Many men with prostate cancer have slow-growing tumors that don't require aggressive treatments such as surgery or radiation therapy, whereas others have rapidly-growing prostate tumors that are life threatening. Distinguishing between these patients with indolent versus aggressive disease is a major challenge, but researchers have just made a significant step towards identifying genetic risk factors for prostate cancer prognosis.
A multi-institutional research team has identified three distinct molecular subtypes of prostate cancer, which are correlated with survival rates and may help guide future treatment planning. Their study results were presented at the annual meeting of the American Society of Radiation Oncology by Daniel Spratt, MD, an assistant professor in radiation oncology at the University of Michigan Heath System.
Spratt explained in a recent American Society of Radiation Oncology press release:
Tumors that appear similar under a microscope can behave very differently, from a clinical standpoint. One promise of genomic analyses is to elucidate subtypes of cancer based on the genetics of the tumor rather than merely how they look or what size they are.
The research team analyzed the RNA expression patterns of 4,236 primary prostate cancer samples taken from nine independent groups of men, who had their prostate surgically removed to treat primary prostate cancer. The investigators' statistical clustering analysis identified three distinct patient groups based on 100 key genes, which they named the Prostate Cancer 100. These study results were then validated using samples from over 2,100 patients.
The subtypes were found to be correlated with androgen receptor activity, ERG oncogene expression and other factors known to promote prostate tumor growth. They were also correlated with how long patients survived without metastasis. The distant metastasis-free survival rates varied among the three subgroups -- 73.6 percent for group A, 64.4 percent for group B and 57.1 percent for group C -- showing that subtype A patients had the most favorable prognosis.
Furthermore, the study found that subtype B and C patients responded significantly better to postoperative radiation therapy, which was used after the prostate was surgically removed in order to kill any remaining cancer cells. This is important because radiation therapy has many potential side effects, including impotence and incontinence.
Spratt summarized in the press release:
We believe that these subtypes reflect truly distinctive underlying biology and that this work represents a significant advance in our understanding of prostate cancer biology. Moreover, our findings identify numerous genes and enriched biologically active pathways in prostate cancer that have been underappreciated to date but may be potential targets to improve cure rates in this disease by developing new targeted therapies.
Previously: Genetic testing and its role in women's health and cancer screening, Stanford experts talk new diagnostic technology for prostate cancer and Managing a prostate cancer diagnosis: From leader to follower, and back again
Photograph by Raul654
