Study finds 1 in 12 patients labeled as having ‘benign’ results actually had high-risk prostate cancer

New research highlights the challenge of balancing the risks of overdiagnosing and underdiagnosing prostate cancer early enough to intervene and minimize risk of death. Recently, some experts have called for the lowest grade of prostate cancer—biopsy Gleason Grade Group (GGG) 1—to be reclassified as ‘benign.’ But a new study led by a researcher from Mass General Brigham has found that many patients with a biopsy GGG1 may have a more aggressive cancer than their biopsy alone suggests.

By looking at data from more than 10,000 patients at a university in Germany, researchers found that at least 8 percent of patients with this classification had a more aggressive form of prostate cancer. They also found that many of the patients with GGG1 who are at highest risk can be identified based on high PSA levels or 50 percent or more of their biopsy samples coming back positive. Maintaining a “cancer” classification for these higher risk patients could improve their treatment plan and minimize risk of death. Results are published in European Urology Oncology.

“Our study identifies two risk factors that help determine which patients with GGG1 are at heightened risk of aggressive disease and death,” said senior author Anthony D’Amico, MD, PhD, of the Department of Radiation Oncology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “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.”

D’Amico collaborated with colleagues from 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. The study began enrolling patients in February 1992 and continued following them through November 2023.

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.

The authors note potential limitations to their study, including that the study population is from a single institution, PSA levels prior to diagnosis were not available, and most patients had samples collected and diagnosed before combined biopsy became widely adopted and diagnostic guidelines were updated in 2014. However, researchers found the same result for what predicts increased risk of adverse pathology and early recurrence (within 18 months) despite taking the prostate out in patients diagnosed with both approaches.

D’Amico notes that for patients with GGG1 who have one or both indicators of heightened risk, there are steps that clinicians can take, such as doing a follow-up biopsy sooner or recommending genomic testing, to assess if aggressive prostate cancer is present but missed on initial biopsy so as to intervene earlier to minimize risk of aggressive disease and death/

“Physicians and patients can have an informed discussion about whether observation, active surveillance or treatment is the right approach,” he said. “But if all patients with GGG1 are labeled ‘benign,’ it may preclude those conversations from happening.”

Authorship: D’Amico’s co-authors on the paper include Derya Tilki, Ming-Hui Chen, Hartwig Huland, and Markus Graefen.

Paper cited: Tilki D et al. “Mortality Risk in patients with Biopsy Gleason Grade Group 1 Prostate Cancer” European Urology Oncology DOI: 10.1016/j.euo.2024.06.009

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