Urinary cytology has a poor performance for predicting invasive or high-grade upper-tract urothelial carcinoma

• To evaluate the diagnostic accuracy of urine cytology for detecting aggressive disease in a multi-institutional cohort of patients undergoing extirpative surgery for upper-tract urothelial carcinoma (UTUC).

• We reviewed the records of 326 patients with urinary cytology data who underwent a radical nephroureterectomy or distal ureterectomy without concurrent or previous bladder cancer. • We assessed the association of cytology (positive, negative and atypical) with final pathology. Sensitivity and positive predictive value (PPV) of a positive (± atypical) cytology for high-grade and muscle-invasive UTUC was calculated.

• On final pathology, 53% of patients had non-muscle invasive disease (pTa, pTis, pT1) and 47% had invasive disease (≥ pT2). Low-grade and high-grade cancers were present in 33% and 67% of patients, respectively. • Positive, atypical and negative urine cytology was noted in 40%, 40% and 20% of cases. Positive urinary cytology had sensitivity and PPV of 56% and 54% for high-grade and 62% and 44% for muscle-invasive UTUC. • Inclusion of atypical cytology with positive cytology improved the sensitivity and PPV for high-grade (74% and 63%) and muscle-invasive (77% and 45%) UTUC. Restricting analysis to patients with selective ureteral cytologies further improved the diagnostic accuracy when compared with bladder specimens (PPV > 85% for high-grade and muscle-invasive UTUC).

• In this cohort of patients with UTUC treated with radical surgery, urine cytology in isolation lacked performance characteristics to accurately predict muscle-invasive or high-grade disease. • Improved surrogate markers for pathological grade and stage are necessary, particularly when considering endoscopic modalities for UTUC.