Diagnostic accuracy of ureteroscopic biopsy for upper tract urothelial carcinoma: implications for kidney-sparing therapy selection

Abstract Background Radical nephroureterectomy (RNU) remains the gold standard for high-risk upper tract urothelial carcinoma (UTUC). However, renal preservation is increasingly emphasized for patients with low-grade disease or impaired renal function. Objective To evaluate the diagnostic performance of URS biopsy compared to final pathologic findings after radical nephroureterectomy and to assess the clinical implications for treatment selection. Materials & methods We retrospectively analyzed 913 patients who underwent radical nephroureterectomy for UTUC at a single tertiary center. Among these, 164 patients underwent preoperative URS with biopsy, and 125 had both URS grade and final pathologic grade available for concordance analysis. Diagnostic performance metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen’s kappa coefficient were calculated. Risk factors for undergrading were identified using multivariable logistic regression. Results The overall concordance between URS biopsy and final pathology was 82.4% (103/125). However, marked discordance was observed in low-grade URS biopsies, with an undergrading rate of 58.6% (17/29 cases upgraded to high-grade on final pathology). The PPV for low-grade URS biopsy was only 41.4%, whereas the PPV for high-grade URS biopsy was excellent at 94.8%. Cohen’s kappa was 0.423, indicating moderate agreement. Risk factors for undergrading included age <65 years (OR 2.66, p = 0.004), renal pelvis location (OR 2.59, p = 0.037), and multifocal disease (OR 2.12, p = 0.044). Patients undergoing URS biopsy had higher bladder recurrence rates (29.8% vs. 22.3% vs. 20.5%, p = 0.020) despite not being an independent predictor at multivariate analysis ( p = 0.289). Conclusion URS biopsy demonstrates high undergrading rates (58.6%) and low PPV (41.4%) for low-grade tumors, making it unreliable for selecting patients for kidney-sparing ablative therapies. High-grade URS biopsies reliably predict high-grade disease. Alternative risk stratification strategies are needed to safely identify candidates for nephron-sparing approaches.