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

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

Research output: Contribution to journalArticleResearchpeer-review

11 Citations (Scopus)

Abstract

Objectives: 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).

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 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.

Results: 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: 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.
Original languageEnglish
Pages (from-to)971-978
Number of pages8
JournalBJU International
Volume121
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • prostate cancer
  • pathology
  • intraductal carcinoma of the prostate
  • androgen deprivation therapy
  • patient-derived xenografts
  • BRCA

Cite this

Porter, L. H., Hashimoto, K., Lawrence, M. G., Pezaro, C., Clouston, D., Wang, H., Papargiris, M., Thorne, H., Li, J., Investigators, K., Ryan, A., Norden, S., Moon, D., Bolton, D. M., Sengupta, S., Frydenberg, M., Murphy, D. G., Risbridger, G. P., & Taylor, R. A. (2018). Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells. BJU International, 121(6), 971-978. https://doi.org/10.1111/bju.14043