High-grade clear cell renal cell carcinoma (ccRCC) is characterized by rapid progression and high recurrence risk, and the optimal surgical approach for such patients remains controversial. This study aims to compare the prognostic impact of partial nephrectomy (PN) and radical nephrectomy (RN) in such patients and provide evidence-based guidance for clinical decision-making.

This study was a multi-hospital retrospective cohort study. A total of 187 patients with high-grade (Fuhrman grade 3 to 4) ccRCC who underwent PN or RN at the urological departments of Daping Hospital, General Hospital of Central Theater Command, and Xiangyang First People’s Hospital between June 2010 and May 2023 were retrospectively enrolled. Meanwhile, 11580 patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (2010—2015) for external cohort validation. Patients were divided into the PN group and RN group according to the surgical approach, with overall survival (OS) as the primary endpoint. A 1 : 1 propensity score matching (PSM) was performed to balance the influence of baseline confounders. Kaplan-Meier analysis was used to plot survival curves and compare OS, and Cox proportional hazards regression analysis was employed to identify independent prognostic factors.

In the multi-hospital retrospective cohort, 36 patients underwent PN and 151 underwent RN before PSM. The PN group exhibited significantly smaller tumors (4.00 vs 6.00 cm, P<0.0001) and lower T stage (P<0.0001). Kaplan-Meier analysis showed that the PN group had a survival benefit compared with the RN group (P=0.046), but neither group obtained the median survival. After PSM (34 patients in each group), there were no significant differences between the 2 groups in terms of age, preoperative creatinine, sex, smoking history, diabetes, hypertension, N stage, tumor size, or tumor laterality (all P>0.05); Kaplan-Meier analysis showed no statistical difference in OS between the 2 groups (P=0.26), with the median survival not reached in either group. In the SEER cohort, the patients from the RN group were older and had greater tumor burden before PSM (both P<0.0001). After PSM (2807 pairs), baseline characteristics were well balanced; Kaplan-Meier analysis showed that significantly longer OS was observed in the PN group than the RN group (P<0.0001), but the median survival was still not reached in either group. Multivariable Cox regression analysis indicated that PN was an independent protective factor, whereas RN was an independent risk factor. RN was associated with a 33% increase in mortality risk compared with PN (HR=1.33, 95%CI: 1.21 to 1.46, P<0.001).

Based on the results of our multi-hospital retrospective cohort and the large-sample SEER database cohort analysis, for patients with high-grade ccRCC, PN demonstrates an OS benefit compared with RN, suggesting the potential value of PN and supporting the possible adoption of PN under strict adherence to surgical indications.