Stage 3 renal cell carcinoma (RCC) comprises lymph node-positive and -negative disease, but new research suggests that lymph node-positive stage 3 disease is associated with worse survival, with a 5-year survival rate similar to that of patients with stage 4 RCC.

Findings support reclassification of stage 3 pN1 RCC as stage 4 disease, according to investigators.

Using 2004 to 2015 data from the National Cancer Data Base (NCDB), investigators identified and compared 2218 patients with American Joint Committee on Cancer (AJCC) lymph node-positive stage 3 disease (pT1-3N1M0), 6587 patients with lymph node-negative stage 3 disease (pT3N0M0), and 183 patients with metastatic stage 4 disease (pT1-3N0M1).

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The highest 5-year overall survival rate was found among patients with lymph node-negative stage 3 RCC: 61.9%. Lymph node-positive stage 3 patients had a worse 5-year overall survival rate, and this rate was similar to those with metastatic stage 4 RCC: 22.7% vs 15.6%, respectively, Eric A. Singer, MD, MA, MS, of Rutgers Cancer Institute of New Jersey in New Brunswick, and colleagues reported in Cancer.

Survival trends by histology were consistent. Among patients with clear cell RCC, the 5-year overall survival rates were 64.4% vs 28.7% vs 24.6%, respectively. Among patients with non-clear cell RCC, the corresponding rates were 53.1% vs 17.4% vs 5.2%, respectively. Expanding the comparator to all stage 4 cases (ie, adding pT4,N0-1,M0) did not alter the trend.

Having stage 3 disease, lymph node involvement, high-grade tumor histology, non-clear cell histology, and receipt of systemic therapy were all associated with worse survival.

“Current AJCC staging in patients with kidney cancer considers clinically localized, LN+ (pT1-3N1M0) RCC to be stage III disease,” Dr Singer’s team concluded. “However, we found that outcomes among these patients are clearly inferior to those of patients with LN- stage III RCC (pT3N0M0). Instead, these outcomes more closely follow the survival of patients with stage IV disease. We have validated prior institutional studies and built upon them using a large sample size and adjusting for systemic therapy. Consequently, the results of the current study also support the reclassification of stage III, pN1 RCC as stage IV disease.”


Srivastava A, Rivera-Núñez Z, Kim S, et al. Impact of pathologic lymph node–positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer. Cancer. 2020:126:2991-3001. doi: 10.1002/cncr.32912