Researchers have announced at the 2009 Clinical Congress of the American College of Surgeons that a set of 87 genes one day may be used to routinely determine which patients can be successfully treated for advanced rectal cancer without undergoing a surgical procedure.
The genes were identified in a study of 46 patients who had locally advanced rectal cancer and were far more commonly expressed in patients who had a complete pathological response to chemotherapy and radiotherapy [there were no living cancer cells in a pathologically examined surgical specimen] than those who did not have a pathological response to treatment.
The panel of genes may be the first reliable way of finding patients whose rectal cancer completely responded to chemotherapy and radiotherapy, which precedes an operation in the standard treatment of locally advanced rectal cancer. "We typically say that patients need chemotherapy, radiation therapy, and surgery to get the best outcomes. The upfront chemotherapy and radiation therapy helps shrink tumors down so they can be more easily removed surgically and decreases the chance that the tumor will come back in the pelvis," explained Isabelle Bedrosian, MD, FACS, assistant professor of surgery at the University of Texas M.D. Anderson Cancer Center, Houston.
The combination of preoperative chemotherapy and radiotherapy is also highly effecttive in and of itself. Approximately 20 percent of patients have no signs of rectal cancer after the combination treatment. However, surgeons have not had a way of finding these patients until they operated upon them and removed a surgical specimen for pathological analysis. "Findings from this study suggest that we may have a new tool to say to a patient whose tumor has a specific DNA profile and who has had a complete clinical response to chemotherapy and radiation therapy that he may not need radical surgery," Dr. Bedrosian added.
Researchers from M.D. Anderson Cancer Center are planning to validate findings from this study in an independent data set and then assess whether the genes are able to accurately predict ahead of time which patients will have a pathologically complete response to chemo-radiation. "Once these results have been validated, we can start to explore clinical trials that use the information from the genetic analysis to make decisions regarding patient management. We would propose to take patients who have a positive DNA profile and put them in a study where they don''t undergo surgery. We would follow the patients to see if they have as good cancer-related outcomes as patients who underwent the traditional approach of chemoradio-therapy plus surgery. Our hope is that, in the future, we would be able to show that specific patients who have a complete pathological response, that is those who have complete eradication of the tumor with preoperative chemoradiation, can safely forego surgery," Dr. Bedrosian said.
Qiang Hao; L. Ding; Miguel Rodriguez-Bigas, MD; John M. Skibber, MD, FACS; George J. Change; and Michael D. Story, PhD, also participated in the study.