Correlation Between Number of Positive Lymph Nodes and Prognostic Stratification in RCC

Renal cell carcinoma (RCC) with lymph node positivity is associated with poor oncologic outcomes for patients; however, the actual prognostic significance of node positivity is poorly understood. American Joint Committee on Cancer Stage III RCC currently includes both node-positive pN1 and node-negative pN0 disease.

A team of researchers recently hypothesized that (1) there is a threshold in the number of pathologically positive nodes that distinguishes favorable-risk from poor-risk nodal disease, and (2) current categorization of pN1 can be subdivided into pN1 and pN2 based on this threshold. The research team tested their hypothesis in a study using patient data taken from the National Cancer Database and shared the results at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Researchers used data on patients with RCC who were 18 years or older from 2004 to 2019. Patients with pathologic node-positive disease and without synchronous metastasis were chosen for analysis to minimize confounding from metastatic burden. Multivariable Cox proportional-hazards regression tested the association between the number of pathologically positive lymph nodes and all-cause mortality (ACM), adjusting for clinical and pathologic co-variables. Researchers used receiver operating characteristic (ROC) curve analyses using the concordance probability method to evaluate performance of potential cut points for pN2 node positivity. Kaplan-Meier analyses (KMA) were used to compare these thresholds against overall survival (OS) in patients with nonmetastatic Stage IV RCC.

A total of 28,590 patients who met the criteria were identified, and 13.6% of patients had pN1 disease. On multivariable analyses, increased pathologic node positivity was associated with an increased hazard of ACM (hazard ratio [HR], 1.19; 95% CI, 1.17-1.20; P<.001). ROC curve mapping of all lymph node thresholds from ≥2 to ≥10, with Stage IV as the highest point, had a comparable concordance probability among the cutoffs (0.26-0.33, area under the curve=0.656).

On KMA, when the threshold was set at ≥3, the 5-year OS was no longer significantly different from nonmetastatic Stage IV RCC, as seen in the overlapping confidence intervals. The research team designated pN1 as 1 to 2 pathologically positive nodes, and they designated pN2 as ≥3 pathologically positive nodes.

The 5-year OS was 69.4% (95% CI, 68.4-70.5) for Stage III pN0, 41.4% (95% CI, 39.0-43.8) for Stage III pN1, 31.8% (95% CI, 28.2-35.9) for Stage III pN2, and 30.0% (95% CI, 28.2-32.0) for nonmetastatic Stage IV. On multivariable analyses, pN2 had a 38% greater hazard of ACM (HR, 3.31; 95% CI, 2.24-2.54; P<.001) when compared with pN1 (HR, 2.39; 95% CI, 2.24-2.54; P<.001).

These research findings demonstrate the impact of positive nodal counts on prognostic stratification in RCC. Pathologic node positivity could be stratified to pN1 and pN2, with pN2 conferring poor prognostic risk comparable with nonmetastatic Stage IV pN0 disease. While further validation studies are needed, consideration should be given to stratifying Stage III pN2 patients to a higher risk group.