Gene Signatures Help Predict Aggressive Prostate Cancer

A whole-blood prognostic test based on gene-expression signatures may help predict risk for patients with castration-resistant prostate cancer (CRPC), reported two recent studies published in The Lancet Oncology.

“We’ve shown it is possible to learn more about prostate cancers by the signs they leave in the blood, allowing us to develop a test that is potentially more accurate than those available now and easier for patients than taking a biopsy,” said Johann S. de Bono, MD, MSc, PhD, leader of the prostate cancer targeted therapy team at The Institute of Cancer Research (ICR).

Researchers at ICR and The Royal Marsden NHS Foundation Trust stratified 94 patients into four groups based on RNA expression profiles that were associated with CRPC. The profiles were created using latent process decomposition (LPD) on whole blood samples that had been hybridized to Affymetrix U133plus2 microarrays and were confirmed by quantitative reverse transcriptase (qRT) polymer chain reaction (PCR).

The four groups were sorted by disease severity as measured by the RNA expression profiles. The first group (LPD1) contained 14 patients with CRPC, while the remaining three groups contained patients with less severe prostate cancer who were being treated by active surveillance.

Patients in the LPD1 group had traits associated with a worse prognosis and a shorter overall survival than patients in the remaining three groups. In the LPD1 group, overall survival was 10.7 months compared to 25.6 months in the remaining three groups (P < .0001). Additionally, the qRT-PCR analysis revealed a nine-gene expression signature that could be used as a prognostic factor for risk stratification.

“Personalized medicine is the future of cancer treatment,” said Martin Gore, MD, PhD, medical director at The Royal Marsden. “This blood test, which reads genetic changes in prostate cancer providing a prediction of how aggressive the cancer might be, is an important development, allowing us to better tailor treatment to suit each individual.”

In the second trial, researchers at the Dana-Farber Cancer Institute and the Memorial Sloan-Kettering Cancer Center enrolled 202 patients with CRPC. A whole blood RNA transcript-based model was used to stratify patients into either a low- or high-risk group based on a six-gene profile assessment.

The median survival was not reached in the low-risk group at 34.9 months but was reached in 7.8 months for those at high-risk (95% CI 1.8-13.9; P < 0.0001). The prognostic ability of the test was further confirmed in an independent cohort.

"There is an urgent need for predictive models that help assess how aggressive the disease is in prostate cancer patients, as survival can vary greatly," said lead investigator William K. Oh, MD, Chief of the Division of Hematology and Medical Oncology of The Tisch Cancer Institute at The Mount Sinai Medical Center. "Our six-gene model, delivered in a simple blood test, will allow clinicians to better determine the course of action for their patients, determine clinical trial eligibility, and lead to more targeted studies in late-stage disease."

Although it was not directly studied on the trial, the six-gene model showed changes in the immune system as a result of advanced CRPC. Further trials will likely examine the predictive capabilities of the blood test as it relates to immunotherapies for prostate cancer, such as sipuleucel-T (Provenge).

Olmos D, Brewer D, Clark J, et al. Prognostic value of blood mRNA expression signatures in castration-resistant prostate cancer: a prospective, two-stage study. [published online ahead of print October 9, 2012]. Lancet Oncol. DOI:10.1016/S1470-2045(12)70372-8.

Ross RW, Galsky MD, Sher HI, et al. A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study. [published online ahead of print October 9, 2012]. Lancet Oncol. DOI:10.1016/S1470-2045(12)70263-2.