Patterns of Initial Metastatic Recurrence After Surgery for High-Risk Nonmetastatic Renal Cell Carcinoma

Objective: To evaluate postoperative recurrence patterns for high-risk nonmetastatic renal cell carcinoma (RCC) and to identify prognostic factors associated with site-specific metastatic recurrence using a multi-institutional contemporary cohort. Methods: Data for nonmetastatic ≥pT3a RCC patients treated with surgery at 4 independent centers was analyzed. Initial recurrence locations were identified, and imaging templates were defined by anatomic landmarks using radiologic definitions. Prognostic factors for site specific recurrence were evaluated with univariate and multivariable analyses. Results: A total of 1057 patients were treated surgically for ≥pT3a RCC. Initial recurrence location was in a single site for 160 (59.3%) patients and at multiple locations in 110 (41.7%) patients. The most common sites of metastatic recurrence were lung (144/270, 53.3%), liver (54/270, 20.0%), and bone (48/270, 17.8%). Recurrence was identified in 52 of 270 (19.3%) patients outside the chest/abdomen template, most commonly in the pelvis (25/270, 9.3%). Bone and brain metastases were the most common organs for metastases outside chest/abdomen. Patients with tumor diameter >10 cm and grade 4 were more likely to recur in the bone (HR 3.61, P <.001) and brain (HR 16.5, P <.001). Conclusion: Metastatic progression outside chest/abdomen imaging templates was present in 1 of 5 high risk patients at initial metastatic RCC diagnosis, most commonly in the pelvis. Patients with large (>10 cm) tumors and grade 4 histology are at highest risk for bone and brain metastases.