Urine Test for Prostate Cancer Signals Amount of Aggressive Tumor

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that more cases of Gleason pattern 4 cancer are associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of Norwich Medical School, University of East Anglia, in the United Kingdom. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease,” he said.

The study by Clark and colleagues was published online on November 3 in Life.

Tests using the traditional blood-based biomarker for prostate cancer — prostate-specific antigen (PSA) — have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Clark and his colleagues explain. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason Pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors write.

The researchers also examined radical-prostatectomy specimens from nine men — three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumor showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Clark told Medscape Medical News. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center, in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told Medscape Medical News by email. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit ― the men do not have to come to a hospital to provide a urine sample,” Clark said.

Life. Published online November 3, 2021. Full text

The study did not receive commercial funding. Clark and two of his coauthors have filed a patent application related to their research.

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