Prostate Cancer Progression May Be Predicted by a Novel Gene Panel

VBCC - February 2015, Vol 6, No 1 - Personalized Medicine
Rosemary Frei, MSc

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 Value-Based Cancer Care. “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.

Related Items
Mutation Testing Encouraged for All Patients with Ovarian Cancer
Charles Bankhead
VBCC - June 2016, Vol 7, No 5 published on June 17, 2016 in Personalized Medicine
ESR1 Mutations Predict Worse Survival in ER-Positive Advanced Breast Cancer
Phoebe Starr
VBCC - June 2016, Vol 7, No 5 published on June 17, 2016 in Personalized Medicine
How Do We Measure Quality in the Age of Precision Medicine? Stakeholder Perspectives
Meg Barbor, MPH
VBCC - May 2016, Vol 7, No 4 published on June 3, 2016 in Personalized Medicine
Genomic Instability Score Predicts Survival in Patients with Ovarian Cancer
Charles Bankhead
VBCC - May 2016, Vol 7, No 4 published on June 3, 2016 in Personalized Medicine
Poor Pregnancy Outcomes Seen in Women with Childhood-Onset SLE
Rosemary Frei, MSc
VBCR - April 2016, Vol 5, No 2 published on May 23, 2016 in Canadian Rheumatology Association Annual Meeting
Addressing Undertreatment of Patients with Gout Using EMR Data
Rosemary Frei, MSc
VBCR - April 2016, Vol 5, No 2 published on May 11, 2016 in Canadian Rheumatology Association Annual Meeting
Six-Month OBSErve Study Results Indicate Positive Effects of Belimumab in SLE
Rosemary Frei, MSc
VBCR - April 2016, Vol 5, No 2 published on May 8, 2016 in Canadian Rheumatology Association Annual Meeting
Improvements Needed in Access to Timely Quality Care
Rosemary Frei, MSc
VBCR - April 2016, Vol 5, No 2 published on May 7, 2016 in Canadian Rheumatology Association Annual Meeting
Orthotics Reduce Foot Pain in Juvenile Idiopathic Arthritis
Rosemary Frei, MSc
VBCR - April 2016, Vol 5, No 2 published on May 4, 2016 in Juvenile Idiopathic Arthritis
Genomics May Explain Poor Survival of African Americans with Kidney Cancer
Phoebe Starr
VBCC - April 2016, Vol 7, No 3 published on April 21, 2016 in Personalized Medicine
Last modified: February 19, 2015
  • Rheumatology Practice Management
  • American Health & Drug Benefits
  • Value-Based Cancer Care
  • Value-Based Care in Myeloma
  • Value-Based Care in Neurology