Multi-Institutional Survival Analysis of Incidental Pathologic T3a Upstaging in Clinical T1 Renal Cell Carcinoma Following Partial Nephrectomy - Beyond the Abstract

Over the past two decades, there has been a dramatic shift in the identification and management of small renal masses. Historically, the vast majority of renal cell carcinomas (RCC) were symptomatic at presentation, typically indicative of disease requiring radical intervention for cure or disease control. This paradigm has rapidly changed with the widespread utilization of cross-sectional imaging, which has resulted in the increased detection of incidental small renal masses < 4 cm. While small renal masses were previously a rare entity, they now represent the most common RCC presentation. As the rate of small renal mass detection has increased, so too has the utilization of nephron-sparing approaches (partial nephrectomy, ablation, and stereotactic radiation) for the management of these lesions.

Imaging advances have allowed for the earlier detection of RCC, however, there has been minimal change in RCC mortality with almost 14,000 deaths reported each year. It is well documented that the majority of these deaths occur in patients with advanced stage, high grade, or metastatic disease at presentation. Renal sinus fat invasion, perinephric fat invasion, and early venous extension represent high-risk features corresponding to pathologic T3a (pT3a) disease in lesions that would otherwise be characterized as T1 by size criteria alone. Current imaging technologies are limited in their ability to accurately detect these characteristics resulting in a cohort of patients who undergo partial nephrectomy for clinical T1 (cT1) lesions who are subsequently upstaged to pT3a disease.

Radical nephrectomy represents the treatment of choice for patients with T3 disease, and thus incidental upstaging following partial nephrectomy results in the potential under-treatment of biologically aggressive disease. The natural history and expected survival outcomes of those with incidental pT3a upstaging, however, remains unclear. In order to address this question, we designed a multi-institutional study to compare outcomes of patients with incidental pT3a upstaging following partial nephrectomy to those with final pT1a/b disease.

In our study, patients with incidental pT3a upstaging after partial nephrectomy were individually matched by demographic (age and ECOG classification) and pathologic (tumor histology and Fuhrman grade) characteristics to patients who underwent partial nephrectomy with final pT1a/b disease. The primary endpoint of our study was recurrence-free survival (RFS), while cancer-specific survival (CSS), overall survival (OS), and rates of local and distant recurrence were evaluated as secondary endpoints.

This analysis revealed an inferior RFS (p=0.01), CSS (p<0.01), and OS (p=0.04) in the pT3a population. Those with incidental pT3a upstaging also demonstrated significantly higher rates of disease recurrence (20% vs. 9%), the vast majority of which were distant metastasis (85%). On further analysis of the pT3a population, there were no significant predictors of disease recurrence identified.

Given the fact that most recurrences in the pT3a population occur distantly, partial nephrectomy may still be appropriate surgical intervention especially if there is a need to preserve renal function.  Based on our findings, these patients could be considered for adjuvant therapy to reduce the risk of recurrence as supported by the S-TRAC trial.1  Additionally, this represents an important population that may benefit from enrollment in current trials utilizing adjuvant immunotherapy such as KEYNOTE-564.  Regardless of adjuvant therapy, it is clear that these patients need to undergo more frequent and intensive surveillance than their T1a counterparts.  While we have not had a significant impact on survival for high-risk renal cell carcinoma to date, earlier identification and more aggressive adjuvant therapy likely represent our greatest opportunity.  

Written by:
Christopher Russell, MD, Urology House Officer, PGY-3, Department of Urology, University of Michigan, Ann Arbor, Michigan
Alon Weizer, MD, Associate Professor, Urology, Associate Chair, Surgical Services, Department of Urology, University of Michigan, Ann Arbor, Michigan

References:

  1. Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. N Engl J Med. 2016;375:2246-2254.
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