Cell-cycle risk score is predictive of ADT benefit in prostate cancer

Data from a recently published study showed that the Prolaris Test, a personalized clinical cell-cycle risk (CCR) score to inform 10-year metastasis risk, can accurately predict which patients may benefit from adding androgen deprivation therapy (ADT) to radiation therapy for the treatment of prostate cancer.¹

The investigators assumed a relative benefit from ADT of 41% based on a meta-analysis of randomized trials.

The findings were first presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Conference and were also recently published in JCO Precision Oncology.

“This study was a robust analysis that used level 1 evidence from many prospective randomized studies to determine the risk reduction. Prolaris precisely describes the difference in metastasis outcomes for men receiving monotherapy (RT) vs multimodal therapy (RT+ADT), and further tells me precisely what the risk of death is for a man on surveillance. This is something that none of the other classifiers can currently perform,” said lead author Jonathan D. Tward, MD, PhD, in a news release on the findings.² Tward is a professor in the department of radiation oncologyat the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

Data from the study showed that the absolute risk reduction from ADT increased from nearly 0 with low CCR scores to 17.1% when the CCR score was 3.690. This corresponded with a number needed to treat (NNT) of 6, indicating that metastasis within 10 years would be prevented in 1 in 6 patients who received ADT in addition to radiation therapy.

Further, patients who had a CCR score below the validated multimodal treatment threshold of 2.112 had an average absolute risk reduction of 0.86%, corresponding to an NNT of 116. However, patients who had a CCR score above the multimodal treatment threshold demonstrated an average absolute risk reduction of 8.19%, corresponding to an NNT of 12.

The authors added,¹ “The average [absolute risk reduction] observed in those above the [multimodal treatment] threshold was even higher than the 7.06% average [absolute risk reduction] observed in the NCCN high-risk subset of the cohort, demonstrating the utility of the CCR score in predicting the benefit of adding ADT to RT.”

Additional data from the study showed broad ranges of ADT benefit across National Comprehensive Cancer Network risk groups.

“In light of the appreciable side effects of ADT, it is enormously valuable for patients with prostate cancer to have a test that can quantify the extent to which they may benefit from ADT,” said Dale Muzzey, chief scientific officer of Myriad Genetics, in the news release.¹ “Notably, more than 85% of patients we have tested with Prolaris have a CCR score below the multimodal threshold and accordingly have an average of <1% risk reduction by adding ADT to RT. In consultation with their providers, many of these men may elect to forgo ADT based on the information in their Prolaris reports.”

For the study, the model of absolute risk reduction was developed using a retrospective cohort of 467 men who were tested with Prolaris and received radiation therapy alone. The absolute risk reduction and the number needed to treat were derived from a cohort of 56,485 patients who were clinically tested with Prolaris between January 2020 and October 2022. The investigators assumed a relative benefit from ADT of 41% based on a meta-analysis of randomized trials.

References

1. Tward JD, Lenz L, Gutin A, et al. Using the cell-cycle risk score to predict the benefit of androgen-deprivation therapy added to radiation therapy in patients with newly diagnosed prostate cancer. JCO Precis Oncol. 2024 May:8:e2300722. doi:10.1200/PO.23.00722

2. New study published in JCO Precision Oncology shows Myriad Genetics' Prolaris Test can predict benefit of hormone therapy treatment in men with localized prostate cancer. News release. Myriad Genetics, Inc. May 16, 2024. Accessed May 17, 2024. https://www.biospace.com/article/releases/new-study-published-in-jco-precision-oncology-shows-myriad-genetics-prolaris-test-can-predict-benefit-of-hormone-therapy-treatment-in-men-with-localized-prostate-cancer/?s=86