Factors influencing the development of peritumoral capsule formation and prognostic impact of capsule penetration after minimal partial nephrectomy for clear cell RCC

Introduction & Objectives: To analyse peritumoral capsule thickness, searching for any correlation with the main pathological variables and to evaluate the prognostic impact of capsule penetration on local and systemic recurrence in patients treated by NSS for clear cell RCC with negative surgical margins. Materials & Methods: Between 2005 and 2007, 115 consecutive patients with single sporadic clear cell RCC had NSS performed as “minimal” partial nephrectomy. Peritumoral capsule status, its thickness, pericapsular tumor lymphocytic infiltration (TIL) and main pathological variables were carefully analyzed. Peritumoral capsule thickness was measured at the four corners of the sampling. Results: Mean peritumoral capsule thickness at the inner and at the outer poles of the tumor (SD, median, range) were 412 μm (250, 350, 20-1511) and 385 μm (253, 358, 20-1770), respectively. In 35 cases (21%) a TIL was present.Overall, in 68 (59.1%) cases the peritumoral capsule was intact and free from neoplastic penetration (PC-) while in 47 (40.2%) there were signs of penetration. Overall, 29.6% had capsular penetration on the parenchymal side (PCK). Whereas, 11.3% had peritumoral capsule invasion on the perirenal fat tissue side (PCF). At univariate analysis, thickness of tumor capsule did not significantly correlate with capsular involvement neither with main pathological variables nor with TIL. The capsule thickness measurements were significantly different among the four evaluated points in each single tumor, showing a decreasing thickness from the parenchimal pole to the perinephric pole (p<0.0008). Overall, at a mean (median, range) follow up of 44 months (46, 25-69), 5-year cancer-specific and progression–free survival were 91.7% and 89.5%. We stratified progression-free survival according to the side of capsular penetration (PCK vs. PCF) and compared the results to those of clear cell RCC with PC-. The 5-year progression-free survival for tumors PC-, PCK and PCF was 97%, 96.2% and 48.5% (p<0.0001; PC- vs. PCF p<0.0001; PCK vs. PCF p=0.0002). The multivariate model showed PCF to be the sole significant independent predictor of progression-free survival. Conclusions: The capsule thickness presents significant variations among the four evaluated anatomical corners in each single tumor, with a greater development in the inner pole, thus hypothesising a specific role of healthy parenchyma for its formation. PCF is a significant predictor of worse outcome and the sole independent prognostic factor at the multivariate analysis. Patients with clear cell RCC with PC-, as well as those with PCK, had an excellent prognosis and these pathological features could be possibly add to prognostic nomograms if proved statistically significant in larger series with longer follow-up.