The increase in cancer-specific mortality (CSM) associated with pathologically confirmed adjacent organ invasion (pT4) in non-metastatic (M0) renal cell carcinoma (RCC), relative to limited local invasion (pT3) or no local invasion (pT2) with otherwise same patient and tumor characteristics, is unknown. We addressed this knowledge gap.
Within the Surveillance, Epidemiology, and End Results database (2004-2022), M0 RCC patients treated with radical nephrectomy were identified. Propensity score matching (PSM) was applied, and multivariable competing-risks regression (CRR) models were fitted. Additional sensitivity analyses were performed to evaluate the robustness of the primary findings.
Of 27,859 patients, 666 (2.4%) were classified as pT4, 15,343 (55.1%) as pT3, and 11,850 (42.5%) as pT2. After PSM, CSM at 120 months was 63.0% in pT4 versus 43.2% in pT3 and 26.0% in pT2. In multivariable CRR models, pT4 was associated with 1.84-fold higher CSM compared with pT3 (p < 0.001) and 3.31-fold higher CSM compared with pT2 (p < 0.001). In sensitivity analyses restricted to patients with clear-cell RCC, patients diagnosed before approval of adjuvant systemic therapy, and patients without lymph node invasion, corresponding effect estimates ranged from 1.79 to 1.93 for the comparison with pT3 and from 2.96 to 3.47 for the comparison with pT2 (all p < 0.001).
In M0 RCC, the presence of adjacent organ invasion (pT4) doubles the rate of CSM relative to pT3 and triples the rate of CSM relative to pT2 when all other tumor and patient characteristics are held constant. These findings quantify the very aggressive nature of pT4 independent of other tumor and patient characteristics and thereby validate contemporary T staging. Accordingly, more frequent follow-up and prioritization of pT4 patients for discussions regarding adjuvant systemic therapy may be warranted compared with their pT3 and pT2 counterparts.
World journal of surgical oncology. 2026 Jul 20*** epublish ***
Maximilian Filzmayer, Leonardo Quarta, Michele Petix, Filippo Orlandi, Jordan A Goyal, Alberto Briganti, Luca Carmignani, Salvatore Micali, Shahrokh F Shariat, Matthias J Müller, Clara Humke, Miriam I Traumann, Fred Saad, Felix K-H Chun, Pierre I Karakiewicz
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Canada. ., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Canada., Vita-Salute San Raffaele University, Milan, Italy., Università degli Studi di Milano, Milan, Italy., Department of Urology, AOU di Modena, University of Modena and Reggio Emilia, Modena, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.