Some Low-grade Prostate Cancers Show Molecular Features of Aggressive Disease

Despite having the lowest possible Gleason score, about 20 percent of 3+3=6 prostate cancers harbor genomic alterations that are associated with an increased risk of metastatic disease, according to a study from Cleveland Clinic.

“Our study shows that men with prostate cancer stand to benefit from molecular profiling at the time of diagnosis, in conjunction with Gleason scoring and use of other prognostic tools, because it helps both to improve patient selection for active surveillance and inform treatment decisions for those who require immediate intervention,” says Eric Klein, MD, Chair of Cleveland Clinic Glickman Urological & Kidney Institute.

Dr. Klein and collaborators at some of the nation’s top medical centers evaluated prostatectomy tissue samples from 337 patients with 3+3=6 Gleason prostate tumors using the Decipher® test and blinded pathology assessments to determine the frequency with which disease with metastatic potential may be overlooked.

Results of the study were published in the Journal of Urology.

Specifically, the study shows that one-in-five prostate cancers with the lowest possible Gleason score (3+3=6) harbor molecular alterations consistent with aggressive disease and the potential to metastasize.

Distribution of Decipher® scores by pathological Gleason score category in prospective and retrospective cohorts. Eighty percent of 3+3 Gleason tumors have low risk of metastasis; 13 percent have intermediate risk, and 7 percent have a high risk of metastasis, as measured by Decipher, which assesses tumors for cell-cycle proliferation, adhesion and motility, immune modulation and androgen signaling.

Sample collection and study design

To conduct the study, samples were selected from among two existing cohorts: 2,342 patients who were consented to participate in Decipher testing validation studies from six different institutions, and from 1,507 patients stored in the PCa GRID™, which contains data on men treated at five different institutions. None of the cancers evaluated for the new study have been used previously for Decipher validation.

The Decipher test has emerged as an adjunct prognostic tool that evaluates expression of 22 molecular biomarkers across the genome that are known to predict the likelihood of metastasis, high-grade disease and prostate-cancer specific death for men diagnosed with localized disease.

Samples that had been scored 3+3=6 at the time of prostatectomy were tested with Decipher to determine genomic risk for disease recurrence. Genitourinary pathologists, blinded to genomic scores, subsequently re-reviewed the tumors using 2005 ISUP Gleason grading criteria.

Of men with Gleason 3+3=6 disease, 13 percent had intermediate Decipher scores consistent with questionable outcomes, and 7 percent had cancers with a high likelihood of recurrence and metastasis, according to the study. Only 80 percent had a low Decipher score, the study showed.

Of particular note, Decipher scores were significantly higher among pathological Gleason 3+3=6 specimens from cases with adverse pathological features, such as extraprostatic extension, seminal vesicle involvement or positive margins, according to the study.

Advancing genomics; supporting surveillance

Dr. Klein and collaborators say they plan to continue evaluating the utility and safety of implementing genomics-based testing into clinical care for men with prostate cancer.

As support for active surveillance continues to grow in the United States and abroad, so will the need for tools to select patients appropriately for this conservative approach.

“Study after study has shown that active surveillance represents the best option for many men with low-grade prostate cancer,” says Dr. Klein. “The important thing is to make sure we select the right patients for deferred treatment to improve overall outcomes and reduce the chances that we miss an aggressive cancer.”

Molecular profiling and tumor genomics represent options to achieve this goal.

“Genomics technologies and tumor sequencing techniques have advanced to the point where we are incorporating them into routine care for men with more advanced prostate and other cancers, and low-grade cancers should be no different,” says Dr. Klein.