Highlights
- •Ductal adenocarcinoma of the prostate is more clinically aggressive than acinar adenocarcinoma.
- •Ductal adenocarcinoma has shorter time to metastasis.
- •This is the first large non-registry–based study to use metastasis-free survival as an end-point.
- •RB1 loss may be a key molecular driver in clinical difference.
Abstract
Background
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.
Methods
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).
Results
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.
Conclusions
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.
Keywords
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Article info
Publication history
Published online: March 05, 2021
Accepted:
December 19,
2020
Received in revised form:
December 9,
2020
Received:
September 3,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Cribriform architecture prostatic adenocarcinoma in needle biopsies is a strong independent predictor for lymph node metastases in radical prostatectomyEuropean Journal of CancerVol. 148
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