We previously published a predictive model to determine the preoperative risk of metastatic recurrence in localized renal cell carcinoma. We sought to validate this initial nomogram and interrogate the additive value of somatic mutations in a subcohort with available genomic data.

We conducted a retrospective review of all non metastatic patients at a single tertiary referral center from 2004–2011 who underwent a surgical extirpation for a renal mass (n=2391). Mutations in VHL, PBRM1, SETD2, BAP1, KDM5C for those patients who had genomic analysis by previously described MSK IMPACT were recorded. Nomogram for 12–year metastasis free survival published by Raj et al in 2008 was validated using Kaplan–Meier estimates. Associations between covariates and time to metastasis were calculated by Cox regression.

An initial cohort of 281 patients was available for analysis. Median age at time of surgery was 61.3 (24.7–84). Table 1 lists the clinical characteristics and associations to time to metastasis. There were 33 patients who developed metastatic disease on median follow–up of 9 years (Figure 1). Associations between the five preoperative characteristics and time to metastasis were similar to the original report. The linear predictor from the nomogram was highly associated with metastasis free survival (p<0.0001). We split the predicted 12–year metastasis free probability into quartiles, and used them to calculate the estimated 12–year survival in this cohort: it was not estimable in the first quartile, and 37.5%, 71% and 92% in 2nd, 3rd and 4th quartile, indicating good calibration of the original nomogram (Figure 2). KDM5C was significantly associated with metastasis–free survival and remained significant after incorporating nomogram prediction into the model (p=0.04, HR=3.6, 95% CI 1.05,12.4).

Univariate assessment of factors in our original model are associated with metastatic recurrence. Further statistical analysis of the complete cohort and integration of genomic data is ongoing.

Supported by the Sidney Kimmel Center for Prostate and Urologic Cancers, Ruth L. Kirschstein National Research Service Award T32CA082088 (MG& AS)