According to a retrospective study, the combined clinical and cell-cycle risk (CCR) score may be able to accurately predict which patients with intermediate- and high-risk prostate cancer will have little additional benefit from androgen-deprivation therapy added to dose-escalated radiotherapy and which patients should be treated with both therapeutic modalities.1 The ability to decide which patients need intensified therapy based on a validated tool such as CCR may optimize therapeutic decision-making, spare some patients from the side effects of androgen-deprivation therapy, and reduce the costs of therapy.
“Patients with scores below a certain threshold may see very little additional benefit from adding androgen-deprivation therapy to dose-escalated radiation therapy,” explained lead author Jonathan David Tward, MD, PhD, of the Huntsman Cancer Institute at the University of Utah, speaking at the 2021 Genitourinary Cancers Symposium.
“There are many viable treatment paths for men with prostate cancer,” said Dr. Tward. “These new data may help to distinguish the most appropriate personalized treatment path for patients based on how their specific tumor is behaving. For some men, this means being able to avoid overtreatment with therapies such as hormone therapy, which can momentously impact their quality of life, while still appropriately treating their prostate cancer.”
Jonathan David Tward, MD, PhD
The CCR score is a validated model that combines the cell-cycle progression (CCP) score from the Prolaris assay with the University of California, San Francisco, Cancer of the Prostate Risk Assessment (CAPRA) score (see below). A score based on clinical characteristics and cell-cycle proliferation gene expression offers accurate prognostic information regarding the 10-year risk of metastasis in patients with intermediate- and high-risk localized prostate cancer.
A previous study with a total of about 718 patients validated a CCR score cutoff of 2.112 to identify patients with lower than a 5% risk of metastasis at 10 years. The validation study, presented by Dr. Tward, had more strictly defined radiation therapy parameters and full data collection on androgen-deprivation therapy use and duration.
The retrospective, multi-institutional study included 741 men with National Comprehensive Cancer Network (NCCN®)-defined intermediate- or high-risk localized prostate cancer treated with radiation therapy or multimodality therapy (androgen-deprivation therapy with radiation therapy).
Radiation therapy was given at a dose equivalent to at least 75.6 Gy at 1.8 Gy per fraction; 84% of patients received at least 79.2 Gy. Androgen-deprivation therapy was combined with radiation in 53% of patients. The median age of study participants was 70 years, and the median CCR score at baseline was 2.1. About half the cohort fell above (371 patients) and below (370 patients) the CCR score threshold.
The median follow-up was 5.9 years. Results showed that the CCR score was prognostic for metastases in patients who received radiation therapy alone and radiation therapy plus androgen-deprivation therapy. Its concordance index was 0.78, which appeared to outperform the CCP score alone (0.69), the CAPRA score alone (0.71), and the NCCN risk groups themselves (0.72).
Patients with CCR scores either below or above the threshold (2.112) had a 10-year risk of metastasis of 4.2% and 25.3%, respectively. For men with scores below the threshold, the 10-year risk of metastasis was 4.2% for radiation therapy alone and 3.9% for radiation plus androgen-deprivation therapy.
“The CCR score is highly precise and accurate as a prognosticator of metastasis,” Dr. Tward said. He explained that the risk of metastasis was below 5% for all NCCN risk groups regardless of androgen-deprivation therapy use. Thus, those risk classifications no longer seem to prognosticate for this outcome below the CCR score threshold.
“The relative risk reduction one would expect by adding androgen-deprivation therapy may not be clinically significant to most patients, given the very low baseline absolute risk,” he said. The 10-year risk below the CCR score threshold was 4.1% overall.
However, the CCR score can be used in discussions with patients. Then, a decision can be made as to whether the benefits of androgen-deprivation therapy are worth the potential side effects and inconvenience. The relative benefit of adding androgen-deprivation therapy to radiotherapy has been proved in many trials, Dr. Tward added. “Nevertheless, this clear relative benefit may become clinically questionable when the baseline risk of metastasis in any population or individual is low.”
DISCLOSURE: Dr. Tward has served as a consultant or advisor to Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Scientific Affairs, Merck, and Myriad Genetics; has received institutional research funding from Bayer and Myriad Genetics; and has provided expert testimony on behalf of Expert Consulting Services.
1. Tward J, Mantz C, Shore N, et al: Association of the clinical cell-cycle risk score with metastasis after radiation therapy and identification of men with prostate cancer who can forgo combined androgen deprivation therapy. 2021 Genitourinary Cancers Symposium. Abstract 195. Presented February 11, 2021.
“The absolute risk reduction in metastasis ranges from 2% to 12% by 10 years. Given this heterogeneity, there is a strong rationale for better prognostic markers to personalize treatment of prostate cancer. Nearly all men treated with androgen-deprivation therapy have variable side effects that...