Beyond the Abstract - Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy, by Theo Van der Kwast, Najla Al Daoud, and Robert G. Bristow

BERKELEY, CA (UroToday.com) - Many clinicians lack familiarity with the diagnosis of intraductal carcinoma of the prostate.

They may confuse intraductal carcinoma of the prostate with ductal adenocarcinoma (previously known as endometrioid carcinoma) and with high-grade prostatic intra-epithelial neoplasia (PIN). Intraductal carcinoma of the prostate is a morphologically distinct entity, characterized by a distension of prostatic ducts and glands most commonly by a cribriform mass of dysplastic cells. Some basal cells at the well-delineated peripheral rim surrounding these cribriform tumour areas must be present to distinguish intraductal from invasive cribriform prostate cancer. Morphologically, these prostate lesions show a high resemblance with ductal carcinoma in situ of the breast, hence their label “intraductal carcinoma.”¹On the other hand, ductal adenocarcinoma of the prostate is a high-grade variant of prostatic adenocarcinoma often associated with a conventional acinar adenocarcinoma component. Adding to the confusion, ductal adenocarcinoma is commonly associated with intraductal carcinoma. High grade PIN is considered a precursor of prostatic adenocarcinoma, whereas intraductal carcinoma is most commonly thought to represent the intra-ductal propagation and spread of the associated prostate cancer. The rare occurrence of intraductal carcinoma of the prostate in the absence of an invasive carcinoma component has dispelled doubt about this view. 

Intraductal carcinoma of the prostate may occur as an isolated finding in prostate biopsies, but this is rare, and most commonly intraductal carcinoma is found in association with a conventional prostatic adenocarcinoma. When intraductal carcinoma of the prostate is encountered as an isolated finding, in about 80% of the cases a prostatectomy will reveal an invasive adenocarcinoma, often with unfavourable features.² Thus, it is clinically important to distinguish isolated intraductal carcinoma of the prostate from high grade PIN, since the latter lesion has a rather limited clinical significance. In the case of an unequivocal biopsy diagnosis of isolated intraductal carcinoma of the prostate, most experts feel that immediate definite treatment is warranted, or alternatively early repeat biopsies to establish the presence of invasive adenocarcinoma. A summary of the most pertinent differences between the three prostate lesions are listed in the table below.

A few papers have demonstrated that presence of intraductal carcinoma of the prostate in association with conventional adenocarcinoma in a prostatectomy conveys an unfavourable prognosis and represents an independent prognosticator for early biochemical recurrence.³ We estimate that in about 20% of the prostatectomy specimens, intraductal carcinoma of the prostate can be identified, mostly in the vicinity of the adenocarcinoma. Its presence is associated with Gleason score ≥7 (4 +3) adenocarcinoma and extraprostatic spread. We studied the frequency and prognostic impact of intraductal carcinoma of the prostate in diagnostic specimens (biopsies and transurethral resections of the prostate) of patients with intermediate (Toronto radiotherapy cohort) and high-risk prostate cancer (EORTC trial 22863) who subsequently were treated by radiotherapy and long term androgen deprivation.⁴ We noted that intraductal carcinoma of the prostate could be seen in about 20% of the specimens. In both cohorts, presence of intraductal carcinoma was a strong prognosticator for early biochemical recurrence, and in the EORTC cohort with a longer follow-up also its association with clinical recurrence and metastatic disease was shown. Ongoing genetic studies, including whole genome sequencing of IDC+ and IDC- tumours of the same Gleason grade, as is being completed in the Canadian Prostate Cancer Genome Network (CPC-GENE), will no doubt shed further light on the genetic alterations of IDC + tumours. This prognostic impact was independent of the Gleason score and therefore, we recommend the routine reporting of intraductal carcinoma of the prostate whenever identified in a prostate biopsy.

References:

1. Pickup M, Van der Kwast TH. My approach to intraductal lesions of the prostate gland. J Clin Pathol 2007;60:856-65.
2. Robinson BD, Epstein JI. Intraductal carcinoma of the prostate without invasive carcinoma on needle biopsy: emphasis on radical prostatectomy findings. J Urol 2010;184:1328-33.
3. Cohen R, Chan W, Edgar S, Robinson E, Dodd N, Hoscek S, Mundy IP. Prediction of pathologic stage and clinical outcome in prostate cancer; an improved pre-operative sequential model incorporating biopsy determined intraductal carcinoma. Br J Urol 1998;81:413-18.
4. Van der Kwast T, Al Daoud N, Collette L, Sykes J, Thoms J, Milosevic M, Bristow RG, Van Tienhoven G, Warde P, Mirimanoff RO, Bolla M. Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy. Eur J Cancer 2012;48:1318-25.

Written by:
Theo Van der Kwast,^a Najla Al Daoud,^b and Robert G Bristow^c 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. 

1. Dept. of Pathology, University Health Network, Toronto, Canada
2. Dept. of Pathology and Microbiology , Jordan University of Science and Technology, Irbid, Jordan
3. Dept. of Radiation Oncology, Princess Margaret Hospital, Toronto, Canada

Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy - Abstract

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