Reassessment of American Joint Committee on Cancer Staging for Stage III Renal Cell Carcinoma With Nodal Involvement: Propensity Score Matched Analyses of a Large Population-Based Study

Background: To assess the role of nodal involvement in stage III renal cell carcinoma (RCC) according to the American Joint Committee on Cancer (AJCC) 8th staging system. We compared the survival outcomes of RCC patients with pT_1-3N₁M₀ disease and those with pT₃N₀M₀ or stage IV (stratified as pT₄N_anyM₀ and pT_anyN_anyM₁) disease in a large population-based cohort. Methods: A cohort of 3,112 eligible patients with RCC was identified from the Surveillance, Epidemiology, and End Results (SEER) database, registered between January 2004 and December 2015. Kaplan-Meier and Cox proportional hazards models were used to evaluate the overall survival (OS), and cancer-specific survival (CSS). The prognostic value of the modified stage for pT_1-3N₁M₀ disease was assessed by nomogram-based analyses. Propensity score matching (PSM) was used to adjust for potential baseline confounding. Results: Patients with pT_1-3N₁M₀ disease showed similar survival outcomes (median OS 41.0 vs. 38.0 months, P = 0.77; CSS 45.0 vs. 39.0 months, P = 0.59) to pT₄N_anyM₀ patients, whereas the significantly better survival outcome was found for pT₃N₀M₀ patients. After PSM, comparable survival rates were observed between pT_1-3N₁M₀ group and pT₄N_anyM₀ group, which were still significantly worse than the survival of pT₃N₀M₀ patients. The modified stage IIIA (pT₃N₀M₀), IIIB (pT_1-3N₁M₀, pT₄N_anyM₀), and IV (pT_anyN_anyM₁) showed higher predictive accuracy than AJCC stage system in the nomogram-based analyses (concordance index: 0.70 vs. 0.68, P < 0.001 for OS; 0.71 vs. 0.69, P < 0.001 for CSS). Conclusions: The pT_1-3N₁M₀ RCC might be reclassified as stage IIIB together with pT₄N_anyM₀ disease for better prediction of prognosis, further examination and validation are warranted.