Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.
Authors: Liu Franklin , Wang Luke , Dhanji Sohail , Meagher Margaret F , Ghassemzadeh Saeed , Shah Aastha , Puri Dhruv , Nguyen Mimi , Hakimi Kevin , Cerrato Clara , Afari Jonathan , Patil Dattatraya H , Tanaka Hajime , Saito Kazutaka , Fujii Yasuhisa , Master Viraj A. , Derweesh Ithaar 
Published: March 2023

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Background: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnoses at earlier clinical tumor stage and has rendered the phenomenon of the ‘small renal mass’ as a dominant presenting clinical paradigm. While thought of as being low risk, emerging knowledge about heterogeneity of RCC histologies and consequent impact on prognosis, in addition to awareness of impact of functional decline and demographic drivers on outcomes led us to further explore outcomes and predictive factors in T1a RCC patients treated with surgical resection. Methods: The INMARC database was queried for patients with small renal masses (≤ 4 cm) who underwent surgery via partial or radical nephrectomy and who presented without nodal or distant metastases. Patients were stratified into two groups based on having recurrence (distant or loco-regional) or not. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed to analyze clinicopathological variables associated with recurrence and identify predictors of recurrence, cancer-specific mortality (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) were performed to compare recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) between histology types clear cell, chromophobe, papillary, and “other.” Results: We analyzed 1,878 cT1aN0M0 RCC patients; 101 (5.4%) developed recurrence (median follow up 53.6 months; median time to recurrence 19.3 months); 51.1% developed distant recurrence, 35.6% had loco-regional recurrence, and 13.9% experienced distant and loco-regional recurrence. MVA demonstrated age (HR=1.02, p=0.02), sex (HR=1.71, p=0.045), diabetes (HR=1.94, p=0.006), high/unclassified grade (HR=2.82-4.40, p<0.001-0.007), papillary (HR=0.37, p=0.013) and other (HR=2.51, p=0.019) RCC as predictive factors for recurrence. MVA identified high/unclassified grade (HR=3.17-6.22, p=0.002-0.003) and papillary RCC (HR=0.12, p=0.036) as predictive factors for CSM. MVA for ACM demonstrated age (HR=1.03, p<0.001), non-Caucasian race (HR=0.85, p<0.001), high grade (HR=1.42, p=0.024), recurrence (HR=1.86, p=0.003), and GFR<45 (HR=2.89, p<0.001) to be independent risk factors. KMA comparing Clear Cell, Papillary, Chromophobe and Other RCC revealed significant differences for 5-year CSS (97.8% vs. 99.3% vs. 98.5% vs. 87.0%, p=0.018) and 5-year RFS (92.4% vs. 96.0% vs. 97.8% vs. 81.7%, p<0.001), but not 5-year OS (89.4% vs. 85.2% vs. 93.2% vs. 73.7%, p=0.34). Conclusions: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. These findings suggest consideration to refine management and post treatment surveillance strategies in T1a RCC.