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.
European journal of cancer (Oxford, England : 1990). 2021 Mar 04 [Epub ahead of print]
Ken Chow, Justin Bedő, Andrew Ryan, Dinesh Agarwal, Damien Bolton, Yee Chan, Philip Dundee, Mark Frydenberg, Marc A Furrer, Jeremy Goad, Dennis Gyomber, Uri Hanegbi, Laurence Harewood, Dennis King, Alastair D Lamb, Nathan Lawrentschuk, Peter Liodakis, Daniel Moon, Declan G Murphy, Justin S Peters, Paul Ruljancich, Clare L Verrill, David Webb, Lih-Ming Wong, Homayoun Zargar, Anthony J Costello, Anthony T Papenfuss, Christopher M Hovens, Niall M Corcoran
Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia. Electronic address: ., Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Computing and Information Systems, University of Melbourne, Melbourne, Victoria, Australia., TissuPath Specialist Pathology, Mount Waverley, Victoria, Australia., Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Urology, Western Health, Footscray, Victoria, Australia., Department of Urology, Austin Health, Heidelberg, 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., Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia; Cabrini Institute, Cabrini Health, Malvern, Victoria, Australia., Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Urology, St Vincent's Health, Fitzroy, Victoria, Australia., Department of Urology, Alfred Health, Melbourne, Victoria, Australia., Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia., Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom., Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia; Department of Urology, Austin Health, Heidelberg, Victoria, Australia; Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia; Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia., Epworth Eastern, Box Hill, Victoria, Australia., Department of Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Department of Urology, Austin Health, Heidelberg, Victoria, Australia; Department of Urology, St Vincent's Health, Fitzroy, Victoria, Australia., Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia; Australian Prostate Centre, North Melbourne, Victoria, Australia., Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia; School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria, Australia., Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia., Department of Surgery, University of Melbourne, Parkville, Victoria, Australia; Urology Unit, Royal Melbourne Hospital, Parkville, Victoria, Australia; Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia; Department of Urology, Frankston Hospital, Frankston, Victoria, Australia.