BERKELEY, CA (UroToday.com) - Although detailed morphological and clinical correlations of intraductal carcinoma of the prostate (IDC-P) were provided by McNeal and Yemoto in 1997, there is still a lack of appreciation that this entity represents a clinically aggressive disease that continues to be misreported under the diagnostic category of high-grade prostatic intraepithelial neoplasia (HGPIN). Since the introduction of this term by Bostwick and Brawer in 1987, all intraductal neoplastic lesions of prostatic origin, including IDC-P, fall under the unifying category of HGPIN. As a consequence, the diagnosis of IDC-P is frequently not reported, as many pathologists summarize these intraductal malignancies under the diagnostic category of HGPIN.
The purpose of the current review is to demonstrate that IDC-P significantly differs from HGPIN, and has a major impact in terms of diagnosis, prognosis and therapy of prostate cancer (PCa).
A series of morphological criteria have been evaluated by different authors who differentiate between IDC-P and HGPIN. Recent molecular data suggest that HGPIN and IDC-P are distinct intraductal lesions, where HGPIN is a precursor, and IDC-P an aggressive phenotype of PCa. Clinical studies have identified IDC-P as an independently significant variable in the prediction of poor clinical outcome, and treatment failure. Particularly, the diagnosis of IDC-P predicts poor response to neoadjuvant chemotherapy, androgen deprivation therapy, and external beam radiation. In a recent study enrolling 118 intermediate-, and 132 high-risk PCa patients, the presence of IDC-P in prostate biopsies was identified as an independent prognosticator of early biochemical relapse (< 36 months) and metastatic failure after external beam radiotherapy. It is noteworthy that IDC-P is associated with TMPRSS2- ERG gene fusion, which was reported to be regulated by estrogens and their receptors. In fact, IDC-P and related Gleason pattern 4/5 PCa may express the estrogen receptor alpha (ERα) and the estrogen inducible progesterone receptor (PR), indicating that these tumors are regulated by estrogens and could be targeted accordingly.
Separating IDC-P from HGPIN has several clinical implications. In fact, the diagnosis of HGPIN in prostate biopsies does not dictate therapeutic decisions and has no prognostic implications in terms of PSA recurrence after prostatectomy. By contrast, the presence of IDC-P in prostate biopsies is frequently associated with high-grade cancer and poor prognostic parameters at radical prostatectomy as well as advanced disease following other therapies. The incidence of IDC-P in prostatectomy specimens depends on tumor volume. In the series of John McNeal, IDC-P was observed in 10% of cases with tumor volume less than 2 ccm, 28% in tumors between 2 and 4 cm3, and 47% in tumors larger than 4 cm3. Given the prognostic impact of IDC-P, a Gleason grade should be assigned for each IDC-P and incorporated in the Gleason score both in biopsies and in prostatectomy specimens. In general, the various growth patterns of IDC-P fall into the Gleason pattern 4/5 categories based on the 2005 modified Gleason grading. A new postoperative nomogram incorporates IDC-P as a variable, and may enhance prediction. Furthermore, IDC-P has been associated with neoadjuvant androgen deprivation therapy (ADT) and chemotherapy (CT) failure, as well as early disease recurrence after external beam radiation. In the presence of IDC-P in prostate biopsies, radical prostatectomy combined with extended lymphadenectomy may be more effective in improving survival than radiotherapy. Another feature of IDC-P refers to the TMPRSS2- ERG gene fusion, which is regulated by estrogens and their receptors. Pharmacological inhibition of TMPRSS2- ERG gene fusion IDC-P using drugs that antagonize ERα and PR activity may hold promise as new therapeutic strategy for this aggressive subtype of PCa. However, this issue warrants further evaluation in clinical studies.
In summary, current histopathological, molecular and clinical characteristics identify IDC-P as an aggressive phenotype of PCa, and clearly separate this entity from HGPIN, which is accepted by most of urologists and pathologists as a facultative precursor of PCa. The diagnosis of IDC-P on prostate biopsy predicts high-grade cancer and poor prognostic parameters at radical prostatectomy, and poor response to neoadjuvant ADT, CT, and external beam radiation. Reporting IDC-P in prostate biopsies and prostatectomy specimens has a major impact in terms of diagnosis, prognosis, and therapy of prostate cancer.
Written by:
Helmut Bonkhoff, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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Intraductal carcinoma of the prostate: Precursor or aggressive phenotype of prostate cancer? - Abstract
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