Negative Bx during AS linked with lower risk of reclassification

“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature.  Dr. Mian is associate professor of surgery in the division of urology at Albany Medical College, Albany, NY.

Repeat prostate biopsy is an essential component of active surveillance protocols for low-risk prostate cancer. Often, multiple repeat biopsies are performed at variable intervals to capture any cancers that may have worsened to higher risk classification while still at a curable stage. However, a recent study by Kearns et al concluded that those men whose surveillance biopsies are free of cancer are at fairly low risk of being reclassified to a worse category (Eur Urol 2018; 73:706-12).

The optimal number, frequency, and candidate for surveillance biopsies have not been well defined. The authors sought to determine the pathologic outcome and the risk of upgrading or reclassification in subsequent repeat biopsies. This report is from a multicenter cohort study (Canary Prostate Active Surveillance Study) that enrolled patients with low-risk prostate cancer who were monitored with PSA test, clinic visits, and surveillance prostate biopsy at 1 year, 2 years, and then every 2 years. The average age of this cohort was 63 years, median PSA was 4.9 ng/mL, and the median prostate volume was 42 cc. The majority (94%) of patients had Gleason 3+3 cancer involving one or two biopsy cores.

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The authors identified 657 men who have undergone at least one surveillance biopsy and 313 men who had undergone a second surveillance biopsy. Reclassification to a higher category was defined as an increase in Gleason score or in the number of cores with cancer.

Of the 657 men undergoing first surveillance repeat prostate biopsy, 214 biopsies (32%) were cancer free, 282 (43%) had cancer but no reclassification, and 161 (25%) were reclassified to worse disease. At the second surveillance biopsy performed in 313 men, 120 (38%) showed no cancer, 139 (44%) had cancer without reclassification, and 54 (17%) were reclassified due to increased volume or grade.

On multivariable analysis, having no cancer in the first surveillance biopsy was protective against higher classification on the second surveillance biopsy. Similarly, if the second surveillance biopsy was free of cancer, it was a strongly predictive of lack of reclassification on subsequent biopsies.

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Other variables predicting persistence of low-risk or no cancer in future biopsies included low PSA level, low PSA density, and low body mass index. Kaplan-Meier estimates demonstrated that time to reclassification to higher risk cancer was significantly longer if either the first or the second surveillance biopsies showed no cancer. Persistence of any cancer in surveillance biopsies was associated with ongoing risk of finding higher risk disease when compared to those who had no cancer (estimated 20%-30% vs. 2%-3%, respectively).

Through a decade-long education effort, active surveillance of low-risk prostate cancer is being adapted with increasing frequency. The frequency and timing of repeat biopsies utilized in clinical practice are quite arbitrary and not based on high-level evidence. The concern of patients and physicians over cancer progression to high grade and/or advanced stage is a major contributor to the frequency of repeat biopsies. However, the requirement of repeat biopsies, with their associated complications (pain, bleeding, infection) may also dissuade some patients or physicians from choosing active surveillance as a safe and effective option.

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All efforts should be made to reduce the complication rates, and one of the best ways to reduce the burden of complications is to reduce the number of biopsies. This study lends further credibility to the idea that frequent repeat biopsies are unnecessary and that clinical variables such as no cancer in the repeat biopsy can be used to inform the decision regarding frequency of biopsies.

This study has a relatively short follow-up and only a few men have had more than three or four biopsies. It will be interesting to learn the outcome of men in their 50s or 60s over the next 10 to 15 years.

Multiparametric magnetic resonance imaging of the prostate and genomic test utilization have increased significantly over the last 5 years. Can imaging and/or genomic tests replace some of the surveillance biopsies? It’s likely that after the initial surveillance biopsy, these modalities will be able to classify some patients into a risk category that is low enough for clinicians to safely omit a number of repeat biopsies.