T staging system for kidney cancer has undergone revisions, particularly focusing on defining and subclassifying T3 disease. Our prior study highlighted the prognostic impact of renal parenchymal infiltration or micronodular spread (RPI/MNS) in clear cell renal cell carcinoma (ccRCC) (Tanaka et al., Mod Pathol, 2024). This study assessed the prognostic performance of the current UICC 8th T staging system and explored the potential role of RPI/MNS in further refining the T3 classification.
We analyzed 324 patients with cN0M0 ccRCC who were managed with radical nephrectomy. Two pathologists analyzed whole tissue sections from nephrectomy specimens and determined pT stages according to the UICC 8th edition, WHO/ISUP grade, microvascular invasion, and RPI/MNS, where cancer cells infiltrated or spread into the renal parenchyma by involving normal renal tissue and/or by forming micronodules. The prognostic impacts of pathological factors were assessed using multivariable analysis for recurrence-free survival (RFS). C-indices were calculated for the UICC 8th T staging and for the T staging models that incorporate RPI/MNS.
Overall, 124/83/13/93/10/1 patients were diagnosed with pT1a/1b/2/3a/3b/4, respectively. The patients were grouped into pT1-2, T3a, and T3b-4 for further analysis. RPI/MNS was identified in 35 patients, including 14/14/7 patients in the pT1-2/3a/3b-4 groups, respectively. Recurrence occurred in 63 patients, and 9 died of RCC. Multivariable analysis showed that both pT stages and RPI/MNS were independently associated with RFS, with RPI/MNS showing a higher hazard ratio (5.51) than pT3a (1.99) and pT3b-4 (3.55). C-indices for RFS by the UICC 8th T staging and T staging models incorporating RPI/MNS as a pT3a factor or a pT3b factor were 0.69 (0.63-0.76), 0.76 (0.70-0.81), and 0.79 (0.73-0.84), respectively. The five-year RFS for pT1-2/3a/3b-4 stages were 90/69/24%, 94/65/24%, and 94/77/29% in the respective models. Analogous findings were observed for cancer-specific survival, showing C-indices of 0.76 (0.61-0.91), 0.81 (0.73-0.90), and 0.88 (0.80-0.97) for the respective models.
RPI/MNS exhibited a strong prognostic impact in non-metastatic ccRCC. Incorporating RPI/MNS into the current T staging could further refine T3 disease classification, potentially enhancing prognostic accuracy.
