The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery.

We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1-4, N0-1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups.

We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups.

We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.

BMC medicine. 2019 Oct 03*** epublish ***

Tobias Klatte, Kevin M Gallagher, Luca Afferi, Alessandro Volpe, Nils Kroeger, Silvia Ribback, Alan McNeill, Antony C P Riddick, James N Armitage, Tevita F ‘Aho, Tim Eisen, Kate Fife, Axel Bex, Allan J Pantuck, Grant D Stewart

Department of Urology, Addenbrooke’s Hospital, Cambridge, UK. ., Department of Urology, Western General Hospital, Edinburgh, UK., Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy., Department of Urology, Ernst-Moritz-Arndt-University, Greifswald, Germany., Institute of Pathology, Ernst-Moritz-Arndt-University, Greifswald, Germany., Department of Urology, Addenbrooke’s Hospital, Cambridge, UK., Department of Oncology, Addenbrooke’s Hospital, Cambridge, UK., Division of Surgical Oncology, Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Institute of Urologic Oncology, Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA.