluate the prognostic value of substaging on oncological outcomes in patients with T (or pT1) urothelial carcinoma of the bladder. METHODS: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on March 2019 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The pooled disease recurrence (DR) and disease progression (DP) rate in T1(or pT1) patients were calculated using a fixed or random effects model. RESULTS: Overall 36 studies published between 1994 and 2018 including a total of 6781 bladder cancer patients with T1(or pT1) stage were selected for the systematic review and meta-analysis. Twenty-nine studies reported significant association between tumor infiltration depth or muscularis mucosa (MM) invasion and oncological outcomes. Totally 12 studies were included in the meta-analysis. MM invasion (T1a/b/c [or pT1a/b/c] or T1a/b [or pT1a/b] substaging system) was associated with DR (pooled HR: 1.23, 95%CI: 1.01–1.49) and DP (pooled HR: 2.61, 95%CI: 1.61–4.23). Tumor infiltration depth (T1 m/e [or pT1 m/e] substaging system) was also associated with DR (pooled HR: 1.49, 95%CI: 1.11–2.00) and DP (pooled HR: 3.29, 95%CI: 2.39–4.51). CONCLUSIONS: T1(or pT1) substaging in patients with bladder cancer is of prognostic value as it is associated with oncologic outcomes. Inclusion of this factors into the clinical decision-making process of this heterogeneous tumor may improve outcomes, while avoiding over- and under-treatment for T1(or pT1) bladder cancer.