Introduction: Diagnosis of upper tract urothelial cancer (UTUC) is crucial. In this regard, uretheral systematic biopsies (USB) have never been considered. We aim to investigate the safety and usefulness of USB in the diagnosis of UTUC and its impact on disease management. Methods: We relied on a prospectively maintained database of patients who underwent diagnostic ureteroscopy (URS) for UTUC between 2015-21. USB included at least 2 biopsies in each UT portion: pelvis, proximal, medium, and distal ureter. Perioperative complications were graded using the Clavien-Dindo (CD) classification. We assessed the surgical safety and diagnostic impact of USB and estimated the 2-yr nephroureterectomy free-survival (NFU-FS) according to USB results. Then, we investigated the added value of USB over high-risk tumor variables according to EAU prognostic model. Finally, uni and multivariable logistic regression (MLR) analyses investigated preoperative predictors of positive USB. Results: Overall, 91/360 (25.3%) patients underwent USB. Compared to patients who did not undergo USB, USB did not increase the risk of perioperative and major (CD >3a) complications, nor the risk of readmission (all p>0.05). USB was positive in 43 (47.25%) cases, negative in 30 (33%) patients. 58/300 (19.3%) biopsies were not diagnostic. In 36 (39.5%) patients both USB and biopsy of a suspicious lesion were performed. In 7 (19.4%) cases, USB outperformed the biopsy of the lesion in detecting UTUC. 11 (12%) patients were diagnosed with a distal ureter tumor. In 5 (45.4%) cases USB detected UTUC in other upper tract portions. The 2-yr NFU-FS rates were 87.7% (95CI%: 78.1-98.5) vs 53% (95%CI: 39.4-71.2) (p=0.001) for negative vs positive USB patients. At Cox-regression model accounting for predefined variables, patients with positive USB (vs. negative) had a higher risk of being treated with NFU [Hazard ratio: 3.38, 95%CI:1.46-7.80, p=0.004)]. At MLR analysis, after adjusting for age, pre-operative positive cytology, smoking status, previous bladder cancer and previous UTUC, patients with negative pre-operative CT scan had a higher probability of having a positive USB (Odds ratio: 8.36, 95%CI: 1.57-71.18, p=0.02). Conclusions: USB is a safe procedure and detected a non-visible tumor at URS in one over five patients. Positive USB increases the risk of radical treatment and possibly changes the treatment algorithm in almost 50% of the patients with distal ureteral tumor candidates to conservative management. When UTUC is suspected, patients with preoperative negative CT scan may benefit the most from USB. SOURCE OF Funding: none
