Introduction: According to EAU guidelines, second-look ureteroscopy (SU) could be performed 6-8 weeks after primary endoscopic treatment. We aimed at assessing the impact of positive SU on radical nephroureterectomy-free survival (RNU-FS) and cancer specific survival (CSS) in patients endoscopically treated (URS) for a suspicion of upper tract urothelial carcinoma (UTUC). Methods: We relied on a prospectively maintained single-institution database (2015-2021) of patients with a suspicion of UTUC. Kaplan-Meyer method estimated the 2-year RNU-FS and CSS according to SU results. Multivariable Cox regression (MCR) analyses were implemented to investigate the relationship between SU outcome and the probability of RNU-FS and CSS after adjusting for age, previous radical cystectomy, tumor grade, focality and dimension. Finally, multivariable logistic regression (MLR) analysis investigated predictors of negative SU after adjusting for tumor and patients’ characteristics. Results: Overall, among 360 patients undergone URS, 85 (23.6%) patients underwent SU. No difference emerged between the two cohorts (positive vs negative SU) in terms of previous history of urothelial cancer, tumor focality and histology grading of the primary lesion. In positive SU group, tumors were larger (>20mm, p=0.03) and classified as high-risk (p < 0.001). SU detected tumors in 38 (44.7%) cases. After a median follow-up of 35 (IQR: 15-56) months, 2 (5.2%) and 11 (28.9%) underwent upfront and subsequent RNU in the positive SU cohort, respectively. When comparing the two cohorts, the 2-yr RNU-FS rates were 96.7% (95% CI 90.7-100) and 64.7% (95% CI 50.9-82.2) (p=0.001), while the 2-yr CSS rates were 97.8% (95% CI 93.6-100) and 90.3% (95% CI 80.4-100) (p=0.32), respectively. At MCR analyses, positive SU (HR: 4.56, 95%CI 0.91-22.81, p=0.04) and tumor grade (HR: 3.87, 95%CI 1.08-13.77, p=0.03) were predictors of radical treatment. At MLR, patients with unifocal, low grade tumor with a dimension <10mm had higher probability to have a negative SU (OR: 3.68, 95%CI 1.50-9.44, p=0.005) compared to patients with large, high grade and multifocal tumor. Conclusions: Almost 45% of candidates to SU are diagnosed with UTUC, especially when harboring high-risk features at first URS. Positive SU is associated with higher rates of subsequent radical treatment, which reflects in a similar CSS when compared to patients with negative SU. In patients with unifocal, low grade and small UTUC, the replacement of SU with CT scan could be considered. SOURCE OF Funding: No
