Clinical implications of tumor laterality in renal cell carcinoma

It is unclear whether laterality has prognostic implications for patients with renal cell carcinoma (RCC). Some suggest that left sided tumors may have worse survival outcomes. The purpose of this study is to associate tumor characteristics and clinical outcomes with laterality in patients with RCC.

Patients with RCC were identified in the National Cancer Database between 2004-2020. Patients were categorized as having either localized, regional or metastatic disease. Time-series charts were generated to demonstrate laterality differences and variance over time. Multivariable Cox proportional hazards regression was utilized to associate laterality with overall survival, stratified by clinical stage. Kaplan-Meier estimates were utilized to visualize survival functions.

A total of 306,196 patients were included, 156,450 (51.1%) had right sided tumors and 283,282 (92.5%) had localized RCC. Localized tumors were more likely to be right sided (0.51 [95% CI 0.50-0.52], p < 0.001). Metastatic and regional tumors (cN+M0) were more likely to be left sided (0.48 [0.47-0.49], p < 0.001; and 0.43 [0.41-0.45], p < 0.001; respectively). For localized disease, smaller tumors were more likely to be right sided (< 2 cm: 0.52 [0.51-0.52], p < 0.001), while tumors > 7cm showed no significant site association (0.49 [0.49-0.50], p = 0.07). When stratified by staging, there were no significant associations between laterality and OS (localized RCC: HR 1.01 [0.99-1.02], p = 0.50; metastatic RCC: 1.03 [1.00-1.07], p = 0.7; cN+M0 RCC: 0.96 [0.86-1.07], p = 0.50).

Left-sided RCC tumors are associated with larger tumor size and a higher propensity for regional nodal involvement and distant metastases. However, they do not demonstrate more aggressive behavior leading to meaningful survival differences.