A prognostic model for survival of patients with metastatic upper tract urothelial carcinoma with first-line systemic therapy.

868 Background: Upper tract urothelial carcinoma (UTUC) presents distinct clinicopathological, molecular features, and biological behaviors compared to urothelial bladder carcinoma (UBC). Currently, no prognostic model exists for metastatic UTUC (mUTUC). This study aimed to develop a prognostic model for mUTUC patients receiving first-line systemic therapy. Methods: A total of 476 patients with mUTUC who received first-line systemic therapy at Peking University Cancer Hospital from January 2005 to March 2024 were included in the analysis. Patients were randomly assigned to development and validation cohorts in a 3:1 ratio, with potential prognostic factors recorded prospectively. Univariate Cox regression analysis identified clinical and laboratory factors significantly associated with median overall survival (mOS) in the development cohort, followed by multivariate Cox regression analysis to determine independent prognostic factors. These factors were utilized to develop a prognostic model. Internal validation was conducted using the validation cohort. Results: After a median follow-up of 51.8 months, 321 patients (67.4%) had died, with a mOS of 26.6 months. The median age at diagnosis was 63 years, with 58.4% males. Common visceral metastatic organs included lung (37.8%), liver (17.9%), and adrenal gland (7.4%). The most frequent first-line treatment option was platinum-containing chemotherapy (63.7%). The number of metastatic organs ≥ 3, Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 1, time to distant metastasis (TTDM) < 12 months, white blood cell (WBC) count > upper limit of normal (ULN), and alkaline phosphatase (ALP) level > ULN were identified as independent prognostic risk factors for mUTUC (Table). A prognostic model for mUTUC was developed, in which the patients were stratified into three risk categories: favorable (0 risk factors, mOS 65.0 months [95% CI 35.5–94.6]), intermediate (1 risk factor, mOS 32.0 months [95% CI 25.8–38.2]), and poor (2+ risk factors, mOS 16.0 months [95% CI 12.1–19.9]) ( p < 0.05). The model's concordance statistic (c-statistic) was 0.71 in the development cohort and 0.72 in the validation cohort. Conclusions: We developed and validated a prognostic model for mUTUC patients receiving first-line systemic therapy, which can inform future clinical practice and trial designs. Results of multivariate analysis. Variables P Hazard Ratio (95% CI) Reference Category TTDM <0.01 3.01 (2.13 ~ 4.26) ≥ 12 months ECOG PS <0.01 2.28 (1.30 ~ 3.97) ≤ 1 Number of Metastatic Organs 0.01 1.41 (1.04 ~ 1.91) < 3 WBC <0.01 1.89 (1.21 ~ 2.95) ≤ ULN ALP 0.02 1.71 (1.10 ~ 2.64) ≤ ULN