Perhaps the most promising tool so far is the RNA-based gene-expression cell cycle progression (CCP) score. CCP appears to outperform clinical-factors-based risk stratification for predicting biochemical failure after prostate cancer radiotherapy.6-8 It also appears to predict prostate cancer-specific mortality, and shows promise for identifying patients who need more aggressive radiotherapy.

“A number of biomarkers associated with DNA damage response have also been associated with outcomes following prostate cancer radiotherapy,” Dr Feng and colleagues noted. “This includes the tumor suppressor gene p53, which is prognostic for the development of distant metastases.” Up-regulation of the p53-regulating MDM2 oncogene’s expression predicts metastasis risk and shorter survival time following prostate cancer radiotherapy.


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Before these candidate biomarkers can be translated into routine clinical use for prostate cancer radiotherapy decision-making and planning, however, they require more additional work with larger patient cohorts, experts agree.

Ultimately, predictive biomarkers for prostate cancer radiotherapy will probably be used alongside existing clinicopathologic and biochemical assays and nomograms.

RELATED: GATA2 in Prostate Cancer: A Promising Biomarker

As others have noted for prostate cancer biomarkers in general, most candidate radiogenomic biomarkers are potential prognostic tools that predict patient outcomes regardless of specific treatment strategies. What is needed, Dr Feng and his coauthors argue, are predictive biomarkers associated with outcomes for specific treatment options.

Developing and validating predictive biomarkers are “of paramount importance moving forward,” they argued. 

References

  1. Hall WA, Lawton CA, Jani AB, Pollack A, Feng FY. Biomarkers of outcome in patients with localized prostate cancer treated with radiotherapy. Semin Radiat Oncol. 2016;27:11-20. doi: 10.1016/j.semradonc.2016.09.001
  2. Dinh KT, Muralidhar V, Mahal BA, et al. Occult high-risk disease in clinically low-risk prostate cancer with ≥50% positive biopsy cores: should national guidelines stop calling them low risk? Urology. 2016;87:125-132.
  3. Furlow B. When is IMRT the right treatment for prostate cancer? Oncology Nurse Advisor. https://media.oncologynurseadvisor.com/documents/ 23/ona_radiation0411_5541.pdf. Published 2011. Accessed December, 2016.
  4. Ray ME, Thames HD, Levy LB, et al. PSA nadir predicts biochemical and distant failures after external beam radiotherapy for prostate cancer: a multi-institutional analysis. Int J Radiat Oncol Biol Phys. 2006;64(4):1140-50.
  5. Cavanaugh S, Kupelian PA, Fuller CD, et al. Early prostate-specific antigen (PSA) kinetics following prostate carcinoma radiotherapy: prognostic value of a time-and-PSA threshold model. Cancer. 2004;101(1):96-105.
  6. 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;245-55. doi: 10.1016/S1470-2045(10)70295-3
  7. Freedland SJ, Gerber L, Reid J, et al. Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy. Int J Radiat Oncol Biol Phys. 2013;86(5):848-53. doi: 10.1016/j.ijrobp.2013.04.043
  8. Sommariva S, Tarricone R, Lazzeri M, Ricciardi W, Montorsi F. Prognostic value of the cell cycle progression score in patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;69(1):107-15. doi: 10.1016/j.eururo.2014.11.038