Significance of a frozen section analysis of the ureteral margin in bladder cancer patients treated with radical cystectomy and neoadjuvant chemotherapy

Abstract

Although the clinical utility of a frozen section analysis (FSA) at the time of radical cystectomy (RC) has already been established, its significance and utility in bladder cancer patients receiving neoadjuvant chemotherapy (NAC) have not yet been fully evaluated. We identified 458 patients (937 ureters) who underwent open RC for bladder cancer at our 7 Japanese institutions between 2004 and 2015. Among these patients, 139 (284 ureters) received NAC before RC (NAC group), while 319 (653 ureters) underwent RC alone (non-NAC group). FSA was performed on 356 out of 937 (38.0%) ureters and 179 out of 458 (39.1%) patients. FSA was positive in 30 out of 356 (8.4%) ureters and its sensitivity, specificity, and accuracy were 89.3, 98.5, and 97.8%, respectively. In the NAC group, FSA was performed on 138 out of 284 (48.6%) ureters and 68 out of 139 (48.9%) patients. FSA was positive in 8 out of 138 ureters (5.8%), and its sensitivity, specificity, and accuracy were 77.8, 99.2, and 97.8%, respectively. In the non-NAC group, FSA was performed on 218 out of 653 (33.4%) ureters and 111 out of 319 (34.8%) patients. FSA was positive in 22 out of 218 (10.1%) ureters, and its sensitivity, specificity, and accuracy were 94.7, 98.0, and 97.7%, respectively. No correlation was observed between preoperative clinical factors and FSA positivity in the NAC group; however, in the non-NAC group, the incidence of FSA positivity in the ureters of patients with concomitant CIS in TUR-BT specimens was 8/41 (19.5%), which was significantly higher than that in their counterpart (14/177, 7.9%, p = 0.033). Even in the era of NAC in the management of bladder cancer patients, the performance of FSA does not change and FSA at the time of RC may provide useful diagnostic information.

Accuracy of Frozen Section Analysis of Urethral and Ureteral Margins During Radical Cystectomy for Bladder Cancer: A Systematic Review and Diagnostic Meta-Analysis

“…Table 1 summarizes the characteristics of included studies. Fourteen studies, comprising 8208 patients, were included in the quantitative synthesis [7,13,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36].…”

“…Ten studies provided data on the value of pathologic detection of malignant involvement of the ureter on FSA during RC [13,[21][22][23][24][25][26][27][28]33]. The prevalence of ureteral malignant involvement on FSA and final margin analysis varied from 0.85% (in patients without concomitant CIS) [32] to 35.6% (in patients with concomitant CIS) [32] and from 5.4% [28] to 15% [21], respectively.…”

Intraoperative pathology consultation during urological surgery: Impact on final margin status and pitfalls of frozen section diagnosis

“…Various studies have assessed the diagnostic accuracy of FSA for ureteral margins by comparing with the final histopathology (i.e., frozen section control). In some of these studies, the sensitivity and specificity of FSA for the diagnosis of CIS, urothelial carcinoma, and/or severe dysplasia ranged 45%–89% and 83%–99.8%, respectively 8,10–15 . It has also been documented that 28%–83% of cases with initial abnormal FSA could be converted to a final negative margin by additionally excising ureteral tissue 8,10,12–14 .…”

“…Meanwhile, patients with positive FSA have been shown to have a significantly higher risk of tumor progression or disease‐specific mortality in univariate models, but not in multivariate settings 10,11,14 . Positive FSA diagnosis also tended to correlate with tumor recurrence in patients undergoing neoadjuvant chemotherapy prior to radical cystectomy ( N = 68; p = 0.073), but not in those without neoadjuvant therapy ( N = 111; p = 0.931) 15 . In a more recent study involving 98 patients/196 ureteral FSAs, positive FSA was found to be an independent risk factor for overall survival (hazard ratio [HR] = 4.2; p = 0.016) 16 .…”

“…There was also no significant difference in progression‐free survival between the two cohorts. In the other studies, 15,18,20 the status of final surgical margins in non‐FSA patients, as well as its prognostic significance, was not assessed. Thus, there is no direct evidence to indicate the potential prognostic benefit of performing FSA at the ureteral and/or urethral margins in bladder cancer patients after radical cystectomy, and their utility needs to be further established.…”