Prostate Cancer: Unstable Chromosomes May Predict Treatment Failures

Robert G Bristow MD, PhD, FRCPC Clinician-Scientist, Ontario Cancer Institute/Princess Margaret Cancer Centre Professor, Depts. of Radiation Oncology and Medical Biophysics, University of Toronto Director, Core I - STTARR Innovation Facility Canadian Cancer Society Research Scientist MedicalResearch.com Interview with:
Robert G Bristow MD, PhD, FRCPC
Clinician-Scientist, Ontario Cancer Institute/Princess Margaret Cancer Centre
Professor, Depts. of Radiation Oncology and Medical Biophysics, University of Toronto
Director, Core I – STTARR Innovation Facility
Canadian Cancer Society Research Scientist
http://www.uhnres.utoronto.ca/researchers/profile.php?lookup=645

MedicalResearch.com: What are the main findings of the study?

Dr. Bristow: We studied the more than 7 years of outcome of close to 250 patients with localized (intermediate risk) prostate cancer that received precision radiotherapy or surgery for cure. We found that up to one third of these patients fail initial radiotherapy or prostate surgery.

By using a patient’s initial diagnostic core biopsy, we studied the DNA fingerprints of the tumors. We noticed a pattern in which the patients that had failed treatment had abnormal levels of breaks at sites within the chromosomes that are sensitive to DNA damage called, “common fragile sites” (CFS).

These CFS break abnormalities have been linked to cancer in general and usually are associated with instability of the cell’s DNA-a phenomenon that is particularly associated with cancer.

So patients who have unstable chromosomes are more likely to fail precision radiotherapy or surgery.


MedicalResearch.com: Were any of the findings unexpected?

Dr. Bristow: We were surprised by this observation as we thought that patients who have CFS breaks might be more sensitive to radiotherapy-induced DNA damage. And yet we found the opposite.

We now think that the CFS breaks are a signal that the cancer cell has acquired many genetic changes that lead to aggressive cancer cells that can spread early and outside the prostate gland. So our data suggest that the patients failing treatment are due to early metastatic (distant spread) disease.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Bristow: If we validate this study in similar but larger groups of patients, we can develop a test based on CFS breaks in which we can place patients in one of two baskets. Those that do well (the tumor does not have CFS breaks) with local treatment alone (e.g. radiotherapy or surgery) versus those patients who will not do well (the tumor does have CFS breaks) and who, in addition to surgery or radiotherapy, need additional treatments to combat distant spread.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Bristow:
We know need to:

1) Understand further the genetics of a prostate cancer can be measure on a diagnostic biopsy and give information of whether a patient does well or does not do well following precision radiotherapy or surgery for prostate cancer.

2) Develop tests that can score CFS breaks and other genetic factors in a patient’s biopsy to give information as to whether a patient needs treatment intensification (using hormone therapy or chemotherapy or new targeted drugs) beyond the use of precision radiotherapy or surgery, alone.

Citation:

Genomic Instability in Common Fragile Sites (CFSs) is Associated with Less Favorable Outcome in Patients with Intermediate-Risk Prostate Cancer (IR-CaP)

The abstract, “Genomic Instability in Common Fragile Sites (CFSs) is Associated with Less Favorable Outcome in Patients with Intermediate-Risk Prostate Cancer (IR-CaP),” will be presented in detail during a scientific session at ASTRO’s 55th Annual Meeting at 1:00 p.m. Eastern time, on Wednesday, September 25, 2013