Some men who are diagnosed with “Grade Group one” (GG1) prostate cancer may actually be at higher risk than biopsy results suggest, according to recently published research led by Weill Cornell Medicine, University Hospitals Cleveland, and Case Western Reserve University.1
The team drew on data collected from approximately 300,000 men between 2010 and 2020 by the National Cancer Institute’s SEER Program, a real-world, contemporary data program, which represents all men diagnosed with prostate cancer across the United States.
Approximately 117,000 of those men had a biopsy that was categorized as GG1. This grade is often used synonymously with a low risk for progression to metastasis, or cancer spreading to other parts of the body. They are usually followed through active surveillance—blood tests to monitor a protein produced by the prostate, additional biopsies, and MRI scans. Increasing prostate-specific antigen (PSA) levels in the blood can indicate cancer progression.
However, what if some of these men harbored more aggressive prostate cancers than suggested by their biopsy grade alone? The researchers further analyzed the individuals in the GG1 group with their clinical data, such as PSA levels and tumor sizes. When all the data were factored in, the researchers noted that >18,000 of these men had higher-risk cancers that are often treated with radiation therapy or removal of the prostate (radical prostatectomy).
“Our data show that up to 30% of patients who were diagnosed with GG1 but were in the higher risk category underwent active surveillance, which means they were potentially undertreated,” Bashir Al Hussein, MD, MPH, assistant professor of Urology and Population Health Sciences at Weill Cornell Medicine, a urologist at New York-Presbyterian/Weill Cornell Medical Center, and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, explained in a statement about the findings.
Understanding how cancer classification correlates with clinical outcomes is particularly critical, as some physicians advocate removing the cancer label from GG1 prostate cancer, which could reduce anxiety and unnecessary treatment. However, the paper advises that a one-size-fits-all approach is risky.
“There has been an unfortunate conflation of several different terms by some of my colleagues who are trying to rename GG1 cancer,” Jonathan Shoag, MD, associate professor of urology at Case Western Reserve University and a urologist at University Hospitals Cleveland, noted in the statement. “One is that biopsy GG1 and prostatectomy GG1 are similar, but they are not. As clinicians, we must make decisions based on each patient and his biopsy results in that context.” The data suggesting that GG1 cancers do not spread are based largely on previous studies of prostatectomy specimens, which examined the whole prostate once it was removed.
Dr Al Hussein also sees room for improving how patients are counseled. “We need to find a better way to inform patients about their prognosis when they have GG1 prostate cancer with adverse clinical features,” he said. “As physicians, the responsibility falls on us to educate patients and provide them with the information they need to understand their diagnosis and decide on the best approach for treatment, while continuing to advocate for active surveillance for those who are indeed low risk.”
The researchers concluded that relying on biopsy grade alone can lead to underestimating disease risk and misclassifying individuals who may benefit from definitive treatment with either surgery or radiation. Biopsies test only small areas of the prostate, so they can miss more advanced or aggressive cancer cells, providing an incomplete picture.
This research was supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.
Reference
- Weill Cornell Medicine. Not all low-grade prostate cancers are low risk [news release]. July 31, 2025. Accessed August 15, 2025. https://news.weill.cornell.edu/news/2025/07/not-all-low-grade-prostate-cancers-are-low-risk