Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy, by Stephen J. Freedland, MD

BERKELEY, CA (UroToday.com) - Many of these studies typically will start with radical prostatectomy tissue because there is plenty of tissue available to look at for genomic predictors of outcome. Next you go back to the biopsy samples and show that the biopsy correlates with the prostatectomy or if it correlates with biopsy upstaging/upgrading, and try to make a leap. We took a little different approach in our study. We said, 'let’s look at patients who underwent external beam radiation therapy.' These men will never undergo prostatectomy, so you will never have more tissue than they have in the biopsy. We wanted to see if the test by Myriad Genetics, the Prolaris Cell Cycle Progression Score (CCP score), could predict survival outcome, after radiation therapy, based on the biopsy. The uniqueness is using the biopsy, not many places are there yet but they want to get there.

When looking at our radiation cohort, which is relatively novel, we found that the CCP score was a very strong predictor of poor outcome, even after adjusting for PSA and Gleason score.

We could think of using this for selecting high-risk patients who do want radiation; we would use the CCP score to particularly predict early biochemical recurrences, which we know are more likely to be metastatic and high-risk and that will ultimately lead to the death of the patient. Therefore, you can say that when you take intermediate-risk men who have a high CCP score, they are going to get hormonal therapy for 6 months or longer. If they have a low CCP score, we are still going to treat them, but they can avoid hormones and the side effects and the toxicity.

There are more opportunities for these molecular markers to integrate themselves besides AS. In our study, about half of the study population was African-American (57%), so this is the first study that I am aware of, at least for the CCP score, that shows that it predicts the outcome in a predominantly African-American cohort. So there are a couple of novel aspects to our study. It really shows the robustness of the CCP score as a predictor of prostate cancer progression. I am not saying that other companies are not showing similar results, but this is what we have worked with and it seems to be working well, and it is a robust test.

Click HERE to view the poster from this session 

Click HERE to read a related interview with Stephen J. Freedland, MD, one of the authors of the study 

 

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freedlandStephen J. Freedland, MD is associate professor of surgery and associate professor in pathology in the Department of Urology at Duke University Medical Center in Durham, NC USA.

He received his MD degree at the University of California–Davis School of Medicine, and went on to complete residencies (in general surgery and urology) at the University of California–Los Angeles Medical Center and a fellowship in urologic oncology at Johns Hopkins Hospital.

His clinical interests include prostate cancer; benign prostatic hyperplasia, and other prostate diseases; GreenLight laser prostatectomy; radical prostatectomy; and TURP.

His research focuses on prostate cancer, obesity, nutrition, diet, PSA, biomarkers, and statistical modeling.

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ABSTRACT:

Moderated Poster: Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy

Stephen Freedland, Leah Gerber, Julia Reid, William Welbourn, Eliso Tikishvili, Jimmy Park, Abid Younus, Alexander Gutin, Zaina Sangale, Jerry Lanchbury, Joseph Salama, and Steven Stone

Introduction and Objectives: Accurate risk stratification improves decision making in localized prostate cancer. The CCP score, a prognostic RNA signature based on the average expression level of 31 cell cycle progression (CCP) genes, was developed to aid in this task. Previously, the CCP score was shown to be predictive of biochemical recurrence (BCR) after prostatectomy, and prostate cancer specific mortality in men undergoing observation. However, the value of CCP score in men undergoing primary electron beam radiation therapy (EBRT) was untested.

Methods: The CCP score was derived retrospectively from the diagnostic biopsy of 141 patients treated with EBRT at the Durham VA medical Center. Inclusion criteria were disease diagnosis from 1991 to 2006 and available biopsy tissue. Approximately half of the cohort was African-American. Outcome was time from EBRT to BCR using Phoenix definition, and median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by CoxPH survival analysis and likelihood ratio tests.

Results: Patient data were censored at 5-years of follow-up and 19 patients (13%) had BCR. The median CCP score was 0.12(IQR -0.43 to 0.66). In univariable analysis, CCP score was a significant prognostic variable (p-value = 0.0017). The hazard ratio (HR) for BCR was 2.55 (95% CI (1.43, 4.55)) for a one-unit increase in CCP score (equivalent to a doubling of gene expression). In a predefined multivariable analysis that included Gleason score, PSA, and percent positive cores, the HR for CCP changed only marginally and remained significant (HR per CCP unit 2.09 (95% CI (1.05, 4.18), p-value = 0.035), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. Further adjustment for hormonal therapy or radiation dose did not materially alter this association. The score was also associated with prostate cancer specific mortality. There was no evidence for interaction between CCP and any clinical variable, including ethnicity.

Conclusions: In a cohort of men treated with EBRT, the CCP score was significantly associated with outcome and provided prognostic information beyond what was available from clinical parameters. If validated in a larger cohort, CCP score could be used to select high-risk men undergoing EBRT who may need combination therapy for their clinically localized prostate cancer.

Sources of Funding: Myriad Genetics