Prostate Cancer Progression May Be Predicted by a Novel Gene Panel

A novel gene panel is showing promise for determining which treatment-naïve patients with prostate cancer could benefit from intensified treatment. A new study indicates that a 100-gene-loci panel can identify which patients with prostate cancer are most likely to fail treatment within 18 months, with a multivariable analysis yielding a hazard ratio of 2.9 for relapse (Lalonde E, et al. Lancet Oncol. 2014;15:1521-1532).

The study was not powered to analyze cancer-specific mortality and overall survival. However, its results will be the basis for further analyses of the impact of adjuvant treatment on the DNA panel’s performance.

“We will be culling out patients with the gene signature into novel clinical trials that will compare adjuvant treatment versus no adjuvant treatment, with the end point being biochemical failure at 18 months and local control, using postradiotherapy biopsies,” lead investigator Robert G. Bristow, MD, PhD, clinician scientist at Princess Margaret Cancer Centre, Toronto, Ontario, Canada, told Urology Practice Management. “If the intensified treatment is more successful than the standard treatment for signature-positive patients, then our prognostic signature turns into a predictive signature.”

Dr Bristow; colead investigator Paul C. Boutros, PhD, of the Ontario Institute for Cancer Research, Toronto; and their coinvestigators, first extracted DNA from 126 preradiotherapy biopsies from patients with low or intermediate risk for prostate cancer progression.

They identified 4 distinct genetic profiles or subtypes based on the resulting gene-alteration panel. Patients with subtype 4 had an 89% 5-year biochemical relapse-free survival rate compared with 53% to 58% rates for the other 3 subtypes. The team also determined that the test’s prognostic power comes from the presence of specific gene alterations and general genomic instability.

Furthermore, tissue hypoxia, which had already been well-established as linked to worse prognosis, is associated with accuracy of the genomic panel. Patients with a high proportion of gene alteration and high hypoxia had the worse prognosis, whereas those with only high hypoxia did well after radical prostatectomy.

The researchers then created the 100-loci DNA signature and validated its ability to identify patients at risk for cancer progression using radical prostatectomy samples from patients treated at Memorial Sloan Kettering Cancer Center (MSKCC) and in Cambridge, United Kingdom.

The hazard ratio for biochemical relapse was 2.8 among patients with a Gleason score of 7. The gene panel was also highly prognostic for low-risk patients and those who went on to develop metastases; for example, 89% of low- to intermediate-risk patients at MSKCC who were classified by the gene panel as having a good prognosis were relapse free at 5 years compared with 58% of those who were classified as having a poor prognosis.

Further validation yielded a 2.9 hazard ratio for progression in patients deemed by the gene panel to have a poor prognosis versus those with a good prognosis.

The team also found that the genomic signature provided better prognostication than 23 RNA panels that had been previously investigated by other researchers.

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