Patients classified with "grade group 1" prostate cancer face a wide range of long-term outcomes, according to findings from a study published in JAMA Oncology. Investigators revealed that as many as one in six men with grade group 1 prostate cancers have intermediate- or high-risk disease when factoring in other clinical features beyond just biopsies.
As such, the study authors believe that classifying tumors by grade group alone based on biopsies may lead to potential underestimation of disease risk and undertreatment.
“There is a misunderstanding that ‘low grade’ and ‘low risk’ are the same. Here, we show clearly that they are not,” said co-senior study author Jonathan Shoag, MD, Associate Professor of Urology at Case Western Reserve University and Urologist at University Hospitals Cleveland. “Attempts to rename grade group 1 are misguided, as many patients with grade group 1 cancers on biopsy have substantial risks of their cancers causing pain and suffering over their lifetime if untreated.”
Background and Study Methods
Researchers have recently been discussing dropping the cancer label completely for grade group 1 tumors, as rates of metastasis are low when based on biopsy alone. But this research could provide helpful findings to inform the discussion.
The study authors conducted a contemporary population-based cohort study using the National Cancer Institute's Surveillance, Epidemiology, and End Results data to assess cancer-specific outcomes for men with grade group 1 prostate cancers. Among 300,000 men with prostate cancer diagnosed between 2010 and 2020, the researchers looked at 117,162 with localized grade group 1 prostate cancer cancers, according to National Comprehensive Cancer Network risk groups.
“We don’t want to miss aggressive cancers that initially present as grade group 1 on biopsy,” said co-senior author Bashir Al Hussein, MPH, MD, Assistant Professor of Urology and Population Health Sciences at Weill Cornell Medicine; Urologist at NewYork-Presbyterian/Weill Cornell Medical Center; and Member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. “Such underestimation of risk could lead to undertreatment and poor outcomes.”
The team assessed rates of prostate cancer–specific mortality and associations with adverse pathology at the time of prostatectomy based on grade.
Key Study Findings
Of the patients analyzed with grade group 1 prostate cancer, the majority (85%) had low-risk disease. However, 9% of the cohort had favorable intermediate-risk disease, 3% had unfavorable intermediate-risk disease, and 4% had high-risk disease. Of the patients with high-risk disease, 60% had adverse pathology at the time of prostatectomy.
Up to 30% of patients with higher-risk grade group 1 tumors underwent active surveillance, "which means they were potentially undertreated," said Dr. Al Hussein.
Prostate cancer–specific mortality rates were 2.4% for unfavorable intermediate-risk grade group 1 disease and 4.7% for high-risk grade group 1 disease. These rates were considered comparable to the prostate cancer–specific mortality rates for favorable intermediate-risk grade group 2 disease and unfavorable intermediate-risk group group 2 disease rates of 2.1% and 4.0%, respectively.
Adjusted analyses showed associations between an increased risk of prostate cancer–specific mortality and favorable intermediate-risk grade group 1 disease (adjusted hazard ratio [aHR] = 1.60; 95% confidence interval [CI] = 1.30–1.96), unfavorable intermediate-risk grade group 1 disease (aHR = 2.10; 95% CI = 1.53–2.89), and high-risk grade group 1 disease (aHR = 3.58; 95% CI = 2.93–4.38), all compared with low-risk grade group 1 disease.
“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 study author Neal Arvind Patel, MD, Assistant Professor of Clinical Urology at Weill Cornell Medical College; Urologist at NewYork-Presbyterian/Weill Cornell Medical Center; and Member of the Meyer Cancer Center.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
