Pathological downstaging and survival after induction chemotherapy and radical cystectomy for clinically node-positive bladder cancer-Results of a nationwide population-based study.

BACKGROUND: Induction chemotherapy (IC) for clinically node-positive bladder cancer is applied without clinical evidence of improved outcome. Our objective was to compare complete pathological downstaging (pCD) and overall survival (OS) for IC versus upfront radical cystectomy (RC) in cT1-4aN1-3M0 urothelial carcinoma (UC).

METHODS: This population-based study included 659 cN+ patients treated with RC between 1995 and 2013. IC was applied in 212 (32%) patients. We defined pCD as ≤(y)pT1N0 at RC. Multivariable analyses were preformed to identify independent predictors of pCD and OS.

RESULTS: In cN1 and cN2-3 patients, 31% and 19% of patients proved to be pN0 at upfront RC. In cN1, pCD was achieved in 39% following IC versus 5% for upfront RC (P < 0.001). In cN2-3 UC, rates were 27% versus 3% (P < 0.001). Three-year OS for pCD and ypCD were 81% and 84%, respectively. Three-year OS rates were 66% versus 37% (cN1) and 43% versus 22% (cN2-3), again in favour of IC (P < 0.001). In multivariable analyses, IC was associated with pCD (Odds ratio, 14; 95% confidence interval [CI], 7.4-25) and a 53% decreased risk of death (Hazard ratio [HR], 0.47; 95% CI, 0.36-0.61). Indication bias and unequal distributions of factors associated with OS (e.g. patients proceeding to RC) limit interpretation of our results.

CONCLUSIONS: Patients with clinical nodal involvement should not be neglected. Up to 1/4 of patients with cN+ disease had pN0 at upfront RC. Moreover, IC followed by RC for clinically node-positive UC was associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.

TAKE HOME MESSAGE: IC followed by RC for clinically node-positive UC is associated with improved pathological downstaging compared with RC alone. A potential OS benefit for IC needs to be validated in a randomised trial.