Intraductal carcinoma of the prostate can evade androgen-deprivation, with emergence of castrate tolerant cells

To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer, we first examined whether IDC-P was originally present in patients who later developed advanced prostate cancer and then used patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT).

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 men 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.

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.

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. This article is protected by copyright. All rights reserved.

BJU international. 2017 Oct 04 [Epub ahead of print]

Laura H Porter, Kohei Hashimoto, Mitchell G Lawrence, Carmel Pezaro, David Clouston, Hong Wang, Melissa Papargiris, Heather Thorne, Jason Li, kConFab , Andrew Ryan, Sam Norden, Daniel Moon, Damien M Bolton, Shomik Sengupta, Mark Frydenberg, Declan G Murphy, Gail P Risbridger, Renea A Taylor

Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Victoria, Australia, 3800., TissuPath, Mount Waverley, Victoria, Australia, 3149., kConFab, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia, 3000., Bioinformatics Core, Peter MacCallum Cancer Centre, University of Melbourne, Victoria, Australia, 3000., Epworth Healthcare, Richmond, Victoria, Australia, 3121., Department of Urology, Austin Hospital, Melbourne Heidelberg, Victoria, Australia, 3084., Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, Australia, 3000.

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