Introduction:

Administration of adjuvant immunotherapy for high-risk (T3) Renal Cell Carcinoma (RCC) has recently become a standard of care with publication of KEYNOTE-564 demonstrating survival benefit in this patient group. Presence of high tumor grade is increasingly understood as marker for adverse oncological outcomes in T1 and T2 RCC. We sought to compare survival outcomes of T1-T2 high-grade disease and T3 RCC.

Methods:

Prospectively collected data from a multicenter database involving University of California San Diego Health (USA), IRCCS San Raffaele Hospital (Italy), Emory University Hospital (USA) and Tokyo Medical and Dental University (Japan) were retrospectively analyzed, collecting a total of 5452 non metastatic patients treated with radical or partial nephrectomy. Baseline patient [age, sex, Body Mass Index (BMI), Charlson Comorbidity Index (CCI)] and tumoral characteristics (histology, RENAL score, tumor size, pathological N stage] were evaluated. Kaplan-Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS) in T1-T2 high-grade and T3 RCC. Cox regression was utilized to evaluate for predictors for CSM and ACM while controlling for demographic and pathological factors.

Results:

Median follow-up was 61 months. A total of 5007 patients with a T1-T2 High Grade (HG) tumor and 445 patients with a T3 any Grade tumor were analyzed. Kaplan-Meier analysis revealed that the 5-year CSS for T1-T2 high-grade tumors was 87%, while for T3 tumors it was 86%, indicating comparable survival rates between the two groups (p=0.08). 5-year OS was similar, being 78% for T1-T2 HG and 78% for T3 any Grade (p=0.11). Cox regression analyses showed that stage (T1-T2-HG vs T3a stage) was not predictive of differences in CSM (HR 1.24, p=0.15), or in ACM (HR 1.25, p=0.06).

Conclusion:

Cancer-specific mortality is comparable between T1-T2 high-grade tumors and T3 tumors while overall mortality is similar between T1-T2 HG and T3a any grade tumors. Hence, caution must be exercised when managing localized RCC with adverse pathological features, as its prognosis may be as severe as that of a locally advanced disease. Our findings suggest the need to reevaluate the inclusion criteria for adjuvant clinical therapy trials to consider T1-T2 high-grade renal cell carcinoma in future studies.

Funding: N/A