Study: Test score may predict which prostate cancer patients can safely skip combined therapy

IN-DEPTH REVIEW OF RESEARCH

Study background

The NCCN and other professional societies recommend that men with aggressive prostate cancer be treated with combined therapy rather than a single-therapy treatment. Although combined therapy can reduce the risk of recurrence and cancer spread (metastasis), these treatments also increase the risk of illness and death due to the treatment. In addition, combined therapy may not be necessary for all men. Methods are needed to identify men with a higher risk of disease progression who could benefit from combined therapy and those with lower risk who may safely avoid it.

Doctors can determine how aggressive prostate cancer is with a tumor test called a cell cycle progression (CCP) test. Prior research has shown that combining a CCP tumor test with a patient's medical information into an overall score called a clinical cell cycle risk (CCR ) score is a more effective way to determine the risk of progressive prostate cancer.

Researchers wanted to know how well their CCR test (called Prolaris) works for predicting outcomes for men with intermediate or high-risk prostate cancer. This score is a combination of scores from two tests, Myriad Genetics cell-cycle progression (CCP) tumor test and the University of California San Francisco Cancer of the Prostate Risk Assessment (CAPRA), which combines several clinical tests, including the Gleason score, baseline PSA levels and tumor stage.

Researchers of this study wanted to know

Researchers of this study wanted to know if CCR scores can identify which patients will benefit from combined therapy for prostate cancer and which patients could safely forgo combined therapy.

Populations looked at in this study

Study participants included 718 men with prostate cancer who were previously treated at one of five medical centers throughout the United States. A group of 624 (87 percent) patients had intermediate cancer  or high-risk cancer based on NCCN criteria (471 patients had intermediate and 153 patients  had high-risk cancer)

The men had either single-therapy cancer treatment (e.g., radiation alone, or surgery without adjuvant radiation or androgen deprivation therapy) or combined-therapy treatment (e.g., combined radiation and ADT, or surgery with adjuvant radiation, ADT or the combination.)

Study design

This was a retrospective study. Researchers analyzed past medical history that included prostate cancer type, the treatment used, cancer outcomes and CCR scores. All patient records included at least 10 years of medical history after cancer treatment. Researchers asked whether using a predetermined CCR score threshold of 2.112 (defined from a previous study) effectively predicted which patients’ cancers would progress or metastasize within 10 years of initial treatment. They also grouped patients' information depending on whether they had single therapy or combined therapy for further analyses.

Study findings

Study findings showed that:

• Among men who underwent single therapy, those with CCR scores above the threshold of 2.112 had a nearly 16-fold greater risk of metastasis than men with CCR scores below 2.112.
  • 4.3% of men with a CCR score below 2.1 developed metastasis within 10 years compared to 20.4% of men with scores above that threshold.
  • 23% of men with a CCR score below 2.1 had cancer progression within 5 years compared to 52% in men with scores above that threshold.
• In men with scores above the threshold, combined therapy reduced the predicted risk of metastasis, but only up to a CCR score of 4.1.
• Based on the CCR score threshold and individual CCR scores, the researchers calculated that 27% of men with high-risk disease and 73% with unfavorable intermediate cancer might be able to avoid combined-therapy cancer treatment.

Strengths and limitations

Strengths

• The scores were derived from several readily available tests that combine tumor testing information with medical information into a single more comprehensive measure. 
• This study validated the use of a CCR threshold that has the potential to inform treatment decision-making for men with intermediate or advanced prostate cancer.
• The was a large study that included information from more than 700 men from multiple sites in the United States.
• The study was diverse, consisting of 73.8% men who identified as White, 25.5% who identified as African American and 0.7% who identified as other races.
• The statistics performed in this study support the conclusions.

Limitations

• This study was funded by Myriad Genetics, the laboratory that performs this particular CCP test, which is one part of the CCR score. In all cases, the CCP tests for the enrolled men had been completed prior to this study and were part of the patients’ medical records. Future independent studies are needed to validate this data.
• Much of the study’s focus was on men with intermediate or high-risk prostate cancer based on NCCN criteria. Men with low-risk prostate cancer (13% of all prostate cancers) were not included.
• The study did not distinguish average CCR scores by prostate cancer type, although that information would have been helpful. For example, that might provide insight into how CCR scores in men with low-risk prostate cancer differ from those with intermediate or high-risk disease.
• The study provided little detail on the length of cancer treatments, which may affect treatment outcomes.
• This was a retrospective study looking at past information. All men in the study had known outcomes 10 years after treatment.  (This contrasts to a prospective study where treatment would be known. However, most prospective studies take a long time to produce results.)
• The study does not establish that the approach of tailoring therapy based on the CCR should be standard of care but provides the rationale to perform studies to show whether that approach is safe and improves outcomes.

Context

The NCCN recommends that men with intermediate or high-risk prostate cancer undergo combined-therapy (e.g., radiation and ADT, or surgery with adjuvant radiation, ADT or the combination of all 3 treatments) to reduce the risk of metastasis. Combined therapy is often associated with higher costs, reduced quality of life during treatment and more side effects than treatment with single-therapy treatment. This study shows that setting a threshold score for CCR, which estimates prognosis, may help to identify men who can avoid combined therapy and safely receive single-therapy treatment.

Conclusions

Prognostic risk estimator tests such as CCR provide information about the potential for cancer to progress independent of the treatment given. Based on the study findings, a threshold CCR score may be able to predict which men with prostate cancer may benefit from recommended combined therapy (those with CCR scores above the threshold) and men who may be able to avoid it (those with CCR scores below the threshold). More independent studies are needed to confirm the reliability of the CCR thresholds used in this study before they can be used to guide treatment decisions. If validated, the current findings may help men with prostate cancer and their doctors make more accurate and informed treatment decisions based on a patient’s individual CCR score.

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posted 7/9/21