Genomic tests may offer valuable prognostic insights, but clinical utility remains unclear

A recent systematic review published in Annals of Internal Medicine showed inconsistent findings between observational and randomized studies on the impact of tissue-based genomic classifier tests on risk classification and treatment decisions for patients with localized prostate cancer.^1,2

According to the authors, these findings underscore the need for well-designed trials to evaluate the role of these tests in clinical practice.¹

Amir Alishahi Tabriz, MD, PhD, MPH

“Prostate cancer is the most common cancer among men, with cases ranging from barely noticeable to highly aggressive and requiring serious treatment. Identifying the right treatment for each patient remains a significant challenge. Traditionally, doctors rely on tools like tumor stage, PSA levels, and Gleason grades. While helpful, these tools are not perfect—they can sometimes lead to overtreatment or undertreatment because they don't always accurately predict disease progression,” said lead author Amir Alishahi Tabriz, MD, PhD, MPH, in correspondence with Urology Times®. “This is where genomic classifier tests come into play. Tests like Decipher, Prolaris, and Genomic Prostate Score analyze gene expression to provide more precise insights into tumor behavior and cancer aggressiveness. However, despite their potential, the use of these tests in clinical practice remains inconsistent due to conflicting guidelines.”

For the analysis, the investigators searched for studies published from January 2010 to August 2024 via MEDLINE, EMBASE, and Web of Science. In total, 19 studies were included for analysis. The studies included findings on Decipher, Oncotype DX Genomic Prostate Score, and Prolaris genomic classifiers.

Among the selected studies, 10 reported data on risk reclassification following testing. Findings from observational studies with a low risk of bias showed that patients who were very low or low risk at baseline were not often reclassified to a higher risk group following testing.

However, 1 randomized trial showed an increased level of grade reclassification in these patients. Overall, testing led to a higher risk category among 34.5% of patients with very low risk and 29.4% of patients with low risk at baseline.

“The variation in reclassification rates could stem from differences in initial clinical risk models, patient populations, and test interpretations,” explained Alishahi, who is also an assistant member of the department of health outcomes and behavior at Moffitt Cancer Center in Tampa, Florida. “[Genomic classifier] tests provide a genetic snapshot of tumor aggressiveness, potentially identifying risks that traditional clinical tools might miss.”

The investigators also assessed 12 studies that reported on the impact of testing results on treatment decisions. Results from the observational studies suggested that treatment decisions remained either unchanged or slightly in favor of more conservative management following testing. Conversely, findings from a randomized trial showed a decrease in recommendations for active surveillance following testing with the Oncotype DX Genomic Prostate Score.

Based on the variation in these findings, the authors suggest that better data is needed.

“One area requiring further investigation is the impact of [genomic classifier] tests on racial and ethnic groups, particularly Black men,” said Alishahi. “Some studies suggest traditional classifiers may overlook aggressive tumors in this population, highlighting the need for more inclusive research.”

In addition to evaluating the role of these tests in more diverse populations, the authors also suggest a need for clarity on which clinical situations would derive the most benefit from genomic classifiers, as well as the financial impact of testing.

“In conclusion, genomic classifier tests offer valuable prognostic information and could help reduce overtreatment in localized prostate cancer,” said Alishahi. “However, their full integration into clinical practice requires additional research to better understand their cost-effectiveness, clinical utility, and impact on diverse populations.”

References

1. Tabriz AA, Boyer MJ, Gordon AM, et al. Impact of genomic classifiers on risk stratification and treatment intensity in patients with localized prostate cancer : A systematic review. Ann Intern Med. 2025. doi:10.7326/ANNALS-24-00700

2. Gene classifier tests for prostate cancer may influence treatment decisions despite lack of evidence for long-term outcomes. News release. American College of Physicians (ACP). January 14, 2025. Accessed January 22, 2025. https://www.eurekalert.org/news-releases/1070333