Surgery (St Vincent's) - Research Publications

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Author: Bolton, Damien × Author: Murphy, Declan × Author: Sengupta, Shomik × End date: 2019 × Start date: 2018 × Type: Journal Article ×

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    Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells
    Porter, LH ; Hashimoto, K ; Lawrence, MG ; Pezaro, C ; Clouston, D ; Wang, H ; Papargiris, M ; Thorne, H ; Li, J ; Ryan, A ; Norden, S ; Moon, D ; Bolton, DM ; Sengupta, S ; Frydenberg, M ; Murphy, DG ; Risbridger, GP ; Taylor, RA (WILEY, 2018-06)
    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.