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Title: Ductal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival.
Austin Authors: Chow, Ken;Bedő, Justin;Ryan, Andrew;Agarwal, Dinesh;Bolton, Damien M ;Chan, Yee ;Dundee, Philip;Frydenberg, Mark;Furrer, Marc A;Goad, Jeremy;Gyomber, Dennis ;Hanegbi, Uri;Harewood, Laurence;King, Dennis;Lamb, Alastair D;Lawrentschuk, Nathan;Liodakis, Peter ;Moon, Daniel;Murphy, Declan G;Peters, Justin S;Ruljancich, Paul;Verrill, Clare L;Webb, David ;Wong, Lih-Ming ;Zargar, Homayoun;Costello, Anthony J;Papenfuss, Anthony T;Hovens, Christopher M;Corcoran, Niall M
Affiliation: School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia
Australian Prostate Centre, North Melbourne, Victoria, Australia
Department of Urology, Frankston Hospital, Frankston, Victoria, Australia
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
TissuPath Specialist Pathology, Mount Waverley, Victoria, Australia
Department of Surgery, University of Melbourne, Parkville, Victoria, Australia
Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia
Department of Urology, Western Health, Footscray, Victoria, Australia
Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Epworth Eastern, Box Hill, Victoria, Australia
Department of Urology, St Vincent's Health, Fitzroy, Victoria, Australia
Department of Urology, Alfred Health, Melbourne, Victoria, Australia
Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland..
Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia
Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia
Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom..
Department of Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom..
Issue Date: May-2021
Date: 2021-03-05
Publication information: European Journal of Cancer 2021; 148: 440-450
Abstract: Ductal adenocarcinoma is an uncommon prostate cancer variant. Previous studies suggest that ductal variant histology may be associated with worse clinical outcomes, but these are difficult to interpret. To address this, we performed an international, multi-institutional study to describe the characteristics of ductal adenocarcinoma, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. Patients with ductal variant histology from two institutional databases who underwent radical prostatectomies were identified and compared with an independent acinar adenocarcinoma cohort. After propensity score matching, the effect of the presence of ductal adenocarcinoma on time to biochemical recurrence, initiation of salvage therapy and the development of metastatic disease was determined. Deep whole-exome sequencing was performed for selected cases (n = 8). A total of 202 ductal adenocarcinoma and 2037 acinar adenocarcinoma cases were analysed. Survival analysis after matching demonstrated that patients with ductal variant histology had shorter salvage-free survival (8.1 versus 22.0 months, p = 0.03) and metastasis-free survival (6.7 versus 78.6 months, p < 0.0001). Ductal variant histology was consistently associated with RB1 loss, as well as copy number gains in TAP1, SLC4A2 and EHHADH. The presence of any ductal variant adenocarcinoma at the time of prostatectomy portends a worse clinical outcome than pure acinar cancers, with significantly shorter times to initiation of salvage therapies and the onset of metastatic disease. These features appear to be driven by uncoupling of chromosomal duplication from cell division, resulting in widespread copy number aberration with specific gain of genes implicated in treatment resistance.
DOI: 10.1016/j.ejca.2020.12.030
Journal: European Journal of Cancer
PubMed URL: 33678516
Type: Journal Article
Subjects: Ductal adenocarcinoma
Metastasis-free survival
Prostate cancer
Appears in Collections:Journal articles

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