Clinical Determinants of Extraurinary Tract Recurrence and Survival after Radical Surgery for pT2 Upper Tract Urothelial Carcinoma

SIMPLE SUMMARY: Although upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy in Western countries, recurrence and distant metastasis are common even after definitive surgery. Many prognostic factors have been identified from previous studies, allowing clinicians to better stratify risk to select patients for perioperative systemic therapy; however, the applicability of adjuvant chemotherapy for patients with stage II UTUC after radical surgery remains unclear. In this study, we found that patients with primary tumor location at ureter or renal pelvis plus synchronous ureter had more frequent disease relapse and worse long-term oncological outcomes than other patients. Male sex, older age, history of previous bladder cancer, and positive surgical margins remain important unfavorable prognostic factors for recurrence and survival. Additional treatment and closer surveillance in patients with these negative prognostic factors are warranted despite complete pathological removal of the tumor. ABSTRACT: Background: Oncologic outcomes for pT2N0M0 upper tract urothelial carcinoma (UTUC) after nephroureterectomy are not well defined, with most previous studies focused on a heterogeneous population. Therefore, we aimed to investigate the clinical determinants of extraurinary tract recurrence and survival after radical surgery in patients with localized UTUC. Methods: We retrospectively identified 476 patients with pT2N0M0 UTUC who underwent radical nephroureterectomy or ureterectomy between October 2002 and March 2022. To evaluate the prognostic impact, patients were divided into renal pelvic, ureteral, and both-region (renal pelvis plus synchronous ureter) groups based on tumor location. The outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Associations were evaluated using multivariable Cox regression analyses for prognostic factors and Kaplan–Meier analyses for survival curves. Results: The renal pelvic, ureteral, and both-region groups consisted of 151 (31.7%), 314 (66.0%), and 11 (2.3%) patients, respectively. Kaplan–Meier analyses comparing the three tumor types showed significant differences in 5-year RFS (83.6% vs. 73.6% vs. 52.5%, p = 0.013), CSS (88.6% vs. 80.7% vs. 51.0%, p = 0.011), and OS (83.4% vs. 70.1% vs. 45.6%, p = 0.002). Multivariable analyses showed that age >60 years, previous bladder cancer history, ureteral involvement (ureteral and both-regional groups), and positive surgical margins were significant negative prognostic factors for the studied outcomes. Conclusions: Patients with pT2 UTUC and presence of ureteral involvement had more frequent disease relapse. Subsequent adjuvant therapy regimens and close follow-up in patients with negative prognostic factors are warranted despite complete pathological removal of the tumor.