Blood test can guide treatment for most aggressive prostate cancer

Heidi Fettke

School of Clinical Sciences at Monash Health (SCS) researcher Heidi Fettke and A/Prof Arun Azad from Peter MacCallum Cancer Centre, in collaboration with Chris O’Brien Lifehouse, have developed a simple blood test that can show which men with the most aggressive type of prostate cancer should respond to conventional therapy, and those who need other options. 

The team joined forces with California-based biotechnology company, Predicine, to apply a first-in-class liquid biopsy for men with metastatic castration-resistant prostate cancer (mCRPC).

SCS researcher and lead author Heidi Fettke said, "Historically, it has been very difficult to profile metastatic prostate cancer due to difficulties with accessing up-to-date tumour tissue. With this research we hope to make the analysis of blood-based biomarkers a suitable alternative to conventional biopsies, and to better guide therapy in aggressive prostate cancer."

Media release: Peter MacCallum Cancer Centre

From as little as 10ml of blood, the test can simultaneously profile the circulating DNA and RNA which is shed by cancer cells, offering important insights into the make-up of the cancer and treatments most likely work.

Nearly 20,000 men are diagnosed with prostate cancer every year in Australia, making up a quarter of all male cancer diagnoses, and mCRPC is the most aggressive form accounting for over 3000 deaths from this disease every year.

Metastatic prostate cancer has spread beyond the prostate, and it is “castration-resistant” if progression continues despite the patient starting therapy that deprives the cancer of androgen hormones, such as testosterone.

“While advances in therapeutic strategies have significantly improved quantity and quality of life for men with mCRPC, there remains a pressing need to find predictive and prognostic biomarkers,” explains A/Prof Arun Azad, senior author on the study and medical oncologist at Peter Mac.

“These blood tests, also called liquid biopsies, have emerged as a minimally-invasive alternative to conventional biopsy for interrogating the prostate tumour genome.

“Liquid biopsies have demonstrated strong congruence with tumour biopsies, whilst simultaneously encapsulating the genomic complexity often seen in mCRPC.

”In this study, published in the journal European Urology, researchers applied Predicine’s cell-free DNA and cell-free RNA next generation sequencing liquid biopsy technology to detect whether changes to the Androgen Receptor (AR) gene have occurred within mCRPCs.

They used this to test the blood of Australian men with mCRPC prior to treatment, accurately detecting some form of AR alteration in over half of patients.

“We found that abnormalities in the AR gene detected in the blood of men with advanced prostate cancer were associated with poor responses to available drug treatments and reduced survival,” says A/Prof Azad.

This information could be used to better guide treatment of advanced prostate cancer.”

“A simple test to detect AR abnormalities would help doctors determine optimal treatment selection, better design innovative clinical trials, and aid in discussions with patients and caregivers around realistic and expected outcomes.

The study results were further validated in a second cohort of prostate cancer patients in the United States.

The new liquid biopsy test from Predicine is also more informative than previous tests as it analyses two types of genetic material – DNA and RNA – to give a more in-depth and accurate insight into AR abnormalities within the cancer.

Reference

Heidi Fettke et. al. Combined Cell-free DNA and RNA Profiling of the Androgen Receptor: Clinical Utility of a Novel Multianalyte Liquid Biopsy Assay for Metastatic Prostate Cancer. European Urology DOI: https://doi.org/10.1016/j.eururo.2020.03.044