Recently, some experts have called for Gleason Grade Group 1 prostate cancer to be reclassified as benign. However, many patients diagnosed with this lowest grade of prostate cancer may have more aggressive disease than their biopsy alone suggests, according to a recent study published by Tilki et al in European Urology Oncology. The findings highlighted the challenges of balancing the risks of overdiagnosing and underdiagnosing prostate cancer early enough to intervene and minimize the risk of mortality.
Study Methods and Results
In the recent study, the investigators analyzed the data of 10,228 patients with Gleason Grade Group 1 prostate cancer who underwent radical prostatectomy at University Hospital Hamburg Eppendorf in Germany. Among these patients, 9,249 of them were diagnosed based on transrectal ultrasound (TRUS)-guided biopsies, and 980 of them were diagnosed using a more modern approach combining TRUS with magnetic resonance imaging to detect prostate cancer more accurately. The investigators began enrolling patients in February 1992 and continued following them through November 2023.
Adverse pathology—a higher-grade Gleason Group Score or positive pelvic lymph nodes—at the time of radical prostatectomy was found in 10.3% (n = 955) of the patients diagnosed using TRUS and 7.9% (n = 77) of those diagnosed using the combined biopsy approach.
The investigators found that at least 8% of the patients with a classification of Gleason Grade Group 1 had a more aggressive type of prostate cancer. However, about 6% of the patients with Gleason Grade Group 1 classification who were at highest risk for aggressive prostate cancer had a prostate-specific antigen (PSA) level of 20 ng/mL or higher, and about 12% to 14% of them had more than 50% of their systematic biopsies return a positive result. The patients who had either of these indicators had a significantly elevated risk of adverse pathology, early PSA failure, and mortality.
Conclusions
The investigators proposed that maintaining a cancer classification for these higher-risk patients could improve their treatment plan and reduce their risk of mortality.
“Our study identifies two risk factors that help determine which patients with [Gleason Grade Group 1] are at heightened risk of aggressive disease and death,” explained senior study author Anthony D’Amico, MD, PhD, of the Department of Radiation Oncology at Brigham and Women’s Hospital and a founding member of the Mass General Brigham health-care system. “For patients with [Gleason Grade Group 1 classification] 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 [this classification] who do not have either of these risk factors, the chance of dying is much lower. [F]or [physicians] caring for patients at greatest risk, our message is clear: call it cancer, and look harder,” he emphasized.
The investigators reported potential limitations to their study, including that the participants were from a single institution, PSA levels prior to diagnosis were not available, and most of the patients had samples collected and diagnosed prior to the widespread adoption of combined biopsy and updated diagnostic guidelines in 2014. Nonetheless, they demonstrated the same results for predictors of an increased risk of adverse pathology and early recurrence—despite patients diagnosed with both approaches having undergone radical prostatectomy.
The investigators advised physicians to perform follow-up biopsies sooner or recommend genomic testing to assess if aggressive prostate cancer is present but missed on initial biopsy in patients with Gleason grade Group 1 prostate cancer who have one or both indicators of heightened risk. This may allow them to intervene earlier and increase the likelihood of survival.
“Physicians and patients can have an informed discussion about whether observation, active surveillance, or treatment is the right approach, but if all patients with [Gleason Grade Group 1 classification] are labeled ‘benign,’ it may preclude those conversations from happening,” concluded Dr. D’Amico.
Disclosure: For full disclosures of the study authors, visit euoncology.europeanurology.com.