Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate‐tolerant cells. (26th October 2017)

• Record Type: Journal Article
• Authors: Porter, Laura H.; Hashimoto, Kohei; Lawrence, Mitchell G.; Pezaro, Carmel; Clouston, David; Wang, Hong; Papargiris, Melissa; Thorne, Heather; Li, Jason; Ryan, Andrew; Norden, Sam; Moon, Daniel; Bolton, Damien M.; Sengupta, Shomik; Frydenberg, Mark; Murphy, Declan G.; Risbridger, Gail P.; Taylor, Renea A.
• Is Part Of: BJU international. Volume 121:Number 6(2018)
• Page Start: 971
• Page End: 978
• Publication Date: 2017-10-26
• Subjects: pathology -- intraductal carcinoma of the prostate -- androgen deprivation therapy -- patient‐derived xenografts -- BRCA -- #PCSM -- #ProstateCancer; Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.14043
• Languages: English
• ISSNs: 1464-4096

Abstract

Abstract : Objective: To determine the relevance of intraductal carcinoma of the prostate (IDC‐P) in advanced prostate cancer by first examining whether IDC‐P was originally present in patients who later developed advanced prostate cancer and then using patient‐derived xenografts (PDXs) to investigate the response of IDC‐P to androgen deprivation therapy (ADT). Materials and Methods: We conducted a retrospective pathology review of IDC‐P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer. Overall survival was calculated using the Kaplan–Meier method. To demonstrate the response of IDC‐P to ADT, we established PDXs from seven patients with familial and/or high‐risk sporadic prostate cancer. After castration and testosterone restoration of host mice, we measured the volume and proliferation of IDC‐P within PDX grafts. Results: We found that IDC‐P was a prominent feature in the primary prostate specimens, present in 63% of specimens and often co‐existing with poorly differentiated adenocarcinoma. Overall survival was similar in patients with or without IDC‐P. In the PDXs from all seven patients, IDC‐P was identified and present at a similar volume to adenocarcinoma. Residual IDC‐P lesions persisted after host castration and, similar to castrate‐tolerant adenocarcinoma, testosterone restoration led to tumour regeneration. Conclusion: The study showed that IDC‐P is prevalent in aggressive prostate cancer and contains cells that can withstand androgen deprivation. Thus, IDC‐P appears functionally relevant in advanced prostate cancer. The presence of IDC‐P may be a trigger to develop innovative clinical management plans.