Intraductal carcinoma of the prostate: precursor or aggressive phenotype of prostate cancer?

BACKGROUND Although the term "intraductal carcinoma of the prostate" (IDC-P) was introduced almost 40 years ago, there is still the 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). METHODS Recent data obtained from histological, molecular, and clinical studies were reviewed 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). RESULTS HGPIN is the only accepted precursor of PCa. Its diagnosis in prostate biopsies has no prognostic implications, and does not dictate therapeutic decisions. By contrast, IDC-P correlates with a worse pathological and clinical outcome. IDC-P differs from HGPIN by distinct histological and molecular features. Recent clinical studies report that IDC-P is associated with neoadjuvant androgen deprivation therapy (ADT) and, chemotherapy (CT) failure as well as early disease recurrence after external beam radiation. Finally, IDC-P is associated with TMPRSS2-ERG gene fusion, which was reported to be regulated by estrogens and their receptors. CONCLUSIONS IDC-P is an aggressive phenotype of prostate cancer and predicts poor response to ADT, CT, and external beam radiation. IDC-P should be separated from HGPIN and should be reported in prostate biopsies and prostatectomy specimens.