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

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Contents

At a glance Clinical trials
Study findings Guidelines
Strengths and limitations Questions for your doctor
What does this mean for me? Resources
In-depth  

 

STUDY AT A GLANCE

What is this study about?

This study looked at how well a test score called the combined clinical cell-cycle risk (CCR) score can identify men who may benefit from a single therapy for prostate cancer and men who should consider combined-therapy treatments.

 

Why is this study important?

Prostate cancer treatment

Experts recommend that men with aggressive forms of prostate cancer be treated with combined-therapy (e.g., combined radiation and androgen deprivation therapy [ADT] or surgery with follow-up radiation or ADT) rather than single-therapy treatments (e.g., radiation or surgery alone).

Compared with a single-therapy approach, combined-therapy has been shown to further reduce the spread of prostate cancer. However, combined therapies may lead to more side effects, higher costs and a decreased quality of life. Research shows that combined therapy may not be necessary for all men with prostate cancer.

 

Prognostic tests

Some prostate cancer tests predict the chance that prostate cancer may spread. These tests are known as prognostic tests.

Researchers studied whether a specific prognostic test score, the combined CCR score, can identify which men with prostate cancer would benefit from combined-therapy treatment and which men can safely choose a single therapy. 

 

Study findings

Doctors can use a tumor test called a cell cycle progression (CCP) test to determine the aggressiveness of prostate cancer. 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 accurate way to determine the risk of progressive disease for men with prostate cancer.

Researchers used the Myriad Genetics version of a CCR score called Prolaris, which uses the Myriad CCP tumor test combined with a clinical score using the University of California San Francisco scoring system for clinical information called CAPRA to derive the scores in this study. The researchers tested whether men with a CCR score below 2.1 could forgo receiving combination treatment, while those with a CCR score above 2.1 would benefit from a combination approach.

CCR scores may be useful for deciding if a person will benefit most from a single therapy or combined therapy for prostate cancer.

For this study, researchers used medical data from more than 700 men with advanced prostate cancer. The men were treated at one of five medical centers throughout the United States and had 10 years of followup after their treatment.

Among men who received single-therapy treatment:

  • Those with CCR scores above the threshold of 2.1 were 16 times more likely to develop metastasis than men with CCR scores below 2.1.
  • The authors suggest that men with CCR scores below 2.1 can safely receive only single-therapy treatment (and omit ADT treatment), while men with CCR scores above 2.1 should consider combined-therapy treatment.

Importantly, whether men in this study had an inherited mutation that would increase their risk of aggressive prostate cancer was unknown. Thus, it is not known whether a CCR score could be used for treatment decision-making in men with prostate cancer that is caused by an inherited mutation.

 

Strengths and limitations

Strengths

  • The scores were derived from several readily available tests that combine tumor testing information with medical information in a single, more comprehensive measure. 
  • The study was large and included information from more than 700 men from multiple sites in the United States.
  • The study included a racially diverse group of participants.  
  • The statistics derived in this study support the conclusions.

Limitations

  • This study was funded by Myriad Genetics, the laboratory that performs this particular CCP test that is one part of the CCR score. In all cases, CCR scores for the enrolled men had been provided prior to this study and were part of the patient's 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. However, the study did not look at men at high risk due to an inherited BRCA1 or BRCA2 mutation, which has been linked to aggressive prostate cancer. Nor were men with low-risk prostate cancer included.
  • 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, so researchers could not clarify information that was not included in health records. All men in the study had known outcomes 10 years after treatment.  (This is in contrast to a prospective study where treatment would be known. However, most prospective studies take a long time to produce results.)
  • The approach of changing therapy based on this test has not been prospectively tested in a randomized study but supports the rationale for performing those studies.

 

What does this mean for me?

Overtreating prostate cancer can cause side effects and increase treatment costs. Undertreatment can allow cancer to spread and become life-threatening. The CCR score may help patients and their healthcare providers make more informed decisions about treatment. This study points to the benefit of using a CCR score to identify men whose prostate cancers are most likely to recur and spread and men who may safely skip combined treatment with ADT. Yet, more research is needed to confirm these study results.

It’s important to discuss with your doctor how best to predict the best treatment for your situation.

Share your thoughts on this XRAY review by taking our brief survey.  

posted 7/9/21

 

Reference

Tward J, Schlomm T, Bardot S, et al. Personalizing Localized Prostate Cancer: Validation of a Combined Clinical Cell-cycle Risk (CCR) Score Threshold for Prognosticating Benefit From Multimodality Therapy. Clin Genitourin Cancer. 2021 Jan 19:S1558-7673(21)00013-6. 

 

Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

This article is relevant for:

Men with advanced prostate cancer

This article is also relevant for:

People with prostate cancer

Be part of XRAY:

Expert Guidelines

The National Comprehensive Cancer Network (NCCN) has guidelines for treatment decision-making for people with early-stage prostate cancer, which includes the following.

  • For people with unfavorable intermediate- or high-risk prostate cancer and a life expectancy of 10 years or more, Prolaris or Oncotype DX Prostate testing may be used to help guide cancer treatment decisions. 

Updated: 11/26/2021

Questions to Ask Your Doctor

  • What test will predict the risk of my cancer spreading?
  • What are my options for treating prostate cancer?
  • What side effects may be associated with my treatment?
  • Is taking a combined- (or multi-) therapy approach necessary for my prostate cancer?

Open Clinical Trials

The following are studies enrolling people with early-stage prostate cancer.  

A number of other clinical trials for patients with early-stage prostate can be found here.

Updated: 11/26/2021

Peer Support

The following organizations offer peer support services for people with prostate cance

Updated: 11/26/2021

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.

 

Share your thoughts on this XRAY review by taking our brief survey.
posted 7/9/21

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