The Accuracy of Sequential Urethral Frozen Section and its Impact on Urethral Recurrence After Radical Cystectomy

Published:April 21, 2022DOI:



      To assess the accuracy of frozen section analysis (FSA) for detecting and eliminating malignant urethral margins during radical cystectomy (RC) for bladder cancer (BC) and its impact on urethral recurrence.


      Urethral margins were initially examined by FSA in 217 patients at RC. When positive, additional resections were performed. Subsequently, all specimens were re-examined on formalin-fixed, paraffin-embedded sections (FFPE). Malignancy was defined as either the presence of carcinoma in situ, high-grade or invasive tumor cells at the urethral margin. Kaplan-Meier analysis was used to assess the impact of the final urethral margin status on urethral recurrence. Multinomial logistic regression addressed independent risk factors for a positive final urethral margin.


      At initial examination, urethral margins were positive on FSA and FFPE in 21 (9.7%) and 17 (7.8) patients, respectively. The corresponding sensitivity, specificity, positive and negative predictive values were 88.2%, 97.0%, 71.4% and 99.0% (overall accuracy: 96.3%). After initial FSA, 23 patients (including 2 with equivocal histological findings) received re-resections (median: 1, total range: 1-3). Persistent positive margins were detected on FSA in 10 (43.5%) while none of these margins were positive on FFPE (overall accuracy: 52.2%). A positive urethral FSA at initial assessment was the only independent risk for a positive final urethral margin. The 3-year urethral recurrence-free survival was 99.1% for patients with negative margins on initial assessment (I), 100% for those with negative final margins after re-resection (II) and 83.3% for patients with positive final margins (III; P= .013 for I/II vs. III).


      The accuracy of FSA for detecting malignant urethral margins is high on initial examination but drops considerably in case of re-resection while most positive margins at initial FSA are converted to negative final ones on FFPE. Conversion of a positive to a negative margin was associated with a lower risk of urethral recurrence.



      FSA (frozen section analysis), RC (radical cystectomy), FFPE (formalin-fixed paraffine-embedded), BC (bladder cancer), PD (primary diagnosis), MIBC (muscle-invasive bladder cancer), STSM (soft-tissue surgical margin), TURBT (transurethral bladder tumor resection), BCG (Bacille-Calmette-Guerin), MMC (Mitomycin C), CIS (carcinoma in situ), IQR (interquartile range), PPV (positive predictive value), ONB (orthotopic neobladder), UR (urethral recurrence), TUR (transurethral resection)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Donat SM.
        Argument against frozen section analysis of distal ureters in transitional cell bladder cancer.
        Nat Clin Pract Urol. 2008; 5: 538-539
        • Labbate C
        • Werntz RP
        • Adamic B
        • Steinberg GD.
        The impact of omission of intraoperative frozen section prior to orthotopic neobladder reconstruction.
        J Urol. 2019; 202: 763-769
        • Osman Y
        • Mansour A
        • El-Tabey N
        • Abdel-Latif M
        • Mosbah A
        • Hekal I
        • et al.
        Value of routine frozen section analysis of urethral margin in male patients undergoing radical cystectomy in predicting prostatic involvement.
        Int Urol Nephrol. 2012; 44: 1721-1725
        • Sureka SK
        • Yadav A
        • Arora S
        • Kapoor R
        • Mandhani A.
        Is frozen section analysis of the urethra at the time of radical cystectomy and orthotopic neobladder urinary diversion mandatory?.
        Indian J Urol. 2015; 31: 349-353
        • Gakis G
        • Ali-El-Dein B
        • Babjuk M
        • Hrbacek J
        • Macek P
        • Burkhard FC
        • et al.
        Urethral recurrence in women with orthotopic bladder substitutes: A multi-institutional study.
        Urol Oncol. 2015; 33 (e17-23): 204
        • von Rundstedt FC
        • Mata DA
        • Shen S
        • Li Y
        • Godoy G
        • Lerner SP.
        Transurethral biopsy of the prostatic urethra is associated with final apical margin status at radical cystoprostatectomy.
        J Clin Urol. 2016; 9: 404-408
        • Gaya JM
        • Matulay J
        • Badalato GM
        • Holder DD
        • Hruby G
        • McKiernan J.
        The role of preoperative prostatic urethral biopsy in clinical decision-making at the time of radical cystectomy.
        Can J Urol. 2014; 21: 7228-7233
        • Kassouf W
        • Spiess PE
        • Brown GA
        • Liu P
        • Grossman HB
        • Dinney CP
        • et al.
        Prostatic urethral biopsy has limited usefulness in counseling patients regarding final urethral margin status during orthotopic neobladder reconstruction.
        J Urol. 2008; 180 (discussion 7): 164-167
        • Gakis G
        • Efstathiou J
        • Lerner SP
        • Cookson MS
        • Keegan KA
        • Guru KA
        • et al.
        ICUD-EAU International Consultation on Bladder Cancer 2012: radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder.
        Eur Urol. 2013; 63: 45-57
        • Cheng L
        • Montironi R
        • Davidson DD
        • Lopez-Beltran A
        Staging and reporting of urothelial carcinoma of the urinary bladder.
        Mod Pathol. 2009; 22 (Suppl): S70-S95
        • Edge SB
        • Compton CC.
        The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.
        Ann Surg Oncol. 2010; 17: 1471-1474
        • Nelles JL
        • Konety BR
        • Saigal C
        • Pace J
        • Lai J
        Urologic Diseases in America P. Urethrectomy following cystectomy for bladder cancer in men: practice patterns and impact on survival.
        J Urol. 2008; 180 (discussion 6-7): 1933-1936
        • Gakis G
        • Black PC
        • Bochner BH
        • Boorjian SA
        • Stenzl A
        • Thalmann GN
        • et al.
        Systematic Review on the Fate of the Remnant Urothelium after Radical Cystectomy.
        Eur Urol. 2017; 71: 545-557