Two cycles of neoadjuvant chemotherapy improves survival in patients with high-risk upper tract urothelial carcinoma.

To assess the impact of two cycles of neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high-risk cN0M0 upper tract urothelial carcinoma (UTUC), and to evaluate the efficacy of NAC in patients with localized disease (cT2 or lower).

We retrospectively analyzed high-risk cN0M0 UTUC patients who received NAC followed by surgery, compared with a matched cohort who underwent initial surgery at Fujita Health University during 2005-2019. Baseline and tumor characteristics, overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared between the cohorts. Cox proportional hazards models were used to identify predictors of survival.

There were 117 and 67 patients in the study group and the control group, respectively. Significantly higher pathological downstaging (pDS) and lower lymphovascular invasion (LVI) were observed in the study group than in the control group (48% vs. 22%, p = 0.008 and 29% vs. 46%, p = 0.045, respectively). The NAC group had significantly better 5-year OS (79% vs. 53%, p = 0.003), 5-year CSS (84% vs. 66%, p = 0.008), and 5-year RFS (80% vs. 61%, p = 0.001) than the control group. The OS benefit of NAC was observed even in patients with localized (cT2 or lower) disease (p = 0.019). Patients with LVI showed significantly worse CSS both in pathologically locally advanced (pT3 or higher) and in localized (pT2 or lower) tumors (p = 0.048 and p = 0.018, respectively). Multivariate analysis identified LVI, NAC, and pDS as independent predictors of OS. Male sex and post-NAC LVI were identified as predictors of worse survival in patients who underwent NAC.

Two cycles of NAC improved the survival of high-risk UTUC patients, even in patients with localized disease. Although two cycles of NAC appear to be effective in cN0M0 high-risk UTUC including localized disease, additional larger sample-size multicenter prospective studies comparing short-course neoadjuvant chemotherapy regimens, followed by surgery, and surgery alone are required.

BJU international. 2020 Sep 07 [Epub ahead of print]

Kenji Zennami, Makoto Sumitomo, Kiyoshi Takahara, Takuhisa Nukaya, Masashi Takenaka, Kosuke Fukaya, Manabu Ichino, Naohiko Fukami, Hitomi Sasaki, Mamoru Kusaka, Ryoichi Shiroki

Department of Urology, Fujita Health University School of Medicine, Toyoake, Japan., Department of Urology, Fujita Health University Okazaki Medical Center, Okazaki, Japan.