Novel perioperative tetrafecta is independently associated with oncological outcomes after radical nephroureterectomy for upper tract urothelial carcinoma: a retrospective cohort study

Background: Previously proposed composite quality metrics for radical nephroureterectomy (RNU) often incorporate early recurrence outcomes, which limits their validity as immediate perioperative indicators and introduces a methodological overlap between quality metrics and oncologic endpoints. We evaluated a novel perioperative composite metric and its association with long-term oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC). Methods: We retrospectively analyzed 984 consecutive patients who underwent RNU between 2015 and 2024 at a tertiary referral center. The perioperative composite metric (tetrafecta) was defined as intravesical distal ureter cuffing, negative surgical margins, no intraoperative transfusion, and immediate intravesical chemotherapy instillation. The primary endpoint was metastatic progression, and the secondary endpoints included intravesical recurrence and overall survival. Multivariable Cox regression, stratified by surgical era, was used for time-to-event analyses, and competing-risk regression was applied for intravesical recurrence. Results: The tetrafecta was achieved in 136 (13.8%) patients. During the follow-up, 204 metastatic progressions, 310 intravesical recurrences, and 200 deaths occurred. In multivariable analyses, tetrafecta achievement was independently associated with reduced risks of metastatic progression (adjusted hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.30–0.99; P = 0.045) and intravesical recurrence (adjusted HR: 0.54, 95% CI: 0.34–0.87; P = 0.011), but not overall survival (adjusted HR: 0.49, 95% CI: 0.22–1.07; P = 0.073). Major complications (Clavien–Dindo grade ≥3) were comparable between the groups (3.7% vs. 2.6%; P = 0.406). Conclusions: The perioperative tetrafecta was independently associated with reduced risks of metastatic progression and intravesical recurrence after RNU, without increasing postoperative morbidity. By avoiding the methodological overlap between quality indicators and oncologic endpoints, this approach enables real-time surgical quality assessment. These findings support its use as a pragmatic benchmarking tool for evaluating clinical performance and facilitating quality improvement in UTUC management.