SUO 2017: Leveraging Salvage Prostatectomy Specimens To Develop Novel Biomarkers Of Radiation Resistance

Washington, DC (UroToday.com) Introduction: Primary radiation therapy (RT) has a relatively high rate of biochemical recurrence of 30-50% in intermediate and high-risk prostate cancer (PC). While recurrence may be a function of advanced disease at the time of RT, the finding of viable radioresistant PC in salvage prostatectomy specimens suggests that some PCs may be intrinsically resistant to RT, according to the authors of this study. Salvage prostatectomy specimens provide foci of both radiation resistant and sensitive areas within the same prostate for comparison. The authors aimed to understand the biological basis of radiation failure by leveraging salvage prostatectomy specimens.

Methods: Using our ex vivo culture system, a prostate explant technique was utilized to evaluate salvage prostatectomy specimens. Pathologists identified regions of the prostate that are consistent with radiation-sensitive and radiation-resistant foci. PC cores were obtained from these regions and cultured. Specimens obtained from these different foci were treated with 2Gy radiation with or without enzalutamide. Evaluation of DNA damage was conducted with quantitative PCR. On a gross pathologic level, given the evaluation of multiple specimens, a grading schematic had been created for determining the level of radiation treatment effect.

Results: Evaluation of over 40 salvage prostatectomy samples demonstrated a distinct grading scheme for radiation effect on PC cells. The effects of radiation therapy with or without enzalutamide to these specimens were further evaluated to determine any differences in DNA damage repair genes in response to radiation.

Conclusion: The findings from this study demonstrate that there exists a biological difference between PC cells that are radiation sensitive to those that are resistant. In this manner, salvage prostatectomy specimens can be leveraged and are being sequenced to identify the novel biomarkers that characterize radiation resistance.

Presented by: Timothy Clinton, UT Southwestern Medical Center in Dallas, TX, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 18th Annual Meeting of the Society of Urologic Oncology, November 29-December 1, 2017 – Washington, DC
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