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Blood Test Differentiates Men Who May Gain From Targeted Prostate Cancer Treatment

NEW YORK (GenomeWeb) – UK researchers have developed a blood test to differentiate men with prostate cancer who may benefit from targeted treatments.

In a cohort of some 265 men with advanced prostate cancer, researchers led by Gerhardt Attard from the Institute of Cancer Research gauged the number of copies of the androgen receptor gene that the men had in tumor DNA circulating in their blood, and correlated that with their survival. The androgen receptor is known to be involved in developing resistance to the standard abiraterone and enzalutamide treatments.

As they reported yesterday in the Annals of Oncology, the researchers found that their droplet digital PCR test could quantify AR status from blood samples and that men with AR gains had both worse overall survival and progression-free survival. The patients were treated with either abiraterone or enzalutamide before or after docetaxel chemotherapy.

"We have developed a robust test that can be used in the clinic to pick out which men with advanced prostate cancer are likely to respond to abiraterone and enzalutamide, and which men might need alternative treatments," Attard said in a statement.

He and his colleagues optimized a multiplex ddPCR assay that included four reference genes to pick up AR copy number from within patient blood samples.

For a portion of the patients in their primary cohort — 171 men who began treatment with abiraterone or enzalutamide before docetaxel chemotherapy and 98 who had abiraterone or enzalutamide after chemotherapy — the researchers had both ddPCR assay data as well as next-generation sequencing data. Results from both showed a strong agreement on copy number as well as on AR mutation allelic frequency. No mutations were detected by one approach but not by the other, they reported.

They also noted that the prevalence of plasma AR aberrations was higher in men who had already undergone chemotherapy.

In that primary cohort, the researchers further found that plasma AR copy number gain was associated with shorter overall outcome as well as with shorter progression-free survival in both patients who had undergone chemotherapy as well as those who had not undergone chemotherapy. Men with multiple copies of the AR gene were nearly four times more likely to die during the course of the study.

They replicated this finding in a separate cohort of 94 men from whom plasma was obtained prior to enzalutamide treatment, and, again, AR gain was significantly associated with shorter overall survival.

According to the researchers, a ddPCR assay like theirs could be easily incorporated into in a clinical lab service.

"Our method costs less than £50 [US $64], is quick to provide results, and can be implemented in hospital laboratories across the [National Health Service]," Attard added. "We are now looking to assess our test in prospective clinical trials and would hope it can become part of standard patient care."

They noted, however, that their test does not control for plasma DNA content, which could introduce some bias. Additionally, the cohort size in this study was small and to be able to change treatment practices, the researchers said that the study would have to be replicated in a larger population.