Study of the Kidney Tumor-Parenchymal Interface after Neoadjuvant Treatment with Axitinib for Locally Advanced Clear Cell Renal Cell Carcinoma: Matched Analysis from a Phase II Trial

Purpose The aim of this study was to evaluate histological changes in the tumor-parenchymal interface in clear cell renal cell carcinoma after neoadjuvant axitinib treatment. Materials and Methods We obtained clinical and pathology materials from 23 patients with clear cell renal cell carcinoma treated with neoadjuvant axitinib in a phase II clinical trial and from 23 matched patients with clear cell renal cell carcinoma who underwent upfront surgery. Histology of the tumor pseudocapsule and the peritumor kidney parenchymal change was evaluated and compared between the 2 cohorts. Results A tumor pseudocapsule was noted in all 23 patients who received neoadjuvant axitinib and in all 23 control patients. Most pseudocapsules were noncontinuous and only partially covered the tumor, including in 17 of 23 axitinib cases (74%) and 19 of 23 controls (83%). In axitinib cases the median thickness of the intrarenal and extrarenal pseudocapsule was 1.4 and 2.4 mm, respectively, which was significantly thicker than in control cases (intrarenal p = 0.0008 and extrarenal p <0.0001). The thickness of the pseudocapsule in axitinib treated cases was more frequently irregular compared to that in controls (16 of 23 or 70% and 9 of 23 or 39%, respectively, p = 0.0746). Inflammation, nephrosclerosis, glomerulosclerosis and arteriosclerosis decreased with increasing distance from the tumor edge in the neoadjuvant axitinib and control groups. Conclusions The tumor pseudocapsule becomes irregularly thick after neoadjuvant axitinib therapy. Although axitinib likely evokes a strong fibrous reaction in the tumor-parenchymal interface, it does not affect the frequency of infiltrative tumor invasion to the outside of the pseudocapsule or the degree of atrophic/inflammatory change in tissue surrounding the tumor. These findings support the notion that partial nephrectomy could be safely done in well selected patients after neoadjuvant axitinib.