New study finds genetic anomalies in advanced prostate cancer patients

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A new study carried out by a collaboration of international research teams shows genetic anomalies in biopsy samples from patients with advanced prostate cancer through a large multi-institutional integrative clinical sequencing approach. The study was published in the journal Cell and is called “Integrative Clinical Genomics of Advanced Prostate Cancer”.

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Prostate cancer key statistics:

  • Prostate cancer is the second most common cancer in American men, other than skin cancer. 
  • Prostate cancer is the second leading cause of cancer deaths in men. 
  • About 1 in 7 men will be diagnosed with prostate cancer in their lifetime. 
  • The average age of diagnosis is 66. 
  • Prostate cancer is very rare in men younger than 40, but the risk of developing prostate cancer significantly increases after age 50. About 6 in 10 cases of prostate cancer are found in men over the age of 65.
  • It is estimated that in 2015, there will be about 220,800 new cases of prostate cancer diagnosed. 
  • African American men are 70 percent more likely to be diagnosed with prostate cancer.
  • Having a father or brother with prostate cancer more than doubles a man’s risk of developing the disease. The risk is much higher for men with multiple relatives with a history of the disease.
  • Obesity and metabolic syndrome can increase risk by 57 percent; they can also mean increased prostate cancer tumor volume and recovery risks.
  • For now, the PSA test is the best way to establish a prostate health baseline; men should have a baseline PSA test starting at age 40.
  • Robotic prostate surgery remains a leading treatment option, with highly successful recovery and quality of life results when performed by an experienced surgeon.

Studies in the past have looked at the genomic characterization of clinically localized prostate cancer. However, they have only found a few genomic alterations. This new research gathered 150 men with metastatic castration-resistant prostate cancer and sequenced the DNA and RNA of biopsy samples from them. Metastatic castration-resistant prostate cancer is an advanced form of prostate cancer that is no longer responds to regular hormone therapy. This study is the first to conduct a major analysis of this aggressive cancer in a clinical context.

Researchers found that ‘almost all the tumor samples analyzed had a genetic anomaly known to promote cancer development.’ The most common anomaly found was in the androgen receptor which was present in almost two-thirds of the patients. The researchers were not surprised to find this as castration-resistant prostate cancers are non-responsive to conventional androgen-blocking therapies. BRCA1 or BRCA2 gene mutations were found in 14 percent of the patients. These type of mutations are known to be linked to a higher risk of breast and ovarian cancer. Additionally, 8 percent of the patients had an inherited genetic alteration and 23 percent anomalies in DNA repair pathways.

According to Dr. Arul Chinnaiyan from the University of Michigan Health System who is one of the study’s co-senior authors and co-leader of the Stand Up to Cancer-Prostate Cancer Foundation Dream Team, “One of the surprising findings in this study was that approximately 90 percent of cases harbored some kind of genetic anomaly that was clinically actionable, meaning we have potential treatments to target that specific aberration. This suggests that clinical genomic sequencing could impact treatment decisions in a significant number of patients with disease.”

The study’s co-senior author Dr. Charles L. Sawyers who is from the Memorial Sloan-Kettering Cancer Center and is the co-leader of the Stand Up to Cancer-Prostate Cancer Foundation Dream Team said, “This multi-institutional and international study demonstrates the feasibility of comprehensive and integrative genomics on prospective biopsies from individual patients to enable precision cancer medicine activities in this large patient population. This study sets the stage for additional profiling efforts which may enable biological discovery and have immediate therapeutic relevance.”

The researchers now plan to sequence and monitor at least 500 patients with advanced prostate cancer. They believe that as androgen receptor mutations and other genetic anomalies are being detected in a large number of patients they will be able to link specific anomalies to the patient’s response or resistance to certain treatments. This will be helpful in the future of treating metastatic castration-resistant prostate cancer.