New Canadian study below.
It's all very well for Dr. Myers - speaking of overtreatment - to say :"Don't call it cancer" when the Gleason score is 3+3, but 25-30% of such men will progress while on Active Surveillance [AS]. In some cases, a delay in treatment might worsen the outcome.
It isn't as though there aren't tests that might identify those men. & now there is another potential test:
"We demonstrate that a urine-based Classifier Panel of four methylation biomarkers predicts disease progression of AS patients."
Methyl is important for preventing cancer. Low levels (hypomethylation) cause DNA instability. However, when PCa exists, the cells tend to become hypermethylated, & the DNA promoter regions for tumor suppressor genes become methylated (silenced).
The main dietary methyl donor is folate, & methyl intake could be restricted by cutting back on leafy greens. But in countries where grains have been fortified with folic acid (a synthetic substitute for folate), it can be difficult to restrict methyl intake.
Vitamin B12 is a cofactor in methyl processing & one could restrict that.
If methyl is plentiful, aggressive PCa cells will load up on it. If intake is restricted, the Canadian test will be less useful - but restriction will also make the cancer less aggressive.
J Urol. 2016 Aug 18. pii: S0022-5347(16)31067-9. doi: 10.1016/j.juro.2016.08.081. [Epub ahead of print]
Urinary DNA methylation biomarkers for non-invasive prediction of aggressive disease in prostate cancer patients on Active Surveillance.
Zhao F1, Olkhov-Mitsel E1, van der Kwast T2, Sykes J3, Zdravic D4, Venkateswaran V5, Zlotta AR6, Loblaw A7, Fleshner NE8, Klotz L5, Vesprini D7, Bapat B9.
Prostate cancer (PCa) patients on active surveillance (AS) are monitored through repeated prostate-specific antigen (PSA) measurements, digital rectal exams (DREs) and prostate biopsies. A subset of AS patients will later "reclassify" with disease progression prompting definitive treatment. To minimize the risk of under-treating such AS patients, minimally-invasive tests incorporating biomarkers to identify patients who will reclassify are urgently needed.
We assessed post-DRE urine samples of AS patients for selected DNA methylation biomarkers that were previously investigated in radical prostatectomy specimens and shown to correlate with increasing risk of PCa. Post-DRE urine samples were prospectively collected from 153 men on AS who were diagnosed with Gleason Score (GS) 6 disease. Urinary sediment DNA was analyzed for eight DNA methylation biomarkers by multiplex MethyLight assay. Correlative analyses were performed on gene methylation and clinicopathological variables to test their predictive ability of patient risk-reclassification.
Using backward logistic regression, a four gene methylation "Classifier Panel"(APC, CRIP3, GSTP1, HOXD8) was identified. The Classifier Panel was able to predict patient reclassification (OR= 2.559; 95% CI= 1.257-5.212). We observed this panel to be an independent and superior predictor compared to current clinical predictors such as PSA at diagnosis or % of tumor positive cores in initial biopsy.
We demonstrate that a urine-based Classifier Panel of four methylation biomarkers predicts disease progression of AS patients. Once validated in independent AS cohorts, these promising biomarkers may help establish a less-invasive method for monitoring patients on AS programs.
Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
Active surveillance; Biomarkers; DNA methylation; Prostate cancer; Risk-reclassification; Word Count
PMID: 27545574 DOI: 10.1016/j.juro.2016.08.081
[PubMed - as supplied by publisher]