Among patients with adenocarcinoma of the urinary bladder (ADKUB), prognostic analysis of urachal ADKUB is relatively limited, and there is no unified staging system. To investigate the impact of tumor location (urachal vs. nonurachal) on ADKUB, we evaluated the survival outcomes of urachal ADKUB and conducted a comparative analysis with nonurachal ADKUB after stage-stratified. We retrospectively collected clinicopathological and survival data from 82 patients with bladder adenocarcinoma treated at a single center, including 31 with urachal ADKUB and 51 with nonurachal ADKUB. To compare the survival outcomes with nonurachal ADKUB, a unified TNM staging system was first applied to urachal ADKUB. Subsequently, both cohorts were grouped into pT1-T2 and pT3-T4 categories for stage-stratified survival analysis. Urachal ADKUB patients were younger and less likely to harbor comorbidities, with 24 patients (77.4%) receiving partial cystectomy and 7 patients (22.6%) receiving radical cystectomy. Urachal ADKUB was more likely to be Mucinous ADKUB (48.4% vs. 15.7%). The 5-year cancer-specific survival (CSS) and recurrence-free survival (RFS) were similar between the 2 groups (60.9% and 47.4% in urachal ADKUB vs. 52.2% and 40.7% in nonurachal ADKUB, respectively). When applying the unified TNM-based staging system, urachal ADKUB showed a possible trend toward better cancer-specific survival, which was more pronounced in patients with locally advanced and metastatic disease (pT3-T4 or higher; P = .048). On multivariate analysis, pathologic T stage (hazard ratio [HR], 4.721) and cardiovascular diseases (HR, 2.616) remained significantly associated with CSS in all patients. Poorly differentiated tumor (HR, 2.039) remained significantly associated with RFS. Compared with nonurachal ADKUB, urachal ADKUB is relatively rare and shows a distinct histological distribution and clinicopathological features. Urachal ADKUB has a prognosis broadly comparable to nonurachal ADKUB, with a possible survival advantage in advanced disease that warrants further validation.

Combination therapy with enfortumab vedotin plus pembrolizumab (EV+P) is now the preferred first-line (1L) therapy for advanced urothelial carcinoma (aUC), but prognostic indicators for patients on 1L EV+P have not yet been described. We conducted a retrospective cohort study of patients receiving 1L EV+P for aUC. We analyzed deidentified electronic health record data from the Flatiron Health database to identify adults with aUC who initiated EV+P between April 3, 2023 and December 31, 2024. Inclusion required absence of death, disease progression, or second line therapy start within 30 days of EV+P initiation, as well as documented weight measurements at the time of EV+P initiation (i.e., day 0) and day 28. We used Cox proportional hazards modeling with stabilized inverse probability treatment weighting (IPTW) to evaluate the association of early on-treatment weight loss with overall survival (OS), progression-free survival (PFS), and time to EV discontinuation. A total of 401 patients met study criteria. Of these, 78 patients (19.5%) experienced ≥ 5% weight loss by day 28 following EV+P initiation. Early on-treatment weight loss was associated with inferior OS (median 12.8 vs. 20.4 months; IPTW-adjusted HR [aHR] = 2.04 [1.41-2.95], P = 1.9 × 10-4), but not with PFS (aHR = 1.22 [0.89-1.65], P = .22) or time to EV discontinuation (aHR = 1.30 [0.96-1.77], P = .090). The association of early on-treatment weight loss with OS was conserved in subgroup analyses stratifying patients by baseline albumin or BMI. Early weight loss ≥5% occurred in one fifth of patients receiving 1L EV+P treatment and was associated with inferior overall survival.