The current study is the natural extension of that work. We asked: What does that upstaging mean for patients? Specifically, how does survival differ when two patients both end up with pT3a disease, but one was clinically staged as cT3a while the other was upstaged from cT2? Surprisingly, we found that patients who were upstaged had significantly worse overall survival than those with concordant cT3a disease.
These results left us puzzled. How could two groups of tumors, ultimately assigned the same pathologic stage, behave differently in terms of survival? We explored all the obvious possibilities – differences in tumor size, histology, grade, necrosis, sarcomatoid features – and even after adjusting for these, the survival gap persisted. While we cannot say definitively why, one possibility is that upstaging reflects some underlying, more insidious biology not fully captured by current TNM staging or histopathologic metrics.
These findings have important consequences. For clinical trial design, excluding cT2 tumors from neoadjuvant or perioperative systemic therapy studies risks omitting a high-risk subgroup, given the high possibility of upstaging. For clinicians, it highlights the need to consider that a cT2 tumor – especially when ultimately upstaged – may carry a risk profile worse than its pathology alone suggests.
In short, this project began with a clinician’s curiosity, evolved into a question of concordance, and ultimately uncovered a provocative and somewhat unsettling survival signal. The story is far from over, but we hope these findings spark further investigation into the biological and clinical meaning of upstaging in kidney cancer.
Written by:
- Eric A. Singer, MD, Division of Urologic Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH
- Taylor Goodstein, MD, Fellow, Urologic Oncology, Department of Urology, Emory University Hospital, Atlanta, GA
- Goodstein T, Goradia RR, Srivastava A, et al. Concordance between clinical and pathologic staging of T2a–b and T3a renal cell carcinoma. J Clin Oncol. 2025;43(5_suppl):600-600. doi:10.1200/JCO.2025.43.5_suppl.600