Original ResearchDuctal variant prostate carcinoma is associated with a significantly shorter metastasis-free survival
Introduction
Ductal adenocarcinoma (DAC) of the prostate is an uncommon non-acinar variant of prostatic carcinoma. In its pure form, it accounts for only 0.2–0.8% of all prostate cancers [[1], [2], [3]]. However, it can be identified intermixed with acinar adenocarcinoma (AAC) in up to 3.2% of all radical prostatectomy specimens [4].
Although the presence of ductal histology was initially believed to be associated with a better prognosis [5], more recent studies suggest the contrary [[6], [7], [8]]. Some studies suggest that biochemical recurrence (BCR) rates are higher for DAC and may even progress without a significant rise in prostate-specific antigen (PSA) levels [8,9]. In addition, the presence of DAC has been associated with significantly worse cancer-specific and overall survival [[10], [11], [12]].
In determining the prognostic significance of the presence of DAC, there are a number of difficulties with interpreting existing studies. Majority of studies reporting on clinical outcomes (such as metastases and cancer-specific survival) are registry based [3,10,11,13] and lack the granularity of clinicopathological data to control for potentially important confounders. On the other hand, smaller case-control series, while benefiting from centralised pathology review, invariably use the BCR as a clinical end-point [7,8]. The latter is particularly important as the BCR has been shown to be a poor surrogate marker for more relevant disease end-points such as metastasis and death, and as mentioned previously, progression of DAC in the absence of a detectable PSA has previously been described in the study by Orihuela and Green [9].
To address these deficiencies, we performed an international, multi-institutional study to describe the clinical and pathological characteristics of DAC, particularly focussing on the effect of presence of ductal variant cancer on metastasis-free survival. In selected cases, we then probed the genomic differences that may underlie the observed differences.
Section snippets
Patient selection
Patients with reported DAC on radical prostatectomy were retrospectively identified from a prospectively recorded pathology service database at TissuPath Specialist Pathology (Australia) and Oxford University Hospitals NHS Foundation Trust (United Kingdom) between January 2007 and June 2019. An independent comparative pure AAC cohort was additionally identified from a consecutive series of patients who underwent prostatectomies from Melbourne treated over the same time period. Clinical and
Results
We identified 207 DAC cases; of which, three were excluded for receiving neoadjuvant treatment and two were excluded for having distant metastases at the time of surgery. A total of 2351 cases were identified for a comparative AAC cohort; 39 and two patients were subsequently excluded for neoadjuvant treatment and distant metastases at the time of surgery, respectively. As the ductal cohort did not consist of any ISUP GG 1 pathologies, an additional 273 acinar ISUP GG 1 cases were excluded. The
Discussion
This study focuses on the clinicopathological outcomes of adenocarcinoma of the prostate with ductal variant pathology, and to our knowledge, this is the first large non-registry–based study to use metastasis-free survival as an end-point, an important clinical event in its own right and a more accurate surrogate marker for disease lethality than the more commonly used biochemical-free survival [23,24]. Consistent with previous reports, we have found that patients with DAC at prostatectomy have
Conclusion
In summary, DAC is more clinically aggressive than its acinar counterpart in terms of time to metastatic progression, despite having no significant difference in BCR-free survival. Preliminary investigation suggests that RB1 loss with associated increased cell proliferation and genomic instability may be a key molecular driver of these clinical differences.
Ethics approval and consent to participate
The study and collection of these data was institutionally reviewed and approved.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
Authors’ contribution
Ken Chow: Conceptualization, Data curation, Formal analysis, Methodology, Investigation, Project administration, Writing - original draft, Writing - review & editing. Justin Bedo: Data curation, Formal analysis, Methodology, Investigation, Writing - original draft, Writing - review & editing. Andrew Ryan: Formal analysis, Methodology, Investigation, Writing - review & editing. Dinesh Agarwal: Investigation, Writing - review & editing. Damien Bolton: Investigation, Writing - review & editing.
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
K.C. is supported by the Foundations for Surgery Research Scholarship from the Royal Australasian College of Surgeons, Postgraduate Medical Research Scholarship from the Prostate Cancer Research Fund and the Research Training Program Scholarship from the Australian Commonwealth Government. J.B. was supported by the Stafford Fox Medical Research Foundation. A.D.L. is funded by Cancer Research UK through a Clinician Scientist Fellowship (C57899/A25812). N.M.C. is supported by a Movember –
References (40)
- et al.
Contemporary population-based comparison of localized ductal adenocarcinoma and high-risk acinar adenocarcinoma of the prostate
Urology
(2015) - et al.
Prognostic significance of the proportion of ductal component in ductal adenocarcinoma of the prostate
J Urol
(2017) - et al.
Ductal prostate cancer: contemporary management and outcomes
Urol Oncol
(2008) - et al.
Ductal adenocarcinoma of the prostate: increased mortality risk and decreased serum prostate specific antigen
J Urol
(2010) - et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eur J Canc
(2009) - et al.
Integrative clinical genomics of advanced prostate cancer
Cell
(2015) Re: metastasis-free survival is a strong surrogate of overall survival in localized prostate cancer
Eur Urol
(2018)- et al.
Integrative genomic analysis of coincident cancer foci implicates CTNNB1 and PTEN alterations in ductal prostate cancer
Eur Urol Focus
(2019) - et al.
Compound genomic alterations of TP53, PTEN, and RB1 tumor suppressors in localized and metastatic prostate cancer
Eur Urol
(2019) - et al.
ABCB2 (TAP1) as the downstream target of SHH signaling enhances pancreatic ductal adenocarcinoma drug resistance
Canc Lett
(2013)
Systematic review links the prevalence of intraductal carcinoma of the prostate to prostate cancer risk categories
Eur Urol
Pathology and genetics of tumours of the urinary system and male genital organs
Pathologic stage of prostatic ductal adenocarcinoma at radical prostatectomy: effect of percentage of the ductal component and associated grade of acinar adenocarcinoma
Am J Surg Pathol
Histological variants of prostatic carcinoma and their significance
Histopathology
Endometrial (papillary) carcinoma of the prostatic utricle--response to orchiectomy. A case report
Cancer
Prostatic duct adenocarcinoma. Findings at radical prostatectomy
Cancer
Histopathological features of ductal adenocarcinoma of the prostate in 1,051 radical prostatectomy specimens
Virchows Arch
Prognostic values of clinicopathological characteristics and survival outcomes in prostate infiltrating ductal carcinoma: a population-based study
Oncotarget
Incidence and outcomes of ductal carcinoma of the prostate in the USA: analysis of data from the Surveillance, Epidemiology, and End Results program
BJU Int
Immunohistochemical verification of ductal differentiation in prostate cancer
APMIS
Cited by (12)
The rising incidence of ductal adenocarcinoma and intraductal carcinoma of the prostate: Diagnostic accuracy of biopsy, MRI-visibility, and outcomes
2023, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :IDC has also been reported to be associated with distant metastasis at the time of initial clinical recurrence [21]. Similarly, DA histology has been associated with worse BCR, salvage therapy free survival, and metastasis free survival [22,23]. However, in one study evaluating BCR after RP controlling for tumor grade, stage, and margin status, neither DA nor IDC were independent predictors of BCR suggesting they may be associated with adverse features without exerting independent prognostic value [24].
What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?
2023, Pflugers Archiv European Journal of PhysiologyA novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer
2023, Journal of Zhejiang University: Science B