Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy - PubMed (original) (raw)

. 2013 Aug 1;86(5):848-53.

doi: 10.1016/j.ijrobp.2013.04.043. Epub 2013 Jun 5.

Leah Gerber, Julia Reid, William Welbourn, Eliso Tikishvili, Jimmy Park, Adib Younus, Alexander Gutin, Zaina Sangale, Jerry S Lanchbury, Joseph K Salama, Steven Stone

Affiliations

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

Stephen J Freedland et al. Int J Radiat Oncol Biol Phys. 2013.

Abstract

Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy.

Methods and materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests.

Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity.

Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

Published by Elsevier Inc.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest Notification

A potential conflict of interest does exist since employees of Myriad Genetics, Inc. have received salary and stock from Myriad Genetics, Inc. The other authors, not employed by Myriad Genetics, Inc., do not have a conflict of interest since they have not received payment from Myriad Genetics, Inc.

Figures

Figure 1

Figure 1

Distribution of CCP scores. A) Distribution in entire cohort. Red tick marks indicate the 25th (Q1, −0.43), the median (Q2, 0.12), and 75th (Q3, 0.66) percentile of score values. B) CCP score distribution stratified by ethnicity.

Figure 2

Figure 2

Kaplan-Meier for 5-year recurrence free survival illustrating the effect of a one-unit increase in CCP score (also equivalent to a doubling in gene expression levels).

Figure 3

Figure 3

Scatter plot of the 5-year predicted risk of BCR for a model including CCP score (x-axis) versus clinical parameters only (y-axis). Patient’s Gleason score is indicated by dot color. For any given patient, the added contribution of the CCP score to the predicted risk, based on Gleason, PSA, percent positive cores, and concurrent ADT, can be determined by the horizontal distance between the dot and the diagonal dashed line.

Comment in

Similar articles

Cited by

References

    1. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367:203–213. - PMC - PubMed
    1. Roach M, 3rd, Waldman F, Pollack A. Predictive models in external beam radiotherapy for clinically localized prostate cancer. Cancer. 2009;115:3112–3120. - PMC - PubMed
    1. Hurwitz MD, Halabi S, Archer L, et al. Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: Long-term results of calgb 99809. Cancer. 2011;117:5579–5588. - PMC - PubMed
    1. Cuzick J, Swanson GP, Fisher G, et al. Prognostic value of an rna expression signature derived from cell cycle proliferation genes in patients with prostate cancer: A retrospective study. Lancet Oncol. 2011;12:245–255. - PMC - PubMed
    1. Cuzick J, Berney DM, Fisher G, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. 2012;106:1095–1099. - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources