Risk stratification of high-risk muscle invasive upper urinary tract urothelial carcinoma: multi-institutional study.

Purpose: This study aimed to analyze a large multi-institutional UTUC database to identify prognostic factors in patients with organ-confined and non-organ-confined disease, and to further stratify pT2 patients using a nomogram to identify high-risk subgroups who may benefit from adjuvant therapy.

Methods: The records of patients diagnosed with UCTC who underwent nephroureterectomy from 1988 to 2022 at 15 hospitals in Taiwan were retrospectively reviewed. The outcomes evaluated were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) after nephroureterectomy.

Results: A total of 2635 patients were included: 1935 with organ-confined (pTis/pTa/pT1/pT2 stage) disease, and 700 with non-organ confined (pT3/pT4 stage) disease. Significant risk factors for poor survival in patients with organ-confined disease were age ≥ 70 years, ureter involvement, high pathological T stage (pT2), multiplicity, lymphovascular invasion, and eGFR ≤ 44 ml/min/1.73 m². In patients with non-organ-confined disease, risk factors included male sex, age ≥ 70 years, ureter involvement, high pathological T stage (pT4), multiplicity, eGFR ≤ 44 ml/min/1.73 m², tumor necrosis, variant UC cell type, and smoking. In patients with pT2 UTUC, those classified as high risk based on a nomogram-derived total score > 115 had significantly worse OS (P < 0.0001) and CSS (P = 0.025) compared to those with a score ≤ 115 (low risk).

Conclusions: Patients with high-risk pT2 UTUC had significantly worse survival outcomes compared to those with low-risk pT2 UTUC. These findings suggest that further refinement of clinical trial designs is needed to better identify high-risk pT2 UTUC patients who may benefit from more aggressive treatment strategies, such as adjuvant therapy, while minimizing unnecessary systemic therapy in low-risk pT2 UTUC patients. Future studies should validate these findings and help establish the true value of systemic therapy for this patient population.