Cancer biomarkers: Key tools in diagnosis and treatment

Urine-Based Biomarker Test Detects Clinically Significant Prostate ...

The urinary 18-gene MyProstateScore 2.0 (MPS2) test can detect clinically significant prostate cancer and reduce the frequency of biopsies compared with the Prostate Cancer Prevention Trial risk calculator (PCPTrc), investigators report.

"The MyProstateScore 2.0 test measures 18 cancer-associated and high-grade cancer-associated genes in urine to provide a percentage likelihood of detecting GG ≥ 2 cancer on biopsy," Jeffrey J. Tosoian, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues explained in The Journal of Urology.

"Using urine obtained without [digital rectal exam (DRE)], the MPS2 test provides a highly accurate, personalized risk score to better identify patients who can confidently forego additional testing with MRI or biopsy."

The team previously validated the test using post-DRE urine. In the current study, they tested MPS2 as a first-line noninvasive test after serum PSA screening using first-catch, non-DRE urine. They tested 3 MPS2-based models: biomarkers alone (1), biomarkers and clinical data including, age, race, PSA, DRE findings, family history, and prior negative biopsy (2), and biomarkers combined with clinical factors and prostate volume (3).

Among 266 men with a median PSA of 6.6 ng/mL, grade group 2 or higher cancer was eventually diagnosed in 103 men (39%), including 83, 9, and 11 men with GG2, GG3, and GG4-5 disease, respectively. Median MPS2 values were significantly higher in patients with vs without GG 2 or higher cancer in model 1 (31% vs 15%), model 2 (36% vs 15%), and model 3 (41% vs 13%), Dr Tosoian's team reported. MRI use did not differ between groups with and without GG 2 or higher cancer: 18% vs 17%.

The MPS2 models outperformed PSA alone and the PCPT risk calculator, they added. The area under the curve (AUC) for the 3 MPS2 models was 71%, 74%, and 77%, respectively, compared with 57% for PSA and 62% for the PCPT risk calculator. Only MPS2 model 1 was not significantly better than the PCPTrc. Model 3 appeared the most discriminative.

Assuming a 92% rate of detecting clinically relevant prostate cancers at initial biopsy, use of MPS2 would have avoided 36% to 42% of unnecessary biopsies, as compared with 13% using the PCPTrc, the investigators reported. In the repeat biopsy setting, MPS2 would have avoided 44% to 53% of unnecessary biopsies, compared with only 2.6% using the PCPTrc, Dr Tosoian's team reported. Systematic biopsy with or without prebiopsy MRI was the reference standard for prostate cancer diagnosis, which is a study limitation.

"Ultimately, the MPS2 tool's superior sensitivity and positive predictive value better stratify patients for invasive confirmatory testing, while sparing those without significant clinical risk," Shreya Thiagarajan and coauthors at Dell Medical School at the University of Texas at Austin wrote in an accompanying editorial.

The team will be investigating MPS2 use in patients undergoing active surveillance for low-grade prostate cancer. If further validated, the MPS2 might enable at-home testing for clinically significant prostate cancer, which would especially benefit remote patients relying on telehealth care.

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