OBJECTIVE

To review the clinicopathological features of -rearranged renal cell carcinoma (-RCC) with venous tumor thrombus (VT) (-VT), to explore treatment strategies and to prognostic characteristics, and to provide diagnostic and therapeutic references for -VT patients.

METHODS

Patients who underwent surgery at Department of Urology, Peking University Third Hospital from January 2013 to January 2024 were enrolled, including three cohorts: Pathologically confirmed -VT patients, -RCC patients without VT (-non-VT), and non--rearranged renal cell carcinoma patients with VT (non--VT). Clinical history, imaging data, pathological data, and follow-up records were collected. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. (1) Baseline characteristics were compared between the -VT and -non-VT patients. Normally distributed continuous variables were expressed as mean±SD and compared using Student's -test; non-normally distributed variables were expressed as (, ) and analyzed with Mann-Whitney test; categorical variables were described as frequency and percentage [ (%)] and compared by test or Fisher's exact test. (2) Clinical history, radiological presentations, surgical data, and histopathological features of the -VT patients were comprehensively characterized. (3) Survival analysis was performed for the -VT patients. Follow-up data of the -VT patients were described in detail, and their survival outcomes were compared with the -non-VT and non--VT patients. When compared with the -non-VT counterparts, Kaplan-Meier method was used to generate PFS and OS curves among: (1) the -RCC patients across clinical stages Ⅰ-Ⅳ; (2) -VT -non-VT cohorts; (3) stage Ⅲ subgroups of the -VT and -non-VT patients. Intergroup survival differences were statistically evaluated using Log-rank tests. For comparisons with the non--VT patients, a 1 : 1 propensity score matching (PSM) was implemented to balance baseline characteristics between the two cohorts. Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups, with Log-rank tests employed to determine statistical significance of survival disparities. All statistical analyses were conducted with R software (v 4.2.3), and two-tailed < 0.05 was considered statistically significant.

RESULTS

The study included 45 -RCC patients: 13 -VT and 32 -non-VT cases. Additionally, 523 non--VT patients were enrolled. Among the 13 -VT patients, 9 were female (69.2%) and 4 male (30.8%), with a mean age of (37.9±14.4) years, mean BMI of (22.2 ± 3.5) kg/m, median age-adjusted Charlson comorbidity index (aCCI) of 1.0 (0.0, 1.0), and preoperative creatinine level of (75.3±15.9) μmol/L; tumors were located in the left kidney in 7 patients (53.8%) and right kidney in 6 (46.2%); preoperative distant metastasis (M1 stage) was present in 6 patients (46.2%), while 7 (53.8%) showed no metastasis; VT distribution by Mayo level comprised 7 cases (53.8%) at level 0, 1 case each at levels Ⅰ and Ⅳ (7.7% respectively), and 2 cases each at levels Ⅱ and Ⅲ (15.4% respectively); surgical approaches comprised open surgery (=2, 15.4%), laparoscopic surgery (=6, 46.1%), and robot-assisted laparoscopic surgery (=5, 38.5%); mean operative time was (273±79) min, and intraoperative blood loss was (722±570) mL; mean maximum tumor diameter was (10.8±2.4) cm. All the 13 patients underwent TFE3 protein immunohistochemistry (IHC) staining, with 7 confirmed by fluorescence hybridization (FISH). Tumor recurrence or metastasis occurred in 11 patients (84.6%), and 9 (69.2%) patients died during follow-up. Median PFS was 4 months (1 year PFS rate: 31%), and median OS was 13 months (1 year OS rate: 54%). Survival analysis of 45 -RCC patients revealed statistically significant differences in PFS and OS across all the clinical stages ( < 0.001). The -VT patients exhibited significantly worse PFS and OS than the -non-VT patients ( < 0.001), with persistent significance in stage Ⅲ subgroup analysis ( < 0.05). After PSM, -VT patients showed significantly inferior PFS compared with non--VT (=0.01), though no significant difference was shown between the OS curves (=0.11).

CONCLUSION

-VT predominantly occurs in young females with frequent preoperative metastases. Strongly-positive staining of TFE3 protein in IHC staining and red-green split signals in FISH tests are reliable diagnostic markers. -VT patients exhibit inferior survival compared with -non-VT patients and earlier progression than non--VT patients.