Combined urinary testing for PCA3 and TMPRSS2:ERG (T2:ERG) RNA can help avoid unnecessary biopsies while maintaining ability to detect aggressive prostate cancer, according to a new study.
“Strategies are needed for detecting cancers with more aggressive features (Gleason score, ≥ 7) to enable survival benefits from treatment while limiting unnecessary biopsies and overdetection of indolent disease,” wrote study authors led by Martin G. Sanda, MD, of the department of urology at Emory University School of Medicine in Atlanta. “Gene expression alterations in prostate cancer representing an opportunity to refine early detection include overexpression of PCA3, a noncoding RNA, and aberrant T2:ERG expression.”
This study evaluated whether using urinary testing of those markers could improve specificity for detecting aggressive prostate cancer. It included a developmental cohort of 516 men presenting for first-time prostate biopsy, and 561 men in a validation cohort; both cohorts had a mean age of 62 years. The results were published in JAMA Oncology.
In the developmental cohort, prostate-specific antigen (PSA) testing alone had a specificity for aggressive prostate cancer of 18%, at a 95% sensitivity; combining urinary T2:ERG and PCA3 testing improved that specificity to 39%, while maintaining sensitivity. The validation cohort confirmed this, with specificity improving from 17% to 33% (P = .04), while maintaining a sensitivity of 93%.
If biopsies were restricted to men in the validation cohort with positive urinary findings or a PSA above 10 ng/mL, this would have avoided 42% of unnecessary biopsies, the authors wrote. It would also have avoided overdetection of 12% of indolent cancers. Combining these tests in optimized fashion—whereby high expression of either urinary marker prompts a prostate biopsy—could avoid 33% of “excessive” prostate biopsies. A cost-benefit analysis also suggested that using this testing algorithm could improve value specifically in younger men.
The authors noted that because this study was done in men presenting for biopsy due to elevated PSA or abnormal digital rectal examination, it represents a strategy to refine biopsy decisions after PSA screening rather than as a replacement for it.
Still, they concluded that “these findings suggest that urinary RNA testing can mitigate harms of prostate screening while retaining the benefits of identifying aggressive cancers suitable for treatment.”