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

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.

• Authors: 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
• Journal: BJU international (BJU Int) Vol. 121 Issue 6 Pg. 971-978 (06 2018) ISSN: 1464-410X [Electronic] England
• PMID: 28977728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Chemical References

• Androgen Antagonists

Topics

• Adenocarcinoma (pathology)
• Aged
• Aged, 80 and over
• Androgen Antagonists (therapeutic use)
• Animals
• Carcinoma, Ductal (drug therapy, pathology)
• Heterografts (pathology)
• Humans
• Kaplan-Meier Estimate
• Male
• Mice, Inbred NOD
• Mice, SCID
• Middle Aged
• Prostatic Neoplasms, Castration-Resistant (drug therapy, pathology)
• Retrospective Studies
• Transplantation, Heterologous
• Xenograft Model Antitumor Assays (methods)