Introduction:

In the literature, it is well established that 5–23% of patients with cT1 and smaller cT2 tumors may be upstaged to pT3a disease after surgery. The restaging rate of larger or clinically more invasive tumors, however, remains understudied. Recently, the PROSPER RCC clinical trial demonstrated no benefit in recurrence-free survival with perioperative nivolumab in patients with clinical stage T2 or greater, T_anyN+, or select M+ RCC. The authors acknowledged the inherent limitations of trial enrollment based on clinical factors, which includes the possibility of pathologic restaging after surgery. Understanding the frequency of pathologic restaging for larger tumors has key implications for future trials, as discordance between clinical and pathological stage can increase heterogeneity and may contribute to underpowered or negative studies. We aimed to determine the rate of restaging for cT2a-b and cT3a RCC after extirpative surgery. Based on historical reports, we hypothesized that up to 25% of patients with cT2 tumors would be pathologically restaged (i.e., have discordant clinical and pathologic staging).   

Methods:

Adult patients with American Joint Committee on Cancer (AJCC) clinical stage T2a, T2b, and T3a RCC undergoing partial or radical nephrectomy were identified using the National Cancer Database (NCDB). Baseline demographic data was collected, and final pathological T stage was recorded. Restaging rates were determined for the overall cohort and then stratified based on histology, nodal status, and metastatic disease status. Significance was defined as p < 0.05 and calculated using Chi square. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the overall cohort.

Results:

A total of 31,912 patients met inclusion criteria (13,840 cT2a, 8,079 cT2b, and 9,993 cT3a). The overall rate of restaging was 47.4% for cT2a disease (10.7% downstaged and 36.7% upstaged) for a sensitivity and specificity of 89% and 72%, respectively. The overall rate of restaging was 52.5% for cT2b disease (10.6% downstaged and 41.9% upstaged), for a sensitivity and specificity of 85% and 96%, respectively. The overall rate of restaging was 9.5% for cT3a disease (5.1% downstaged and 4.4% upstaged), for a sensitivity and specificity of 55% and 94%, respectively (p < 0.001). The positive predictive value was 52.5%, 47.5%, and 90.6%, and the negative predictive value was 95%, 97%, and 67% for cT2a, cT2b, and cT3a disease, respectively. The presence of clinically node-positive or metastatic disease significantly increased the likelihood of pathological upstaging of the primary tumor (p < 0.001). Non-clear cell histology (40% papillary, 30% chromophobe, 9% sarcomatoid, and 21% other) was associated with increased accuracy of clinical staging (p < 0.001).

Conclusion:

Of patients with cT2a and cT2b tumors, nearly half undergo pathologic stage change after surgery, with more than 20% downstaged. The specificity of cT3a staging is high, which suggests that clinical characteristics that are concerning for invasive disease are generally accurate. Additional work is needed to improve the accuracy of RCC clinical staging given the continued interest in perioperative systemic therapy trials.

Funding: N/A