Depth of invasion to the bladder wall as a prognostic factor and its association with circulating cell-free DNA levels in patients with muscle-invasive bladder cancer

BACKGROUND: Radical cystectomy (RC) is the standard surgical treatment for patients with muscle-invasive bladder cancer, but the prognosis is not favorable, and new prognostic factors need to be discovered. We investigated the potential of depth of invasion (DOI) as a prognostic factor in patients with muscle-invasive bladder cancer who underwent RC. Furthermore, we examined the association between preoperative levels of circulating cell-free DNA and DOI. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent RC between January 2007 and December 2017; those who received neoadjuvant chemotherapy were excluded. Depth of invasion was measured using hematoxylin-eosin–stained RC specimens. RESULTS: Of the 121 patients selected, 41 (33.9%) were eligible for analysis. The median follow-up period was 14 months and mean DOI was 17 mm (range, 2–75 mm). Long DOI (>17 mm) was significantly associated with shorter progression-free survival (hazard ratio, 14.5; 95% confidence interval, 3.9–53.97, p < 0.0001) and cancer-specific survival (hazard ratio, 18.97; 95% confidence interval, 4.04–88.99, p = 0.0002) compared with short DOI. Multivariate analysis revealed that DOI was an independent risk factor for cancer-specific survival. The levels of circulating cell-free DNA were significantly higher in patients with a longer DOI than in those with short DOI (65 vs. 20 ng/mL, respectively; p = 0.028). CONCLUSIONS: Depth of invasion predicted with levels of circulating cell-free DNA and thus could be a useful prognostic factor.