CUA 2017: Intraductal Prostate Cancer: Marker of Aggressive Disease?

Toronto, Ontario ( Dr. Van der Kwast, a recognized uro-pathologist from the Princess Margaret Cancer Centre (PMCC), gave an excellent talk regarding the clinical implications of finding intraductal prostate cancer (IPC) and cribriform pattern on prostate pathology (radical prostatectomy or prostate biopsy). 

First, what is intraductal carcinoma (IDC)? IDC is a distension of antecedent prostate ducts and glands by neoplastic cells / luminal spanning. Importantly, there is no invasion! Basal cells persist, so this may provide confusion to clinicians. However, the importance of the IDC finding cannot be understated.
  • It is not HG PIN – though previously used to be called HG PIN on pathology results.
  • It is not ductal adenocarcinoma (endometroid carcinoma) 
IDC is not a new pathologic finding, though it has developed a resurgence. The original series of papers between 1996-2000 focused on the finding of IDC in radical prostatectomy specimens. Its finding was associated with large tumor volumes, high Gleason scores, increased risk of extraprostatic extension and worse clinical outcomes.

More recent studies in the past decade have identified IDC in prostate biopsies and have found that it is associated with advanced stage at the time of prostatectomy, is an independent predictor of early biochemical recurrence (BCR) and metastatic disease after radiotherapy, and is the only independent prognostic for death of disease in patients presenting with metastatic prostate cancer. Importantly, isolated IDC in the absence of invasive disease is predictive of advanced stage cancer and risk of metastatic disease. 

Cribriform pattern is a subset of grade 4 histology patterns – but not all Gleason 4 is equal. Cribriform is clearly a more aggressive subset of Gleason 4 histology. While IDC is more recognized for its poor prognostic features, cribriform pattern is gaining more recognition. It is associated with non-organ-confined prostate cancer and its presence in RP specimens is an independent predictor of BCR, metastatic disease and death. IDC and cribriform pattern often colocalize, though. Indeed, combining IDC and cribriform was more prognostic of BCR and metastatic disease in a radiotherapy-treated cohort of intermediate risk prostate cancer than either alone. 

There is molecular rationale for this clinical correlation. In a study that looked at genetic differences between IDC/Cribriform patients vs. those without, a single long non-coding RNA (lncRNA) was identified as over-expressed – SChLAP1. Interestingly, in older studies, SChLAP1 was already identified as a marker of metastatic progression in prostate cancer; potentially identifying patients with IDC/cribriform histology. IDC is also a feature of BRCA2 carrier associated prostate cancers, underlying its more aggressive natural history.

In an interesting study recently published,1 IDC or cribriform pattern actually outperformed % Gleason score 4 as a predictor of time to BCR in patients with Gleason 3+4=7 intermediate risk prostate cancer. 

Take Home Points:
1. IDC and Cribriform architecture are independent prognostic features of BCR, metastases and disease-specific survival after prostatectomy and radiotherapy
2. IDC and CA can be combined into a more potent prognostic index
3. IDC and CA are distinct at the molecular-genetic level 
4. IDC and CA in Gleason 6 and Gleason 3+4=7 prostate cancer can be used as a determinant of clinically significant prostate cancer
5. Routine reporting of both is recommended as it may affect clinical decision making

Presented By: Theo Van der Kwast, MD, PhD, FRCPC, University of Toronto

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto  Twitter: @tchandra_uromd at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada

1. Kweldam CF et al. Presence of invasive cribriform or intraductal growth at biopsy outperforms percentage grade 4 in predicting outcome of Gleason score 3+4=7 prostate cancer. Mod Pathol. 2017 May 19. doi: 10.1038/modpathol.2017.29. [Epub ahead of print]