External validation of the VENUSS prognostic model to predict recurrence after surgery in non-metastatic papillary renal cell carcinoma: A multi-institutional analysis.

Recently, VENUSS (VEnous extension, NUclear Grade, Size, Stage), as a prognostic model, was defined to predict disease recurrence (DR) after curative surgery of non-metastatic papillary renal cell carcinoma (papRCC). This study aimed to validate the VENUSS prognostic model in a large multi-institutional European cohort of patients with histopathologically proven papRCC after curative surgery for non-metastatic disease. Overall, 980 patients undergoing partial or radical nephrectomy for sporadic, unilateral and non-metastatic papRCC between 1987 and 2020 were included from 7 European tertiary institutions. The primary outcome was the prediction of DR by VENUSS score and VENUSS risk groups. Chi-square, Kruskal-Wallis, Cox-regression and Kaplan-Meier survival analyses were used in statistical methods. The Concordance (C) Index was calculated to assess model's discriminatory power. The median age was 64 (IQR:55-70) years and 82.6 % (n = 809) of patients were male. Median VENUSS score was 2 (IQR: 0-4), and 62.9 % (n = 617), 23.9 % (n = 234) and 13.2 % (n = 129) of patients was classified into low, intermediate and high risk according to the VENUSS model, respectively. At a median follow-up of 48 (IQR:23-88) months, the disease recurred in 6.6%, 18.8% and 63.8%, and the 5-year recurrence-free survival was 93.8%, 80.7% and 26.7% in low, intermediate and high-risk groups, respectively. (P < 0.001) Each increase in VENUSS score had 1.52-fold (95%CI:1.45-1.60, P < 0.001) DR risk. Compared with the VENUSS low risk, the intermediate risk had a 2.91-fold increased DR risk (95%CI:1.90-4.46, P < 0.001) and 17.9-fold (95%CI:12.25-26.25, P < 0.001) in high risk, while it was 6.07-fold greater in high risk vs. intermediate risk (95%CI:4.17-8.83, P < 0.001). The discrimination was 81.2% (95%CI:77.5%-84.8%) for the VENUSS score, and 78.6% (95%CI:74.8%-82.4%) for VENUSS risk groups, respectively. Both the VENUSS score and groups were well calibrated. This contemporary multi-institutional European large dataset validated the use of VENUSS score and VENUSS risk groups on the prediction of DR after curative surgery in patients with non-metastatic papRCC. The VENUSS prognostic model can provide valuable information for patient counselling, follow-up and patient selection for adjuvant trials.

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