Researchers have known for some time that about seven percent of people diagnosed with low-risk prostate cancer following a biopsy actually have the deadly form of the disease. Recently, some experts have called for the lowest grade of prostate cancer—biopsy Gleason Grade Group (GGG) 1—to be reclassified as “benign.” A new study has not only confirmed previous research regarding the rate of misdiagnosis among patients with a biopsy GGG1, but identifies which patients should receive genomic and follow-up PSA testing to confirm their “benign” diagnosis.
“The purpose of the study was to see if we could identify who with this particular biopsy finding has a cancer that in fact is much more aggressive than the biopsy finding suggests,” said Anthony D’Amico, MD, PhD, senior author of the study published in European Urology Oncology. D’amico is professor of Radiation Oncology at Harvard Medical School and is the chief of Genitourinary Radiation Oncology at the Brigham and Women’s Hospital and Dana-Farber Cancer Institute.
“Our study identifies two risk factors that help determine which patients with GGG 1 are at heightened risk of aggressive disease and death,” D’Amico said. The first risk factor in this group of patients is a PSA over 20. The second is more than half of their biopsies showing a Gleason score of 6.
The Prostate-Specific Antigen, or PSA, test is used to monitor prostate health and the progression of prostate cancer by measuring the amount of PSA protein in the blood. The antigen is produced by both healthy and malignant cells, but the levels of the protein are higher in those with cancer. The Gleason score is derived from the biopsy of the prostate, which involves taking 12 microscopic core samples from the tumor with a hollow needle. The pathologist assigning the score will assign one Gleason grade to the most predominant pattern in the biopsy and a second Gleason grade to the second most predominant pattern. The two are added together to get the Gleason score, which normally ranges from 6 to 10.
“For patients with GGG1 who are at heightened risk, we should continue to call their diagnosis cancer and we should report it back to their physician so that they can act on this information. For patients with GGG1 who do not have either of these risk factors, the chance of dying is much lower. But for clinicians caring for patients at greatest risk, our message is clear: Call it cancer, and look harder.”
In the current study, D’Amico collaborated with colleagues from the University Hospital Hamburg Eppendorf to analyze data from 10,228 patients with GGG1 prostate cancer who underwent radical prostatectomy (surgical removal of the prostate) at the university hospital in Germany. Of these patients, 9,249 were diagnosed based on transrectal ultrasound (TRUS)-guided biopsies, and 980 were diagnosed using a more modern approach that combines TRUS with MRI to detect prostate cancer more accurately.
Of the 10,228 patients in the study cohort, adverse pathology—that is, a higher-grade Gleason Group Score or positive pelvic lymph nodes—at the time of radical prostatectomy was found in 955 of 9,248 patients diagnosed using TRUS (10.33 percent) and 77 of 980 patients diagnosed using the combined biopsy approach (7.86 percent). About 6 percent of patients with GGG1 had a PSA level of 20 ng/ml or more and about 12–14 percent of patients with GGG1 had more than half of their systematic biopsies return a positive result. Patients with either of these indicators had a significantly elevated risk of adverse pathology, increased risk for early PSA failure, and risk of death.
D’Amico and his colleagues are now set on further characterizing the subgroup of GGG1 patients with PSA’s over 20 and more than half of their biopsies showing Gleason scores of 6 and applying artificial intelligence to combined data, such as radiographs and PSA, and genomic tests. “I think that for today, there’s enough information already to say more needs to be done. You don’t just call these [tumors] benign and you don’t just say, ‘I’ll see you next year.’ You act; go forward with getting more information on them.”
