Evaluation of the prognostic significance of perirenal Fat invasion and tumor size in patients with pT1-pT3a localized renal cell carcinoma in a comprehensive multicenter study of the CORONA project : can we Improve prognostic discrimination for patients with stage pT3a tumors?

Background: The current TNM system for renal cell carcinoma (RCC) merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. In addition, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. Objective: To analyze the prognostic significance of PFI, RVI, and tumor size in pT1-pT3a RCC. Design, setting, and participants: Data for 7384 pT1a-pT3a RCC patients were pooled from 12 centers. Patients were grouped according to stages and PFI/RVI presence as follows: pT1-2N0M0 (n = 6137; 83.1%), pT3aN0M0 + PFI (n = 1036; 14%), and pT3aN0M0 (RVI ± PFI; n = 211; 2.9%). Intervention: Radical nephrectomy or nephron-sparing surgery (NSS) (1992-2010). Outcome measurements and statistical analysis: Cancer-specific survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional-hazards regression models, as well as sensitivity and discrimination analyses, were used to evaluate the impact of clinicopathologic parameters on cancer-specific mortality (CSM). Results and limitations: Compared to stage pT1-2, patients with stage pT3a RCC were significantly more often male (59.4% vs 53.1%) and older (64.9 vs 62.1 yr), more often had clear cell RCC (85.2% vs 77.7%), Fuhrman grade 3-4 (29.4% vs 13.4%), and tumor size >7. cm (39.1% vs 13%), and underwent NSS less often (7.5% vs 36.6%; all p <. 0.001). According to multivariate analysis, CSM was significantly higher for the PFI and RVI ± PFI groups compared to pT1-2 patients (hazard ratio [HR] 1.94 and 2.12, respectively; p <. 0.001), whereas patients with PFI only and RVI ± PFI did not differ (HR 1.17; p = 0.316). Tumor size instead enhanced CSM by 7% per cm in stage pT3a (HR 1.07; p <. 0.001) with a 7. cm cutoff yielding the highest prediction accuracy. Conclusions: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a RCC might be justified. Enhanced prognostic discrimination of stage pT3a RCC appears to be possible by applying a tumor size cutoff of 7. cm within an alternative staging system. Patient summary: Prognosis prediction for patients with localized renal cell carcinoma up to stage pT3a can be enhanced by including tumor size with a cutoff of 7. cm as an additional parameter in the TNM classification system. The prognostic impact of perirenal fat and renal vein invasion in renal cell carcinoma patients is comparable, which justifies merger of both as stage pT3a. Prognostic discrimination of pT3a tumors can be enhanced by using a tumor size cutoff of 7. cm for additional stratification.