In a new paper entitled “A molecular signature predictive of indolent prostate cancer”, a research team at Columbia University Medical Center in New York report the identification of a three-gene “signature” that may be able, accurately, to differentiate between indolent and more aggressive forms of prostate cancer.
The paper by Irshad et al. appears in the journal Science Translational Medicine and there is also a media release from the University of Columbia Medical Center. A number of medical news sites have already commented on this new set of findings (see, for example, HealthDay and CancerNetwork.com).
Now we do need to be cautious about the “excitement factor” here. The study is based on analysis of tissue from the biopsy specimens from 43 patients who had been monitored for at least 10 years with active surveillance at Columbia. All the patients had first been diagnosed with low-risk prostate cancer. Of these 43 patients, 14 went on to develop advanced prostate cancer over time, but all 14 were correctly identified by the test by members of the research team who were “blinded” to the actual outcomes of all the patients.
To quote the senior author of this paper, Dr. Cory Abate-Shen:
The bottom line is that, at least in our preliminary trial, we were able to accurately predict which patients with low-risk prostate cancer would develop advanced prostate cancer and which ones would not.
The research team had focused its efforts on genes related to aging, and most particularly on genes known to be affected by “cellular senescence” (a normal process in which older cells cease to divide but remain metabolically active). It had already been recognized that cellular senescence can be important to tumor suppression in general. The presence of the three genes that they have identified — FGFR1, PMP22, and CDKN1A — appears to be able to predict the 10-year outcome of men diagnosed with low-risk prostate cancer. Tumors that test negative for the full three-gene biomarker appear to be clinically aggressive.
Quoted in the commentary on the CancerNetwork.org web site, Dr. Eric Klein of the Cleveland Clinic, states that:
To focus on senescence genes is intellectually interesting. There is already a body of work supporting the role of these genes in prostate cancer, but to my knowledge no one has looked at them in early-stage disease before.
Dr. Klein is also quoted as follows:
These types of markers will, for the first time, give us the opportunity to measure biological features of cancer in the same patient, with multiple biopsies spread out over many years.
Apparently, another trial is already underway at Columbia to validate these initial findings, and some type of national trial to complete the validation process is in the planning stage. This could be a really clinically important finding for the future management of prostate cancer. It might well allow us to identify the patients who really do not need aggressive treatment at all, but can just be monitored over time. It wouldn’t eliminate the need for biopsies, but it might allow us to truly “uncouple” the process of diagnosis from treatment for tens of thousands of men, every single year.