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Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort.

Publication ,  Journal Article
Cooperberg, MR; Simko, JP; Cowan, JE; Reid, JE; Djalilvand, A; Bhatnagar, S; Gutin, A; Lanchbury, JS; Swanson, GP; Stone, S; Carroll, PR
Published in: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
April 2013

We aimed to validate a previously described genetic risk score, denoted the cell-cycle progression (CCP) score, in predicting contemporary radical prostatectomy (RP) outcomes.RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. Recurrence was defined as two prostate-specific antigen levels ≥ 0.2 ng/mL or any salvage treatment. Associations between CCP score and recurrence were examined, with adjustment for clinical and pathologic variables using Cox proportional hazards regression and partial likelihood ratio tests. The CCP score was assessed for independent prognostic utility beyond a standard postoperative risk assessment (Cancer of the Prostate Risk Assessment post-Surgical [CAPRA-S] score), and a score combining CAPRA-S and CCP was validated.Eighty-two (19.9%) of 413 men experienced recurrence. The hazard ratio (HR) for each unit increase in CCP score (range, -1.62 to 2.16) was 2.1 (95% CI, 1.6 to 2.9); with adjustment for CAPRA-S, the HR was 1.7 (95% CI, 1.3 to 2.4). The score was able to substratify patients with low clinical risk as defined by CAPRA-S ≤ 2 (HR, 2.3; 95% CI, 1.4 to 3.7). Combining the CCP and CAPRA-S improved the concordance index for both the overall cohort and low-risk subset; the combined CAPRA-S + CCP score consistently predicted outcomes across the range of clinical risk. This combined score outperformed both individual scores on decision curve analysis.The CCP score was validated to have significant prognostic accuracy after controlling for all available clinical and pathologic data. The score may improve accuracy of risk stratification for men with clinically localized prostate cancer, including those with low-risk disease.

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Published In

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

April 2013

Volume

31

Issue

11

Start / End Page

1428 / 1434

Related Subject Headings

  • Risk Assessment
  • Reproducibility of Results
  • Prostatic Neoplasms
  • Prostatectomy
  • Prostate-Specific Antigen
  • Proportional Hazards Models
  • Outcome Assessment, Health Care
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged
 

Citation

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Cooperberg, M. R., Simko, J. P., Cowan, J. E., Reid, J. E., Djalilvand, A., Bhatnagar, S., … Carroll, P. R. (2013). Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 31(11), 1428–1434. https://doi.org/10.1200/jco.2012.46.4396
Cooperberg, Matthew R., Jeffry P. Simko, Janet E. Cowan, Julia E. Reid, Azita Djalilvand, Satish Bhatnagar, Alexander Gutin, et al. “Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort.Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology 31, no. 11 (April 2013): 1428–34. https://doi.org/10.1200/jco.2012.46.4396.
Cooperberg MR, Simko JP, Cowan JE, Reid JE, Djalilvand A, Bhatnagar S, et al. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013 Apr;31(11):1428–34.
Cooperberg, Matthew R., et al. “Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort.Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, vol. 31, no. 11, Apr. 2013, pp. 1428–34. Epmc, doi:10.1200/jco.2012.46.4396.
Cooperberg MR, Simko JP, Cowan JE, Reid JE, Djalilvand A, Bhatnagar S, Gutin A, Lanchbury JS, Swanson GP, Stone S, Carroll PR. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013 Apr;31(11):1428–1434.

Published In

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

April 2013

Volume

31

Issue

11

Start / End Page

1428 / 1434

Related Subject Headings

  • Risk Assessment
  • Reproducibility of Results
  • Prostatic Neoplasms
  • Prostatectomy
  • Prostate-Specific Antigen
  • Proportional Hazards Models
  • Outcome Assessment, Health Care
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Middle Aged