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Urine biomarkers may reduce repeat biopsies for prostate cancer
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Incorporating scores from two urine-based biomarker assays may reduce the number of biopsies men with clinically localized prostate cancer need to undergo without greatly affecting 10-year survival rates, according to the results of a decision analysis.
“Results from recent studies have demonstrated the potential clinical utility of the urine-based PROGENSA prostate cancer antigen 3 (PCA3) assay (Gen-Probe, Inc.) to predict repeat biopsy outcomes in men with elevated serum PSA levels and previous negative biopsy findings,” Brian T. Denton, PhD, associate professor of industrial and operations engineering at University of Michigan, and colleagues wrote. “A recent literature review reported current evidence suggesting that the PCA3 test is clinically useful for selecting which patients should undergo repeat biopsy. Several studies have determined that urine assessment of [T2:ERG] is also associated with biopsy outcome and may be better at discriminating between low-grade and high-grade cancers."
Denton and colleagues performed a decision analysis using a decision tree to evaluate the clinical value of using PCA3 and T2:ERG scores to determine the need for repeat biopsy in men with clinically localized prostate cancer who had at least one prior negative biopsy. Researchers estimated the probability for cancer by using the Prostate Cancer Prevention Trial Risk Calculator.
The analysis compared the use of PSA alone with the use of PCA3 or T2:ERG scores — with each score evaluated independently — in combination with PSA to trigger a repeat biopsy.
The researchers defined biopsy outcomes as positive (with a Gleason score of < 7, 7 or > 7) or negative. They derived probabilities and estimates of 10-year OS and 15-year disease-specific survival from previous studies and a literature review.
The study included data from 420 men (mean age, 66.3 ± 8.5 years) with previous negative biopsies. Two-hundred eighty of the men continued to have a negative biopsy, but 140 men had a positive biopsy.
The results of the decision analysis showed that incorporating the PCA3 score at a biopsy threshold of 25 — generated based on the urine PCA3 level normalized to the amount of PSA messenger RNA — would detect 72.4% of Gleason score 7 or higher cancers and would have avoided 52.4% of recommended repeat biopsies. The incorporation of a T2:ERG score at a biopsy threshold of 10 — generated based on the urine T2:ERG level normalized to the amount of PSA messenger RNA — would identify 56.9% of Gleason score 7 or higher cancers and would have avoided 62.1% of biopsies.
Researchers considered a base-case patient who was white, aged 65 years, had a serum PSA of 6.3 ng/mL, a Charlson Comorbidity Index of 1, no family history of prostate cancer, normal digital rectal exam and a previous negative biopsy. Results showed a PCA3 score (biopsy threshold, 25) would have avoid 55.4% of repeat biopsies, whereas the T2:ERG score (biopsy threshold, 10) would avoid 64.7% of repeat biopsies for the base-case patient.
Further, the researchers noted that only small changes to 10-year OS (PCA3, 0.93%; T2:ERG, 1.41%) would have resulted from the addition of PCA3 or T2:ERG scores into the decision to undergo biopsy.
However, multi-way sensitivity analyses demonstrated that repeat biopsy yielded better 10-year OS than biomarkers at repeat biopsy under every protocol with various PCA3 and T2:ERG thresholds, with similar results for 15-year disease-specific survival.
The researchers acknowledged several study limitations, including the small number of study patients with clinically insignificant prostate cancer and the use of survival estimates and biopsy sensitivity.
“The addition of PCA3 or T2:ERG tests to the decision-making process for recommending a repeat biopsy can reduce the number of biopsies substantially; however, this is associated with some reduction in 10-year OS and 15-years disease-specific survival,” Denton and colleagues wrote. “Decisions about whether to use PCA3 or T2:ERG at repeat biopsy should weigh these competing considerations.” – by Cameron Kelsall
Disclosure: Denton reports no relevant financial disclosures. One study researcher reports personal fees from Roche/Ventana Medical Systems outside of the submitted work, as well as co-inventing a patent for ETS gene fusions in prostate cancer held by University of Michigan.
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