The issue of selection criteria and reclassification in active surveillance for prostate cancer patients from the view point of pathology was the focus in the second segment at EMUC17 with an update lecture by Prof. Jonathan Epstein (US).
Epstein (US) discussed several AS issues in his lecture titled “Is there a shift for selection criteria and definition of reclassification for prostate cancer on active surveillance?”. He covered topics such as the criteria for selection for active surveillance (AS), follow-up for men on AS, trigger for intervention on AS, and the changes in reporting grade for AS.
Among the current criteria he mentioned are age (life expectancy or follow-up time), patient preference, cancer extent (clinical stage), needle biopsy findings (grade, extent), and PSA criteria such as PSA and density.
According to Epstein, the pre-operative model to predict insignificant cancer included the following: stage T1c (non-palpable), Gleason score 6, <3 cores involved by cancer, no core with >50% involvement and PSA density (PSA/gland weight) < 0.15.
Epstein also underlined the importance of distinguishing between very low (factors in extent of cancer on biopsy) and low risk disease.
He said cancer extent on biopsy and PSA density at diagnosis are directly associated with grade reclassification during surveillance (Loeb et al. J Urology 2013), there is a two-fold higher risk of surgically confirmed non-organ confined cancer and Gleason pattern 4 in men with low risk versus very low risk disease (Tosolan et al. J. Urol 2013), and there is a two-fold higher risk of metastatic disease, prostate cancer death, and treatment failure with surveillance for low-risk versus very low risk disease (as shown by Godtman el, Eur Urol 2016).
Epstein also discussed the advantage of unilateral versus less than 50% maximum cancer per core, and the issues of variable inclusion criteria for reclassification. He also pointed out the practical use of a risk calculator.
“Sixty percent of our cohort had a predicted probability of grade reclassification of <20% with a false negative rate of <10%,” said Epstein adding that doctors can “reassure patients that they have a high probability of successfully staying on AS and can space out the repeat biopsies.”
Fully informed patient
Epstein also highlighted the need for doctors, particularly those with patients who have Gleason 3+4, to provide full information.
“Men with Gleason score 3+4=7 on biopsy who are otherwise eligible for curative intervention should be fully informed as to the avoidable risk associated with AS,” he said. He then mentioned novel markers and imaging which may be useful in surveillance such as urinary markers (PCa3/TMPRSS2:ERG), serum markers, molecular tissue-based markers and multi-parametric MRI/image-guided biopsy.
Another issue he noted are the problems with the Gleason system with regards scale.
“Six is the lowest grade reported although the scale goes from 2-10,” he said. “Thus, patients are told they have a Gleason score of 6 out of 10, and logically but incorrectly think that they have a tumor in the middle of the grade spectrum, contributing to the fear of cancer.”’
He added: “Urologists need to reassure and educate patients when told they have Gleason score 6 cancer. At the same time there is the need to modify how pathologists report cancer grade to more accurately reflect their behaviour.”
He said there is a new grading system that was recently accepted in the 2016 WHO Pathology & Genetics together with the College of American Pathologists (CAP) as reflected in the AJCC Cancer Staging Manual-TNM System (8th Edition).
“Starting in January 2018, it will be mandatory for pathology laboratories accredited by CAP to use the new grading system in parallel to the Gleason grading system and to report percent pattern 4 for Gleason score 3+4=7,” said Epstein.