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Histologic characterization of the post-radiation urethral stenosis in men treated for prostate cancer

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Abstract

Purpose

To evaluate histological changes in stenotic urethral tissue post-radiation therapy. Treatment of prostate cancer by radiation therapy carries a risk of off-target injury to the membranous urethra causing urethral stenosis. Limited characterization of post-radiation urethral stenosis exists in the literature. We hypothesize that specific histopathologic parameters distinguish this stricture etiology.

Methods

Eighty-two consecutive patients with membranous urethral stenosis underwent urethroplasty between 2013 and 2018. Seventy specimens (86.4%) were available for evaluation: 51 from patients without radiation exposure and 19 from patients with history of radiation therapy for prostate cancer. All specimens were reviewed by a pathologist blinded to patient/stricture information. Histological scoring system was used for the quantification of collagen density, collagen organization, hyalinized fibrosis, vascular density, spindle-cell change, necrosis, hemorrhage, fat entrapment, vacuolation, acute and chronic inflammation, and foreign-body giant cells. Differences in histologic outcomes between groups were statistically analyzed.

Results

Post-radiation specimens had a higher collagen density (p = 0.01), higher collagen organization (p = 0.001), increased hyalinized fibrosis (p = 0.03), fat entrapment (p = 0.005) and spindle cell change (p = 0.005) when compared to membranous specimens without prior exposure to radiation. Post-radiation specimens also had a significantly decreased vascularity compared to specimens of non-radiated etiology (p = 0.0005). Fibrous connective tissue degenerative change with vacuolation was pronounced in post-radiation specimens and seldom seen in those without radiation (p = 0.0001).

Conclusions

Membranous urethral stenosis following radiation demonstrates specific histologic characteristics including vascular loss and increased scarring (collagen density, organization). This histologic grading system may be used in grading severity of radiation damage, and conceivably adopted for correlation with clinical outcomes.

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Authors and Affiliations

Authors

Contributions

MH: project development, data collection, data analysis, manuscript writing, and manuscript editing. SB: protocol development, project development, data collection, manuscript writing, and manuscript editing. MD: data collection, data management, data analysis, and manuscript editing. GL: project development, data collection, data analysis, manuscript writing, and manuscript editing. TC: protocol development, data collection, and manuscript writing. DN: protocol development, project development, data collection, data management, data analysis, manuscript writing, and manuscript editing.

Corresponding author

Correspondence to D. Nikolavsky.

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The authors declare that they have no conflict of interest and received no funding for this project.

Research involving human participants

All procedures performed in these studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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No identifiable personal data were used for this retrospective study.

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Hughes, M., Caza, T., Li, G. et al. Histologic characterization of the post-radiation urethral stenosis in men treated for prostate cancer. World J Urol 38, 2269–2277 (2020). https://doi.org/10.1007/s00345-019-03031-y

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  • DOI: https://doi.org/10.1007/s00345-019-03031-y

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