Biopsy grade alone may underestimate risk in GG1 prostate cancer

Recent data published in JAMA Oncology show that 1 in 6 men with grade group 1 (GG1) prostate cancer ultimately had intermediate- to high-risk disease when other clinical features were taken into account.¹

According to the authors, these data suggest that relying on biopsy grade alone can lead to an underestimation of disease risk.

“We don’t want to miss aggressive cancers that initially present as grade group 1 on biopsy,” explained co-senior author Bashir Al Hussein Al Awamlh, MD, MPH, an assistant professor of urology and population health sciences at Weill Cornell Medicine in New York, New York, in a news release on the findings.² “Such underestimation of risk could lead to undertreatment and poor outcomes.”

In total, the cohort study included data from 117,162 patients with localized GG1 prostate cancer. Data were obtained from the Surveillance, Epidemiology, and End Results database. The median age of patients was 64 years (IQR, 58 to 69). 

Among these patients with GG1 prostate cancer, 10,440 (9%) had favorable intermediate-risk disease, 3145 (3%) had unfavorable intermediate-risk disease, and 4539 (4%) had high-risk disease when clinical data such as prostate-specific antigen levels and tumor sizes were considered. Of the patients with high-risk GG1 prostate cancer, 867 (60%) were found to have adverse pathology at prostatectomy.

Al Hussein added, “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.”

The prostate cancer-specific mortality (PCSM) rate was 2.4% for patients with unfavorable intermediate-risk GG1 disease and 4.7% for patients with high-risk GG1 disease. Further, the PCSM rates for patients with favorable intermediate-risk GG2 disease and unfavorable intermediate risk GG2 or higher disease were 2.1% and 4.0%, respectively.

Compared with patients with low-risk GG1 disease, the risk of PCSM was higher for patients with favorable intermediate-risk GG1 disease (aHR, 1.60; 95% CI, 1.30 to 1.96), unfavorable intermediate-risk GG1 disease (aHR, 2.10; 95% CI, 1.53 to 2.89), and high-risk GG1 disease (aHR, 3.58; 95% CI, 2.93 to 4.38).

“These data indicate that not all GG1 prostate cancer follows an indolent course,” the authors wrote. “A subset of men with biopsy GG1 prostate cancer have outcomes comparable to those of men with higher-grade intermediate-risk prostate cancer, a group that often undergoes treatment.”

The authors also suggested that these findings may inform ongoing discussions surrounding whether to drop the ‘cancer’ label for GG1 tumors.

“There is a misunderstanding that ‘low grade’ and ‘low risk’ are the same. Here, we show clearly that they are not,” said co-senior author Jonathan Shoag, MD, associate professor of urology at Case Western Reserve University and an urologist at University Hospitals Cleveland, in the news release.² “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.”

Ultimately, these findings can be used to improve patient counseling for those who are determined to have GG1 disease.

“We need to find a better way to inform patients about their prognosis when they have GG1 prostate cancer with adverse clinical features,” Al Hussein concluded in the news release.² “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.”

REFERENCES:

1. Patel NA, Barocas DA, Lin DW, et al. Grade group 1 prostate cancer outcome by biopsy grade and risk group. JAMA Oncol. 2025. doi:10.1001/jamaoncol.2025.2304

2. Not all low-grade prostate cancers are low risk. News release. Weill Cornell Medicine. July 31, 2025. Accessed August 1, 2025. https://news.weill.cornell.edu/news/2025/07/not-all-low-grade-prostate-cancers-are-low-risk