Biomarker assay/mpMRI predict grade reclassification

While both the Prostate Health Index (phi) and multiparametric magnetic resonance imaging (mpMRI) have demonstrated value for predicting grade reclassification among patients enrolled in active surveillance for prostate cancer, combining the two tools provides greater accuracy than either modality alone, according to research presented at the AUA annual meeting in San Francisco.

Furthermore, the combination appears to be a more powerful predictor of grade reclassification than the combination of mpMRI and PSA density (PSAD), which has been previously shown to be useful in the active surveillance population, Johns Hopkins researchers reported.

The improved predictive performance of combining information from the serum biomarker assay and mpMRI was identified in a retrospective study that included data from 253 men enrolled in the Johns Hopkins Active Surveillance program. The results showed that a cutoff of <25.6 for phi, which encompasses the lowest quartile of scores in the study population, combined with a PI-RADS v2 score ≤3, had a 98% negative predictive value (NPV) for grade reclassification to Gleason score >6 and an area under the curve (AUC) of 0.70.

Also see: How is surveillance used in younger men?

Additional calculations determined that the use of both parameters to guide biopsy decisions for men enrolled in active surveillance would avoid nearly 20% of surveillance biopsies at the cost of missing only 2.6% of cases of clinically significant disease, said first author Zeyad Schwen, MD, resident at James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore.

“We have been using phi and mpMRI in the follow-up of men in our active surveillance program. According to our new analysis, the combination of these tools might provide greater accuracy for reducing the number of unnecessary surveillance biopsies while minimizing the risk of missing men who may require active treatment,” said Dr. Schwen, who worked on the study with H. Ballentine Carter, MD, and colleagues.

Men were selected for inclusion in the study if they underwent mpMRI and had a phi test within 6 months of each other and subsequently had systematic biopsy with or without targeted biopsy. All men were categorized as either very-low risk or low-risk according to National Comprehensive Cancer Network Guidelines (NCCN) criteria.

The 253 men had been in active surveillance for a median of 24 months (range, 8 to 52 months). Median PSA, PSA density (PSAD), phi, and phi density (PHID) values for the cohort were 6.2 ng/mL, 0.10 ng/mL², 32.9, and 0.59, respectively. Of the 253 men, 179 (71%) had a PI-RADs v2 score ≤3.

Thirty-eight men (15%) had grade reclassification on surveillance biopsy. Compared to the group of men without grade reclassification, the men with reclassification had significantly higher median phi, PHID, and PSA density (PSAD) values. The percentages of men with PI-RADS v2 4-5 and who were NCCN low-risk were also significantly greater in the group with grade reclassification.

“Not surprisingly, median PSA did not differ significantly between men who did and did not have grade reclassification, showing the limitations of PSA use in the active surveillance population,” Dr. Schwen told Urology Times.

Next: PSAD, PHID, phi all predict reclassification

In univariate analysis, PSAD, PHID, and phi were all found to be significant predictors of grade reclassification, whether the analysis was based on a per unit increase or considered the upper limit of the 25^thpercentile as a cutoff.

The 25^thpercentile cutoff value for each of the biomarkers was then used to evaluate the performance of the biomarker alone and combined with a PI-RADS v2 score ≤3 for predicting grade reclassification. phi<25.6 had the highest NPV and AUC values of the three biomarkers, and it also had a higher NPV than PI-RADS v2 ≤3 used alone.

“phi appears to outperform PSAD in the active surveillance population both when used alone as well as when combined with mpMRI, which advocates for a more widespread adoption of phi in active surveillance programs,” Dr. Schwen said.

Read: mpMRI Bx protocol may reduce repeat biopsies, but at what cost?

Dr. Schwen noted that annual biopsies were performed routinely when the Johns Hopkins Active Surveillance program was launched.

“We have learned a lot since then and the protocol has been modified over time. Currently, we are using the findings from mpMRI, serum biomarkers, and other patient characteristics in decisions about extending the interval and minimizing the morbidities associated with surveillance biopsies,” he said.

“We also believe reducing the number of biopsies will improve active surveillance compliance.”

One of Dr. Schwen’s co-authors is a consultant/adviser for GenomeDx Biosciences and HealthTronics and conducts scientific studies/trials for Novartis.