Analysis of factors affecting the upstaging and downstaging of renal cell carcinoma from T1 to T3a and the impact of different surgical approaches on patient prognosis and survival: a multicenter retrospective study

Background: Discrepancies between clinical and pathological staging in renal cell carcinoma (RCC) can affect surgical choices and prognosis. While predictors of upstaging from cT1 to pT3a have been explored, downstaging of cT3a to pT1 has rarely been reported. This study aimed to quantify the incidence and determinants of upstaging (cT1→pT3a) and downstaging (cT3a→pT1) and to evaluate their associations with progression-free survival (PFS) and overall survival (OS). Methods: We conducted a retrospective multicenter cohort study across four tertiary hospitals in China. Consecutive adults undergoing partial or radical nephrectomy (RN) between January 2013 and January 2023 were included. The primary outcomes were upstaging (cT1→pT3a) and downstaging (cT3a→pT1), and the secondary outcomes were OS and PFS. Determinants were evaluated using multivariable logistic regression, and survival was estimated by Kaplan-Meier analysis with log-rank tests; two-sided P<0.05 indicated statistical significance. Results: Among 2,015 patients, 137 (6.8%) were upstaged (cT1→pT3a), and 24 (1.2%) were downstaged (cT3a→pT1). Upstaging was independently associated with larger tumor diameter [per 10 mm increase: odds ratio (OR) =1.93], irregular tumor morphology (OR =1.72), higher Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score (OR =1.63), central location (vs. intermediate: OR =0.57; vs. peripheral: OR =0.55 for not central), and higher International Society of Urological Pathology (ISUP) grade (OR =4.49). Downstaging was associated with smaller tumor diameter (per 10 mm decrease: OR =0.93), higher PADUA score (OR =2.48), and central location (vs. intermediate: OR =0.18; vs. peripheral: OR =0.21 for not-central). The median OS was 76.1 months in the upstaged group, 106.3 months in the T1 group (cT1→pT1), 104.7 months in the downstaged group, and 85.0 months in the T3a group (cT3a→pT3a); the median PFS was 45.1, 97.4, 100.4, and 80.6 months, respectively. The OS and PFS of upstaged patients were significantly inferior to those of patients with T1, downstaged, and T3a disease (all P<0.05). Conclusions: Stage discordance between cT1 and pT3a is uncommon but clinically meaningful. A “size-morphology-location-complexity-grade” phenotype identifies patients at risk of upstaging and worse survival, supporting intensified imaging review and intraoperative frozen section might be considered. A lower threshold for conversion from partial to RN warrants future prospective investigation when oncologic safety is uncertain. Conversely, some cT3a lesions—especially small, centrally located, high-complexity masses—may be suitable for nephron sparing surgery with meticulous margin control.