A recent study involving over 10,000 patients diagnosed with the lowest grade of prostate cancer, known as Biopsy Gleason Grade Group (GGG) 1, revealed that 8 percent of these patients had high-risk prostate cancer despite their initial diagnosis. Identifying two key risk factors, elevated PSA levels and having over 50 percent positive biopsies, can help pinpoint patients with GGG1 who are at a greater risk of aggressive prostate cancer and higher mortality rates.
Recent research underscores the complexity of accurately diagnosing prostate cancer to strike a balance between overdiagnosis and underdiagnosis. While there have been calls to reclassify the lowest grade of prostate cancer as ‘benign,’ a new study led by a researcher from Mass General Brigham challenges this notion by revealing that many patients initially labeled with GGG1 may have a more aggressive form of the disease.
Examining data from a university in Germany involving more than 10,000 patients, researchers found that at least 8 percent of those diagnosed with GGG1 actually had a more aggressive type of prostate cancer. The study also identified that markers such as elevated PSA levels or a high percentage of positive biopsy samples can help identify patients at higher risk. Maintaining the cancer classification for these high-risk patients could lead to better treatment strategies and reduce mortality rates. The findings have been published in European Urology Oncology.
“Our study pinpoints two crucial risk factors for identifying patients with GGG1 who are at a higher risk of aggressive disease and mortality,” stated senior author Anthony D’Amico, MD, PhD, from the Department of Radiation Oncology at Brigham and Women’s Hospital within Mass General Brigham. “For patients with GGG1 at elevated risk, it is vital to retain the cancer diagnosis and inform their physicians for appropriate action. For patients without these risk factors, the risk of mortality is significantly lower. However, for those at higher risk, the message is clear: acknowledge the cancer diagnosis and delve deeper.”
D’Amico collaborated with counterparts from University Hospital Hamburg Eppendorf to analyze data from 10,228 patients with GGG1 prostate cancer who underwent radical prostatectomy at the German university hospital. Out of these patients, 9,249 were diagnosed via transrectal ultrasound (TRUS)-guided biopsies, while 980 were diagnosed using a combination of TRUS and MRI for more precise cancer detection. The study spanned from February 1992 to November 2023.
Within the study group, 10.33 percent of patients diagnosed via TRUS and 7.86 percent of those diagnosed using the combined approach exhibited adverse pathology during radical prostatectomy, indicating higher-risk disease. Approximately 6 percent of GGG1 patients had PSA levels exceeding 20 ng/ml, and 12-14 percent had over half of their biopsies return positive results. Patients with these indicators faced markedly elevated risks of adverse pathology, early PSA failure, and mortality.
The researchers acknowledge some study limitations, such as the single-institution study population, unavailability of pre-diagnosis PSA levels, and the majority of patients being diagnosed before the widespread adoption of combined biopsy and updated diagnostic guidelines in 2014. Nevertheless, the study consistently identified factors predicting higher risks of adverse pathology and early recurrence post-surgery, irrespective of the diagnostic approach.
D’Amico recommends specific actions for GGG1 patients with heightened risk indicators, including early follow-up biopsies or genomic testing to detect potentially missed aggressive cancer, thereby enabling early interventions to mitigate severe disease and mortality risks.
“Physicians and patients should engage in informed discussions regarding observation, active surveillance, or treatment based on individual cases,” he advocated. “Designating all GGG1 cases as ‘benign’ could hinder these critical conversations.”
The co-authors of the study along with D’Amico include Derya Tilki, Ming-Hui Chen, Hartwig Huland, and Markus Graefen.
