Rethinking prostate cancer risk in GG1 diagnoses

A new study reveals that some men who are diagnosed with “Grade Group one” (GG1) prostate cancer may actually be at higher risk than biopsy results suggest, according to research led by Weill Cornell Medicine, University Hospitals Cleveland and Case Western University. The researchers conclude 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.

The study, published July 31 in the journal JAMA Oncology, found that one in six men with GG1 category cancer turns out to have intermediate- or high-risk cancer when other clinical features are considered in addition to biopsy results. “We don’t want to miss aggressive cancers that initially present as Grade Group one on biopsy,” said co-senior author Dr. Bashir Al Hussein, an assistant professor of urology and population health sciences at Weill Cornell Medicine. “Such underestimation of risk could lead to undertreatment and poor outcomes.”

The study results could also inform recent discussions on whether to drop the cancer label completely for GG1 tumors.

There is a misunderstanding that ‘low grade’ and ‘low risk’ are the same. Here, we show clearly that they are not. Attempts to rename GG1 are misguided as many patients with GG1 cancers on biopsy have substantial risks of their cancers causing pain and suffering over their lifetime if untreated.”

Dr. Jonathan Shoag, co-senior author, associate professor of urology at Case Western Reserve University and an urologist at University Hospitals Cleveland

Accurately categorizing tumors guides treatment

The team drew on data collected between 2010 and 2020 by the National Cancer Institute’s Surveillance, Epidemiology and End Results Program. “This is real-world, contemporary data representing all men diagnosed with prostate cancer across the United States,” said Dr. Al Hussein, who is also a urologist at NewYork-Presbyterian/Weill Cornell Medical Center and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. The data included about 300,000 men who were diagnosed with cancer that was localized to the prostate.

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. 

But what if some of these men harbored more aggressive prostate cancers than suggested by their biopsy grade alone? Dr. Al Hussein and his colleagues 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 discovered that more than 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 percent of patients who were diagnosed with GG1 but were in the higher risk category underwent active surveillance, which means they were potentially undertreated,” Dr. Al Hussein said.

What’s in a name

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. They argue that most tumors categorized as GG1 grow slowly and rarely spread or cause harm. 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,” explained Dr. Shoag. “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 is based largely on previous studies of prostatectomy specimens, which examined the whole prostate once it was removed.

“A subset of men with low-grade tumors has adverse clinical features that are associated with worse cancer outcomes. We need to better understand this biology, which could help clinicians improve prognosis,” said first author Dr. Neal Arvind Patel, assistant professor of clinical urology, an urologist at NewYork-Presbyterian/Weill Cornell Medical Center and a member of the Meyer Cancer Center.

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.”

This research is supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust.