SUO 2021: Adverse Prostate Cancer Pathological Variants: Considerations for Management

( In a plenary session at the Society of Urologic Oncology Annual Meeting focused on early prostate cancer diagnosis and treatment, Dr. Jennifer Gordetsky discussed pathological variants of prostate cancer and their influence on treatment.

She first began by discussing the importance of the amount of pattern four disease among patients with grade group 2 (Gleason score 3+4). She began by emphasizing that, while cribriform glands were initially classified by Dr. Gleason as pattern 3, as of 214, all cribriform glands are now considered pattern 4.

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The importance of efforts to categorize grade groups, as Dr. Gordetsky highlighted, arises from the acknowledgment that the behaviour of Gleason 7 tumors diffed substantially on the basis of whether pattern 3 or pattern 4 is dominant. In the context of grade group 2 tumors, she emphasized the importance of risk stratification as some of these men may be suitable for surveillance whereas active treatment is likely most appropriate for others. To this end, she emphasized two key pathologic characteristics:

1. The proportion of pattern 4 disease

2. The type of pattern 4 diseases (cribriform, poorly formed glands, fused glands, glomeruloid)

Citing a prior systematic review, Dr. Gordetsky emphasized that the percentage of Gleason pattern 4 disease at the time of prostate biopsy or radical prostatectomy was independently predictive of adverse pathology on radical prostatectomy, biochemical recurrence, and cancer-specific survival. However, she emphasized that these studies typically did not account for the type of morphology.

Dr. Gordetsky then discussed the prognostic importance of histological variants including the presence of invasive cribriform prostate cancer and intraductal carcinoma of the prostate. These pathological variants as independently associated with biochemical-recurrence-free survival, high-grade disease at the time of radical prostatectomy, and higher stage disease at the time of radical prostatectomy. Additionally, the presence of cribriform cancer outperforms the percentage of Gleason pattern 4 and tertiary pattern 5 in predicting outcomes among patients with grade group 2 disease.

She further highlighted that there are many unanswered questions including the effect of these histologic variants on therapeutic resistance, the association with germline mutations in DNA repair genes, sampling, and underdiagnosis on prostate biopsy, interobserver variability and reporting, and the issue of aggregating cribriform and intraductal histologies in studies to date.

Presented by: Jennifer B. Gordetsky, MD, Professor, Departments of Pathology and Urology, Vanderbilt University Medical Center

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 Society of Urologic Oncology (SUO) Winter Annual Meeting, Orlando, FL, Wed, Dec 1 – Fri, Dec 3, 2021. 

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