SAN FRANCISCO-Surgical resection may be unnecessary for rectal cancer patients with clinical complete response with chemo-radiotherapy, according to the results of a large observational study presented at the ASCO 2017 Gastrointestinal Cancers Symposium (Abstract 521).
Researchers with the International Watch and Wait Database Consortium (IWWD) found that 3-year survival rates for cancer-free patients after chemoradiation were comparable to those for surgical resection. Watchful waiting was evaluated in 679 patients with complete response to chemoradiation after induction therapy whose status was determined by physical exam, endoscopy, or imaging. Of these, 91 percent remained cancer-free at 3 years, similar to the historic survival rate with surgery.
Although other studies have found similar responses with a watch-and-wait approach, this is the largest series of rectal cancer patients who did not undergo surgery after chemotherapy and radiation therapy, Maxime van der Valk, MD, an IWWD researcher at Leiden University Medical Center in the Netherlands, told reporters during an online press briefing.
"Some people with rectal cancer undergo surgery after chemoradiation therapy, even though it may not be necessary," she said.
After a median follow-up of 2.6 years, 25 percent of patients underwent delayed surgery due to regrowth of the cancer, while 7 percent had distant metastases. The 3-year survival rate for all patients was 87 percent, and for those with local regrowth the rate was 87 percent, also consistent with historic rates for patients who undergo surgery.
Research shows as many as half of all rectal cancer patients will experience a clinical complete response, 10-20 percent will have a pathologic complete response, and local regrowth will occur in 15-25 percent.
More Data Needed
Rectal cancer treatment strategies vary widely across and within countries, but surgery is a standard part of care. In most countries, patients with stage II-IV rectal cancer receive chemotherapy and/or radiation before surgery.
Although in about 20-25 percent of patients the tumor completely disappears after pre-surgery therapy, it is not considered the standard of care to restage a tumor to see if surgery is still needed, according to van der Valk. Surgery is delayed in less than 5 percent of rectal cancer patients, it is estimated.
"What we know from the literature is that these results are similar to the survival rates of patients who had a complete response and then underwent standard surgery," said van der Valk.
The findings illustrate differences in induction therapy and imaging strategies for rectal cancer and provide some "crude" outcome data, according to the researchers.
"Further data collection on the watch-and-wait strategy for rectal cancer is needed to increase knowledge on oncological safety of omitting surgery.
"There are still major differences in watch-and-wait strategies worldwide, but it is important that restaging be performed in all patients who undergo chemo-radiotherapy to prevent unnecessary surgical procedures and to give patients the option for watch-and-wait," van der Valk explained.
"Despite seeing excellent outcomes in our study, we know the decision to undergo surgery is personal for every patient. When faced with the risk of permanent colostomy, some patients will prefer to avoid surgery, while others won't want to deal with the uncertainty of their cancer potentially recurring."
Surgery also carries the risk of sexual and urinary dysfunction, and possible surgical complications, and not all surgeons are comfortable with observation after chemo-radiotherapy, she noted.
Each Patient's Choice
Some of the results in this abstract are encouraging, said Steven R. Hunt, MD, Associate Professor, Section of Colon and Rectal Surgery at Washington University School of Medicine in St. Louis.
"The fact that 96 percent of patients who fail have an intramucosal recurrence should allow us to salvage the majority of patients who fail. Indeed, the registry shows that 87 percent of patients who fail this strategy were still alive at 3 years."
While watch-and-wait strategies are certainly likely to have a role in the future treatment of rectal cancers, the research describes a registry, "and in no way reflects current practices," he told Oncology Times.
"Based on the best available data on current neoadjuvant chemoradiation, the majority of rectal cancer patients will not have a complete response to chemoradiation, and will still require radical surgery," according to Hunt. "There is also compelling evidence that the addition of systemic chemotherapy to neoadjuvant chemoradiation will increase the number of patients who would be eligible for watch-and-wait treatment regimens."
There is a large NIH-sponsored trial underway using sequential chemoradiation followed by systemic chemotherapy with a goal of non-surgical treatment of complete clinical responders. "It should definitively allow us to assess the safety of this approach," he added.
Also, Hunt noted that the nature of a registry does not allow for a description of how these patients were identified and followed. "Ideally, based on the current NIH-sponsored trial, we will be able to establish clinical, endoscopic, and MRI predictors of success with this treatment strategy.
"The watch-and-wait approach to the treatment of rectal cancer is certainly going to be an enormous advance in therapy for this devastating disease. Our hope is that rectal cancer treatment begins to resemble the treatment of anal cancer-where surgery is only for salvage of failures of radiation and chemotherapy."
George J. Chang, MD, Chief of Colon and Rectal Surgery at MD Anderson Cancer Center, noted there continues to be growing evidence that surgery might not be necessary in patients who achieve a complete response to neoadjuvant therapy.
"Unfortunately there are still several limitations," he said.
It is not possible to know with certainty whether a patient with a clinical complete response has a pathologic complete response and even patients who have no tumor in the bowel wall can have residual lymph node disease.
"In addition, long-term data are still lacking, which is a particularly relevant issue since outcomes are truly excellent in patients with complete response who undergo resection whereas nearly a third of patients who undergo watch-and-wait will have tumor regrowth."
Chang said it is also unknown if results after salvage surgery after regrowth are as good as with surgery up front, nor is it known if delaying surgery until regrowth affects potential for sphincter preserving coloanal reconstruction when compared to primary surgery.
"The optimal follow-up regimen is unknown, but certainly requires closer follow-up than after radical resection," he added.
Kurt Samson is a contributing writer.