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.