Primary tumor resection may be overused in patients with newly diagnosed stage IV colorectal cancer, according to the findings of a new study from The University of Texas MD Anderson Cancer Center.
The retrospective population-based study revealed that among patients diagnosed with stage IV colorectal cancer, annual rates of primary tumor resection decreased substantially between 1988 and 2010, with the largest drops occurring as newer chemotherapy drugs became available in the early 2000s. The study also revealed that survival rates increased in this patient population over roughly the same period.
Role of primary tumor resection
About one in five newly diagnosed colorectal cancer patients has metastatic disease. In some patients with metastatic disease at presentation, primary tumor resection is indicated if primary tumor–related symptoms—such as obstruction, significant bleeding, or perforation—are present. Primary tumor resection is also indicated in the small minority of patients who are eligible for potentially curative resection of both the primary tumor and the distant metastatic disease.
However, the role of primary tumor resection is less clear in the majority of patients, who are asymptomatic at presentation. In patients with metastatic colorectal cancer whose primary tumors are nonobstructive and whose metastatic disease cannot be resected, the National Comprehensive Cancer Network recommends systemic chemotherapy without primary tumor resection. A select but small group of patients may benefit from the surgery as a prophylaxis to prevent primary tumor–related symptoms during chemotherapy. However, noncurative primary tumor resection is associated with morbidity rates of up to 30% and mortality rates of up to 10%. And in many patients with advanced colorectal cancer, noncurative primary tumor resection may in fact preclude the use or delay the start of systemic therapies shown to provide a survival benefit.
“We know that it’s safe to give chemotherapy even with biologics such as bevacizumab to patients with metastatic disease. Yet there’s still controversy about the role of primary tumor resection because of persistent concerns about primary tumor–related complications and because some believe that there’s a survival association,” said George J. Chang, M.D., M.S., an associate professor in the Departments of Surgical Oncology and Health Services Research and the corresponding author of the study’s report. “The purpose of our study was to evaluate the use of primary tumor resection among patients with metastatic colorectal cancer in everyday practice by examining national trends in the proportion of stage IV patients undergoing primary tumor resection.”
New agents bring change
Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results database, Dr. Chang and his colleagues identified more than 64,000 patients who were diagnosed with metastatic colorectal cancer between 1988 and 2010. About two-thirds (67.4%) of these patients underwent primary tumor resection. Factors associated with an increased likelihood of undergoing the surgery included female sex, age less than 50 years, and being married in addition to cancer-related factors such as having colon (rather than rectal) cancer and having a high-grade tumor.
The researchers found that the annual rate of primary tumor resection decreased 17 percentage points between 1988 and 2010, from 74.5% to 57.4%. The most dramatic decreases, which occurred after 2001, coincided with the timing of the U.S. Food and Drug Administration’s approval of a bevy of systemic and biologic therapies for colorectal cancer. These agents—which include irinotecan, oxaliplatin, capecitabine, bevacizumab, cetuximab, and panitumumab—can be used in the first-, second-, or third-line settings with or without fluorouracil and folinic acid to treat the disease. The agents have been found to prolong survival and to be associated with low rates of primary tumor–related complications. In addition, the agents can be used to shrink borderline resectable disease so that it can be removed with potentially curative surgery.
“Our findings tell us that it is increasingly recognized that chemotherapy may be safely given to patients with intact tumors,” Dr. Chang said.
The researchers also found that despite the decrease in annual rates of primary tumor resection over the study period, the patients’ median 5-year relative survival rate improved during this time, from 8.6% in 1988 to 17.8% in 2009 (2010 survival data were not available). “
Although fewer people are getting primary tumors resected, a large proportion of patients with metastatic disease at diagnosis are still having them removed,” Dr. Chang said. “Together with the observation that primary tumor resection was more likely to be performed in younger patients who have colon rather than rectal cancers, this suggests that there may still be an overutilization of primary tumor resection and that careful consideration of the indication for such surgery should be made.” The study was published in the January issue of JAMA Surgery.
For more information, contact Dr. George J. Chang at 713-792-6940.
OncoLog, March 2015, Volume 60, Issue 3