Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database

Abstract

Objective: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC.

Methods: The INMARC database was queried for T1aN0M0 RCC. Patients were stratified into groups based on recurrence. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed for factors associated with recurrence, cancer-specific (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) assessed survival by histology and grade. Subset analysis for time to recurrence was conducted for grade and histologic groups and compared with recent AUA follow-up guidelines [low-risk (AUA-LR), intermediate-risk (AUA-IR), high-risk (AUA-HR), and very-high risk (AUA-VHR) groups].

Results: We analyzed 1,878 patients (median follow-up 35.2 months); 101 (5.4%) developed recurrence. MVA for recurrence demonstrated increasing age (P = 0.026), male sex (P = 0.043), diabetes (P = 0.007), high/unclassified grade (P < 0.001-0.007), and variant histology (P = 0.017) as independent risk factors for increased risk, while papillary (P = 0.016) and chromophobe (P = 0.049) were associated with decreased risk. MVA identified high/unclassified grade (P = 0.003-0.004) and pT3a upstaging (P = 0.043) as predictive factors for worsened risk of CSM while papillary (P = 0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (P = 0.022), variant histology (P = 0.049), recurrence (P = 0.004), and eGFR<45 at last follow-up (P < 0.001) to be independent risk factors. KMA comparing clear cell, chromophobe, papillary, and variant RCC revealed significant differences for 5-year CSS (P = 0.018) and RFS (P < 0.001), but not OS (P = 0.34). Median time to recurrence was 23.8 months for low-grade (AUA-LR), 17.3 months for high-grade (AUA-IR), 18 months for pT3a upstaging (AUA-HR), and 12 months for variant histology (AUA-VHR; P < 0.001).

Conclusion: 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. Our findings support recently promulgated AUA follow-up guidelines for low-grade and variant histology pT1a RCC, but call for consolidation of follow-up protocols for high-grade pT1a and pT3a upstaged patients, with intensification of frequency of imaging follow-up in pT1a high-grade RCC.

Keywords: Carcinoma, Renal cell; Nephrectomy; Recurrence; Survival; Tumor grading; Tumor histology.