AT THE GASTROINTESTINAL CANCERS SYMPOSIUM
Patients with locally advanced rectal cancer who have a complete response to neoadjuvant therapy can skip surgery with little compromise in outcomes, according to a retrospective review that will be reported this week at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
Investigators at the Memorial Sloan-Kettering Cancer Center in New York studied 145 patients with stage I to III rectal cancer who received neoadjuvant therapy there between 2006 and 2013.
After a median follow-up of 3.5 years, there were no significant differences in disease-specific or overall survival between patients who had a clinical complete response to neoadjuvant therapy of radiation and chemotherapy and skipped surgery, and patients who underwent rectal resection (the current standard strategy in the United States) with a pathologic complete response. Additionally, more than three-fourths of the group skipping surgery had preservation of rectal function.
“Nonoperative management appears to be a safe and effective treatment strategy and achieves a high rate of rectal preservation,” senior investigator Dr. Philip B. Paty, a surgical oncologist at Memorial Sloan-Kettering Cancer Center, New York, commented in a press briefing held before the symposium.
Ideally, the findings would be tested in a randomized trial, he said; however, “there’s too many factors and too much patient autonomy involved here, so that no one really believes asking people to sign up for a randomized trial where rectal resection is decided by a flip of the coin would ever accrue patients.” Short of that, rigorous prospective studies, such as a phase II trial now open at the center, will provide critical information.
Press briefing moderator Dr. Smitha S. Krishnamurthi of Case Western Reserve University, Cleveland, commented, “These are important findings for patients with rectal cancer because removal of the rectum can result in altered bowel habits or the need for permanent colostomy. This study set the bar very high, comparing the results of nonoperative management to the results seen in patients who had no cancer left under the microscope at the time of surgery, and in this study, the nonoperative management appears to compare favorably.”
“We do need longer follow-up though, to be sure that these patients will have disease-specific survival that equals what is achieved with surgery in the long term,” she cautioned, such as the conventional 5 years of observation patients typically receive. “And then of course a prospective study also would be helpful to see the effects of this approach.”
In the study, Dr. Paty and colleagues identified 73 patients who had a clinical complete response (no cancer detected on physical exam, endoscopy, or imaging) to neoadjuvant therapy of radiation and chemotherapy and—by mutual agreement of physician and patient—had nonoperative management (watchful waiting), consisting initially of follow-up at 3- to 4-month intervals by digital rectal and endoscopic exams and at 6-month intervals by imaging. They used as a comparison group 72 patients who underwent standard total mesorectal excision and had a pathologic complete response (no viable cancer cells found microscopically in the resected tissue).
Results showed that 74% of the patients who did not have surgery had a sustained clinical complete response, with no regrowth of tumor during follow-up, reported Dr. Paty. Among the other 26% whose tumors regrew, most of the recurrences were clinically detectable and all patients had successful resections with clean margins. Overall, 77% of the nonsurgical patients had rectal preservation and 98% had local control.
The nonsurgical group did not differ significantly from the surgical group with respect to 4-year rates of disease-specific survival (91% vs. 96%) and overall survival (91% vs. 95%).
The investigators plan to report quality of life data in the future, Dr. Paty said. “But I think it’s pretty obvious to everyone who’s managed these patients that if you can avoid rectal surgery, the quality of life and particularly bowel function is far superior to those who have had rectal resection.”
Successful nonoperative management hinges critically on careful patient selection, close follow-up, and use of salvage surgery, he stressed. Additionally, “the informed consent process in nonoperative management is extremely important, and I always tell patients that they are taking a slight risk. It’s hard to imagine that not operating is going to have 100% equivalent cancer outcomes as operating. That is hard to believe. So we never sell it as being absolutely as good, but …with good follow-up, the results seem to be very close if not equivalent.”
In his experience, most patients are willing to accept this option. “In fact, I have only had two patients [out of more than 100] decline nonoperative management when I thought they were candidates—both young, both with young children, both not wanting to take even the slightest risk of leaving cancer in the rectal wall or their body,” he commented.
Adoption of nonoperative management has been slow in the United States for a variety of reasons, according to Dr. Paty. “I think the bottom line is that practicing watch and wait, nonoperative management is more difficult for the surgeon. It requires first the judgment that the cancer’s gone. You have to follow the patient longer after radiation; sometimes the complete response will take up to 3 months. And there is also the medical-legal issue of deviating from the standard of care. … So I think it was operationally a difficult thing to do, it didn’t fit with the existing paradigm very well.”
But that is changing as more data roll in. “What’s happened in the last I will say 2-3 years is that there are centers publishing their experience, ours being the largest outside Brazil and the first in North America. Another group in the Netherlands has published a group of about 25 patients,” he explained. “Talking with people at meetings around the world, centers are adopting it, and I think that many leaders in clinical trials in rectal cancer recognize that this option is not only reasonable, but perhaps it’s necessary to inform patients that it is an option.”
