A urine test can assess intermediate prostate cancer risk without biopsy through the amount of Gleason pattern-4 biomarker, to potentially minimise over-diagnosis and over-treatment, found a pilot study in the MDPI Journal.
Prostate cancer is the most common cancer in men in the UK. It usually develops slowly and most cancers will not require treatment in a man’s lifetime. The most common means to diagnose it include blood tests, a digital rectal examination (DRE), an MRI scan and an invasive biopsy.
However, doctors usually struggle to predict which tumours will progress to a more aggressive form, making it hard to decide on treatment for many men.
Now, researchers at the University of East Anglia (UEA) have shown that a prostate cancer urine test can identify men at intermediate risk”who can then safely avoid immediate treatment and benefit from active surveillance instead.
The study reveals how urine biomarkers can show the amount of significant cancer in a prostate, highlighting with more certainty which men need treatment.
Previously, the team’s Prostate Urine Risk (PUR) test could identify men with high and low risk cancers. But thanks to some fine-tuning, it can now help men with intermediate-risk disease, for whom treatment options had been less clear.
Lead researcher Dr Jeremy Clark, from UEA’s Norwich Medical School, said: “While prostate cancer is responsible for a large proportion of all male cancer deaths, it is more commonly a disease men die with, rather than from.
“Therefore, there is a desperate need for improvements in diagnosing and predicting outcomes for prostate cancer patients to minimise over-diagnosis and over-treatment while appropriately treating men with aggressive disease, especially if this can be done without taking an invasive biopsy.
“We developed the Prostate Urine Risk Test, or PUR for short, the ‘risk’ here referring to the aggressiveness of the cancer and its potential to spread to other organs, which would eventually kill the patient. But prostate cancer is very complex and risk levels vary widely between men.
“Previously we have shown that PUR can identify men with high-risk cancer, which requires immediate treatment, and also low-risk cancer, which has a very low rate of progression and does not generally need treatment.
“But there is a third category of men with “intermediate-risk”, which falls in between these extremes. Around half of men diagnosed with prostate cancer fall into this group and the treatment pathways for them have been less clear, until now.
“It is known that disease progression in intermediate-risk men is associated with the presence of increasing amounts of Gleason pattern 4 cancer in their prostate. Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy.
“So not only can PUR measure the presence of aggressive cancer, but it can also measure increasing amounts of aggressive cancer in a prostate.
“This means it can show us which men at intermediate risk may require treatment and which may, instead, be managed conservatively with surveillance. PUR will also be useful for monitoring disease in men who don’t currently require treatment, and flag up the emergence and expansion of aggressive disease,” he added.
The results of this pilot study will be further investigated in a much larger cohort of men using samples collected with a prostate screening box that the patients receive by mail and return samples by post directly for analysis at UEA.
Dr Sarah Hsiao, director, Biomedical Research and Impact at Movember (one of the study funders), said: “This research shows that the PUR test can be used to estimate the level of a specific pathological characteristic (Gleason Pattern 4) that is linked to increased risk of disease progression in men with prostate cancer. It’s important because for men whose prostate tumour contains varying levels of Gleason Pattern 4, a prostate biopsy is necessary to determine whether they should receive active treatment or be managed by active surveillance.
“We look forward to seeing further validation of this research in a larger study cohort. If successful, this non-invasive PUR test may be able to support decision-making process without needing an invasive prostate biopsy that is associated with discomfort and risk of infection.”
Study details
The Urine Biomarker PUR-4 Is Positively Associated with the Amount of Gleason 4 in Human Prostate Cancers
Richard Y. Ball, Ryan Cardenas, Mark Winterbone, MArcelino Hanna, Chris Parker, Rachel Hurst, Daniel Brewer, Lauren D’Sa, Rob Mills, Colin Cooper, Jeremy Clark.
Published in MDPI Journal on 3 November 2021
Abstract
The Prostate Urine Risk (PUR) biomarker is a four-group classifier for predicting outcome in patients prior to biopsy and for men on active surveillance. The four categories correspond to the probabilities of the presence of normal tissue (PUR-1), D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer. In the current study we investigate how the PUR-4 status is linked to Gleason grade, prostate volume, and tumor volume as assessed from biopsy (n = 215) and prostatectomy (n = 9) samples. For biopsy data PUR-4 status alone was linked to Gleason Grade group (GG) (Spearman’s, ρ = 0.58, p < 0.001 trend). To assess the impact of tumor volume each GG was dichotomized into Small and Large volume cancers relative to median volume. For GG1 (Gleason Pattern 3 + 3) cancers volume had no impact on PUR-4 status. In contrast for GG2 (3 + 4) and GG3 (4 + 3) cancers PUR-4 levels increased in large volume cancers with statistical significance observed for GG2 (p = 0.005; Games-Howell). These data indicated that PUR-4 status is linked to the presence of Gleason Pattern 4. To test this observation tumor burden and Gleason Pattern were assessed in nine surgically removed and sectioned prostates allowing reconstruction of 3D maps. PUR-4 was not correlated with Gleason Pattern 3 amount, total tumor volume or prostate size. A strong correlation was observed between amount of Gleason Pattern 4 tumor and PUR-4 signature (r = 0.71, p = 0.034, Pearson’s). These observations shed light on the biological significance of the PUR biomarker and support its use as a non-invasive means of assessing the presence of clinically significant prostate cancer.
Conclusions
A strong association was observed between an increasing amount of Gleason pattern 4 cancer and increasing PUR-4 signal. These data suggest that the PUR-4 signature could provide useful additional information in determining the amount of clinically significant tumour within a prostate and thereby help guide the patient treatment pathway with essential information for triage, improved management and prognostic utility.
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