Should Gleason 6 be labeled as cancer?
(2016, Full Text, Dr. J. Epstein is a co-author)
The case for removing the label of cancer is largely supported by the following: i) the negligible rate of lymph node metastases in men with GS6 disease in RPs; ii) the very low risk of progression after primary treatment in men with GS6 disease; iii) the general safety of AS and the very low rates of progression of men with GS6 disease in AS; and iv) the lack of convincing molecular pathological longitudinal evidence to date showing that a pure GS6 tumor can progress to a higher grade life threatening lesion over time. In our opinion, however, the arguments for the continuation of using the term cancer for these lesions still overshadow those against removing the label of cancer. For example, there are a number of histological and molecular features of GS6 tumors that support the label of cancer for these lesions and there is no solid molecular evidence suggesting that GS6 vs higher grade tumors commonly arise as unique and distinct molecular subtypes as in the case in other cancers such those in the breast and urinary bladder. In fact, a number of histopathological and molecular alterations are shared between GS6 and higher grade lesions such as nuclear alterations, invasion into the stroma, ETS family member gene fusion events, chromoplexy and somatic CpG hypermethylation of specific genes. While some of these changes are substantially less common in GS6 tumors, they nonetheless support similar pathways of tumor development overall. Further, given the practical issues with sampling leading to frequent under-grading with prostate needle biopsies, we submit that it would be pre-mature to remove the label of cancer from GS6 prostate tumors. Rather, we favor the application of new prognostic groups such that GS6 tumors fall into the lowest of these groups which will provide patients and clinicians with reassurance about the overall favorable prognosis of these tumors, without renaming the lesion to a non-cancerous entity at this time (3, 14).
The case to be made that pure Gleason score 6 (i.e. only Gleason pattern 3) tumors are not capable of causing significant harm in the vast majority of cases.
Yet, the issue of Gleason score 6 (pattern 3 only) lesions identified by today’s standard prostate needle biopsies to be associated with un-sampled higher grade tumor in up to 35% of cases greatly diminishes the force of the argument for removing the cancer label.
Further support for retaining the cancer label stems from molecular studies of heritable somatic genomic alterations (e.g. GSTP1 promoter hypermethylation, TMPRSS2-ERG fusion genes and chromoplexy) that suggest common molecular pathways for early lesion develop in Gleason pattern 3 and higher grade lesions."
--------------------------------------------------------------------------------------------------"Is This Really Cancer? — Movement builds to classify Gleason 6 prostate lesions as nonmalignant"
'He [Dr. L Klotz] said about
2% of patients with low-grade Gleason 6 have serious genetic aberrations in their cancer cells, suggesting the cancers may be more aggressive. "It's a small proportion but it's not zero," he said. These cells probably mutate to a higher Gleason pattern before they metastasize.'
(1) As mentioned, as many as 35% of men who have a G6 biopsy are upgraded if they choose surgery because they harbor lesions >G6. In other words, they do
have cancer even if you don't label G6 as such.
(2) Even among men who would have true
G6 disease (that would be confirmed if they choose surgery) about
10% of them are nonetheless high risk for developing higher-grade lesions and mets within 5 years according to Decipher test results.
(3) Complacency and lax or no AS would likely increase among men who think "This isn't cancer--now I don't have to worry."
The correction for overtreating G6 is education (of doctors and patients) and proper AS, not redefining G6.
Post Edited (DjinTonic) : 4/20/2022 8:07:39 PM (GMT-6)