A comparison of radiographic and morphometric characteristics and outcomes in T3a pathologically upstaged and non-upstaged renal cell carcinoma.
Authors: Ghassemzadeh Saeed , Shah Aastha , Wang Luke , Liu Franklin , Dhanji Sohail , Hakimi Kevin , Nguyen Mimi , Puri Dhruv , Cerrato Clara , Nasseri Ryan , Meagher Margaret F , Javier-Desloges Juan , Derweesh Ithaar H 
Published: March 2023

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Background: A significant portion of patients presenting with clinically localized stage 1-2 renal cell carcinoma are pathologically upstaged to Stage 3 following surgical intervention. This is due to previously undetected extension into the renal venous system, perirenal or renal sinus fat, or collecting system. Improved detection of potential T3 upstaging may prompt changes in disease management, which may impact patient survival. We sought to compare pathologically upstaged and non-upstaged T3a RCC cases to identify characteristics of upstaged masses, predictors of T3a disease, and impact on oncological outcomes. Methods: We conducted a single center retrospective analysis of patients with pathologic T3a RCC who underwent surgical intervention. The cohort was divided into a group of patients with masses not preoperatively identified as cT3a (upstaged, cT1-cT2/pT3a) and a group of patients with masses preoperatively identified as cT3a (non-upstaged, cT3a/pT3a) for descriptive and outcomes analyses. We sought to delineate proportion of under-diagnosed pT3a RCC, location of upstaged disease, and predictors of upstaging. Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Multivariate analyses (MVA) were performed to identify predictors of T3a invasion site and outcomes. Kaplan Meier survival analyses (KMA) were performed to compare survival outcomes. Results: We analyzed 185 patients, of which 120 (64.9%) were upstaged and 65 (35.1%) were non-upstaged. When compared to non-upstaged masses, upstaged masses were significant for smaller size (6.8 vs 8.2 cm, p=0.008), lower RENAL score (8.7 vs 9.9, p<0.001), less hilar involvement (29.2% vs 86.2%, p<0.001), and increased exophyticity (41.7% vs 23.1%, p=0.011). On pathology, upstaged masses had greater proportions of perirenal fat invasion (53.3% vs 33.8%, p=0.011), but less venous system (44.2% vs 78.5%, p<0.001) and sinus fat invasion (35.8% vs 63.1%, p<0.001) compared to non-upstaged masses. RENAL domains R (OR=2.30-2.49, p=0.037-0.042), E (OR=0.39-2.32, p=0.003-0.009), and L (OR=0.53-7.70, p=0.001-0.031) were independent predictors for T3a disease foci. MVA demonstrated an association between non-upstaged status and recurrence (HR=2.01, p=0.043) but not overall mortality (HR=1.27, p=0.581). KMA noted better RFS in upstaged patients compared to non-upstaged patients (80.8% vs 75.4%, p=0.002), but no OS differences between upstaged and non-upstaged patients (74.2% vs 83.1%, p=0.209). Conclusions: Pathologically upstaged T3a RCC is associated with distinct morphology and invasion patterns and higher recurrence-free survival outcomes compared to non-upstaged T3a RCC. RENAL domains can assist in identifying masses with upstaging potential, predicting their invasion site, and performing preoperative risk stratification.