Predicting Oncologic Outcomes in Small Renal Tumors

Background: Most patients diagnosed with renal cancer today present with small renal masses (SRMs). Although these patients have a low risk of dying from their disease and many are followed with active surveillance protocols, a small subset of renal cell carcinomas (RCCs) behave aggressively. Knowledge regarding features of aggressive behavior would enable better adoption of active surveillance strategies among these patients. Objective: We sought to improve prognostic models to predict metastasis-free survival after nephrectomy through focused analyses of clinicopathologic characteristics of SRMs associated with adverse outcomes. Design, setting, and participants: We identified consecutive patients with surgically resected SRMs (<4 cm) at the University of Texas Southwestern Kidney Cancer Program between 1998 and 2020. In addition, we evaluated the ability of SRMs to form tumors when implanted in mice, an indicator of tumor aggressiveness. Outcome measurements and statistical analysis: We examined the clinicopathologic factors associated with metastasis including prospectively performed BAP1 immunohistochemistry at our Clinical Laboratory Improvement Amendments laboratory. Multivariable Cox proportional hazard regression was used to predict metastasis-free survival. Results and limitations: A total of 3900 evaluable nephrectomies (from 3674 ethnically diverse patients) were identified, of which 1984 (51%) were SRMs including 1720 RCC. Of these patients with RCC (SRMRCC), 1576 did not have synchronous or metachronous larger RCCs and among these, 37 (2%) developed metastases. SRMRCC that metastasized were significantly enriched for aggressive morphologic phenotypes and engrafted in mice at comparable rates as larger metastatic tumors. BAP1 loss remained significantly associated with metastasis-free survival after accounting for TNM (tumor-node-metastasis) stage and SSIGN (stage, size, grade, and necrosis) score in multivariable analysis. Conclusions: We identified clinicopathologic features that influence metastasis-free survival for patients with SRMRCC. If validated independently, these data should assist with patient prognosis and help with active surveillance strategies.