416 Background: The renal cell carcinoma (RCC) TNM system merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. Additionally, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. Methods: Data of 7,595 pT1a-pT3a RCC patients undergoing radical nephrectomy or nephron-sparin surgery were pooled from 12 European and U.S. centers (1999-2010). Patients were grouped according to stages and presence of PFI/RVI, i.e., pT1-2N0M0 (n=6,137; 80.8%), pT3aN0M0+PFI (n=1,036; 13.6%), and pT3aN0M0 (RVI±PFI; n=422; 5.6%). Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Univariate and multivariable Cox proportional-hazards regression models, sensitivity and discrimination analyses were conducted to evaluate the impact of clinico-pathological parameters on cancer-specific mortality (CSM). Results: Compared to stage pT1-2, patients staged pT3a were significantly more frequently male (58.9 vs. 53.1%), older (65 vs. 62.1 yrs), more often had clear cell RCC (86.1 vs. 77.7%), Fuhrman grade 3-4 (30.5 vs. 13.4%), tumor size >7 cm (39.6% vs. 13%), and less often underwent NSS (7.1 vs. 36.6%; each p<0.001). On multivariable analysis, CSM of both patients with PFI and RVI±PFI was significantly enhanced compared to pT1-2 patients (HR 1.96 and 2.14, resp.; p<0.001), whereas patients featuring PFI only and RVI±PFI did not differ (HR 0.92; p=0.48). Tumor size instead significantly influenced CSM in stage pT3a (HR 1.07; p<0.001) with a 7 cm cut-off yielding the highest c-index. Conclusions: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a might be justified. Enhanced prognostic discrimination of stage pT3a RCC patients appears to be possible by employing a 7 cm tumor size cut-off within an alternative staging system.
