Risk Stratification Model to Predict High-Risk Patients for AdjuvantChemotherapy in Upper Urinary Tract Urothelial Cancer

Objective: Optimal patient selection for adjuvant chemotherapy has not been clarified in upper urinary tract urothelial cancer (UTUC). We aimed to develop a risk model to select candidates for adjuvant chemotherapy after radical nephroureterectomy (RNU). Methods: A retrospective review of 936 patients with UTUC between 1995 and 2015 who received ≥ 2 cycles of platinum-based adjuvant chemotherapy after RNU (n=213) or surgery alone (n=723) was conducted in collaborative institutions. Risk factors for cancer-specific mortality were extracted using the proportional hazard model. The survival benefit in high-risk patients was compared between the groups. Results: At a median follow-up of 1006 days (34 months), disease recurrence, cancer-specific mortality, and allcause mortality were noted in 253 (27.5%), 206 (22.0%), and 285 (30.4%) patients, respectively. On multivariate analysis, baseline serum C-reactive protein (CRP) ≥ 0.32 mg/dL (HR: 1.74, 95% CI: 1.09–2.75, p=0.0201), pathologic T stage ≥ 3 (pT>3) (HR: 2.17, 95% CI: 1.28–3.76, (p=0.0033), cN+ (HR: 2.84, 95% CI: 1.50–5.01, p=0.0021), and lymphovascular invasion (LVI) (HR: 3.94, 95% CI: 2.23–7.17, p<0.0001) were independent predictors of cancer-specific mortality (CSM) in the training set. When they were used to categorize patients into low (0-1 factor) and high-risk groups (2-4 factors), high-risk patients had significantly worse CSM than those with low-risk. In the high-risk patients, 42.3% who received adjuvant chemotherapy had significantly better CSM and all-cause mortality than those who underwent surgery alone. In high-risk patients, multivariate analysis showed adjuvant chemotherapy as an independent prognostic factor for CSM (HR: 0.52) and all-cause mortality (HR: 0.57). Conclusion: CRP, pT>3, cN+, and LVI was useful for identifying high-risk patients.