The impact of routine frozen section analysis during nephroureterectomy or segmental ureterectomy for urothelial carcinoma on final surgical margin status and long-term oncologic outcome

The utility of intraoperative frozen section analysis (FSA) at the surgical margins (SMs) in patients with upper urinary tract cancer has not been established. We herein assessed the clinical significance of routine FSA of ureteral SMs during nephroureterectomy (NU) or segmental ureterectomy (SU). A retrospective review of our Surgical Pathology database identified consecutive patients undergoing NU (n=246) or SU (n=42) for urothelial carcinoma from 2004 to 2018. FSA (n=54) was correlated with the diagnosis of frozen section controls, the status of final SMs, and the prognosis of patients. During NU, FSA was performed in 19 (7.7%) patients and was significantly more often requested in cases with ureteral tumor (13.1%) than in those with renal pelvis/calyx tumor (3.5%). Final SMs at the distal ureter/bladder cuff were positive only in non-FSA cases in the entire NU cohort (8.4%; P=0.375) or those with tumor at the lower ureter (57.6%; P=0.046), but not in any of FSA patients (0%). During SU, FSA was performed in 35 (83.3%) cases, including 19 at either proximal or distal SM and 16 at both SMs (SU-FSA2). Final positive SMs were significantly more often detected in non-FSA patients (42.9%) than in all FSA (8.6%; P=0.048) or SU-FSA2 (0%; P=0.020) patients. Overall, FSAs were reported as positive or high-grade carcinoma (n=7), atypical or dysplasia (n=13), and negative (n=34), and all these diagnoses were confirmed accurate on the frozen section controls, except one with a revision from atypical to carcinoma in situ. Meanwhile, 16 (80.0%) of 20 cases with initial positive/atypical FSA achieved negative conversion by excision of additional tissue. Kaplan-Meier analysis revealed that SU-FSA did not significantly reduce the risk of tumor recurrence in the bladder, disease progression, or cancer-specific mortality. Nonetheless, NU-FSA was strongly associated with reduced progression-free (P=0.023) and cancer-specific (P=0.007) survival rates, compared with non-FSA, which may imply a selection bias (e.g., FSA for clinically more aggressive tumors). Performing FSA during NU for lower ureteral tumor, as well as during SU, significantly reduced the risk of positive SMs. However, routine FSA for upper urinary tract cancer failed to considerably improve long-term oncologic outcome.