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A Genomic Test Can Help Predict Outcomes in Men With Prostate Cancer

National Cancer Centre Singapore and Canada’s Princess Margaret Cancer Centre research findings show that a genomic test may help guide use of hormonal therapy with radiotherapy in prostate cancer.

A novel study by the National Cancer Centre Singapore (NCCS) and Canada’s Princess Margaret Cancer Centre, has found that a commercially available genomic test can help to predict outcomes in men with localised prostate cancer.

The genomic test named “Decipher” can identify patients who may be treated successfully with radiotherapy alone.

This could potentially spare patients from a course of hormonal therapy, which can cause side effects such as ischemic heart disease, stroke, metabolic syndrome and dementia.

Additionally, they found that the test was more accurate in identifying patients with lethal prostate cancer, who may benefit from combination systemic therapy and radiotherapy.

With this finding, NCCS plans to validate the test in local patients, and ultimately use it to improve patient risk stratification and design bespoke precision strategies in the treatment of localised prostate cancer in Singapore.

Presently, patients are identified for the combined therapy through a classification system endorsed by the US National Comprehensive Cancer Network (NCCN) guidelines. The system classifies intermediate-risk prostate cancer patients into ‘favourable’ and ‘unfavourable’ subgroups.

Those in the ‘unfavourable’ subgroup are more susceptible to metastatic relapse (cancer recurrence in the distant organs such as liver, lungs, or bones) and death due to prostate cancer. Hence, it is recommended that hormonal therapy is combined with radiotherapy to reduce risk of distant metastasis in these patients.

However, the NCCN criteria remains imprecise, and approximately 30 to 40 per cent of patients with defined as unfavourable intermediate-risk prostate cancer may still be over-treated with combination hormonal-radiotherapy. This would then expose them to side effects they may otherwise avoid.

To improve the current prognostication methods for prostate cancer, the research team worked with Decipher Biosciences using their clinically validated transcriptome-wide expression profiling assay, the Decipher genomic classifier. This assay classifies men into low-, intermediate- and high-risk for metastasis based on a risk score generated from 22 genes. The Decipher test has been shown in multiple prostate cancer cohorts to predict for lethal relapse following surgery, and these men may benefit from early radiotherapy for salvage treatment. However, it has not been previously studied using diagnostic biopsies from men treated with radiotherapy alone.

In this study, the team performed Decipher testing on biopsies of 121 patients with intermediate-risk prostate cancer treated with high-dose radiation therapy alone. After seven years of follow-up, the overall relapse rate in this group was low, at 15 per cent (24 PSA relapse events). The study cohort comprised of 33 patients classified as ‘favourable’ and 87 patients classified as ‘unfavourable’ by the NCCN classification system.

Decipher reclassified a high proportion of these men (N = 60 of 87) from ‘unfavourable’ to ‘low-risk’ by the Decipher score. When correlated to the relapse rates of these men, Decipher was substantially more accurate than the clinical staging system; with an accuracy of 86 per cent compared to 54 per cent, respectively. Impressively, when the NCCN clinical staging system and Decipher were combined, the accuracy of identifying men with truly high-risk prostate cancer was 89 per cent. These findings, therefore, support the use of hormonal therapy with radiotherapy in these intermediate-risk prostate cancer patients who are Decipher ‘high-risk’.

“This study highlights the added benefit of molecular diagnostics in the era of precision cancer care. Particularly in prostate cancer patients, the study argues for the push to bring well-validated tests into the clinic, so as to improve our current method of risk assessment of these men,” explains Dr Melvin Chua, a senior consultant radiation oncologist at the NCCS. He is also one of the Principal Investigators and a co-Senior author of this multi-centre collaboration.

Decipher testing is commercially available in the United States. NCCS will be collaborating with Decipher Biosciences to enable use of this technology in NCCS’ laboratories.

The findings of this study were published in the Red Journal (International Journal of Radiation Oncology Biology and Physics). [APBN]