BARCELONA, Spain—The title of his presentation was “When Not to Operate in Rectal Cancer,” which the speaker admitted was an unusual topic for a surgeon to address.
But the focus was on organ preservation, and Geerard L. Beets, MD, of the Department of Surgical Oncology at the Netherlands Cancer Institute, speaking here at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer, explained why a watch-and-wait approach after neoadjuvant therapy is becoming more common.
Patient desire to avoid a colostomy is a factor, but perhaps most important: For non-metastatic rectal cancer after neoadjuvant therapy, overall survival appears to be the same for surgery and for watch-and-wait.
A study published in 2004 “shook the surgical world,” Beets said, as it showed an overall survival rate of 100 percent at five years for patients with stage 0 distal rectal cancer in an observation group following neoadjuvant therapy, compared with 88 percent in patients who had undergone resection (Ann Surg 2004;240:711-717).
Beets said four concepts are changing rectal surgery today:
- A balance is necessary between survival and function;
- Treatment can be adapted according to response to therapy;
- Surgery and radiotherapy are complementary; and
- Patience is of the essence: “Take your time before surgery for appropriate patients.”
“In the past 20 years we have obtained better survival and recurrence rates in rectal cancer by adding surgery and radiotherapy, but we may have forgotten a little bit about function, so now we are trying to get a balance—a better function without losing what we have gained in the last 20 years,” Beets said.
The concept of organ preservation does not follow technical developments as much as a change in the minds of surgeons and clinicians: “We are willing to let function be a part of the decision process.”
‘This is Something We Have to Get Used to’
Moving radiotherapy and chemotherapy upfront gives clinicians a lot of time to change a treatment plan, he said, “and this is something we have to get used to.”
In the past, the association between surgery and radiotherapy was not complementary, he explained. “The attitude was that we were targeting the same tumor so ‘why try to kill it twice, why irradiate the primary tumor and then take it out. But now we'd rather think of this as two complementary strategies—when radiotherapy is good, maybe we can omit the surgery; if surgery is very good maybe we can omit the radiotherapy, and in some patients, we need both.
“And we are learning there is no rush—if you see a good response take your time,” he said. “Deferral of surgery has been demonstrated in anal cancer, so why not do that in rectal cancer?”
Watch-and-Wait Was Better
Beets reviewed that groundbreaking study—a trial of 265 patients with distal rectal adenocarcinoma considered resectable. All the patients were treated with neoadjuvant Chemoradiation—fluorouracil and leucovorin, and 5,040 cGy of radiotherapy.
Patients with an incomplete clinical response were referred to have radical surgical resection; those whose surgery resulted in pathologic stage 0 were compared with patients who had a complete clinical response after non-operative treatment. Five-year overall survival was 100 percent in the non-operative observation group following neoadjuvant therapy versus 88 percent in the surgical patients.
Disease-free survival rates were also superior in the observation group—92 percent—versus 83 percent in the resection group.
A 10-year update published last year (Int J Rad Oncol 2014;88:822-828) showed that local recurrence developed in 31 percent of patients who had initial clinical complete response (when regrowths of 12 months or less were grouped with late recurrences). No metastases originated from regrowth.
More than half of those recurrences developed within 12 months, and salvage therapy was possible in at least 90 percent of the recurrences, leading to a local disease control rate of 94 percent and an organ preservation rate of 78 percent.
“The estimate of patients potentially ‘harmed’ by watch-and-wait was estimated at two to three percent, but that is the mortality of any major procedure,” Beets said.
Putting Data into Practice
Beets said his institution has changed its protocol since 2004 for locally advanced pancreas cancer following chemoradiotherapy.
“After 10 weeks if it looks like there is residual tumor, then we do a total mesorectal excision [TME],” he said. “But if there is a complete response, we wait; and if it is a near complete response, we do a local excision, or we wait even longer.”
Selection is usually by digital rectal exam and endoscopy.
“Most importantly, you share with the patient the uncertainty that everything is gone and that there are risks and benefits, and if the patient is willing to accept this, they can enter the protocol,” Beets said. “You tell the patient there is a risk for local regrowth and that we need to do rigorous follow-up.”
The follow-up includes MRI and endoscopy every three months for the first year and then every six months.
Beets said his institution is now following 121 patients treated for rectal cancer, 106 of whom opted for watch-and-wait and 15 who received total mesorectal excision. Their mean age was 63, two-thirds of patients were in stage III, and three-quarters had distal tumors.
The overall survival rate at 2.5 years for the watch-and-wait group is 97 percent, and 100 percent among the total mesorectal excision group. “The good survival is not because we did not operate; this is just a biological selection of favorable patients,” he said.
Beets listed what he and colleagues have learned during this 10-year period:
- They now wait 10 to 12 weeks for the reassessment after chemoradiotherapy;
- Primary assessment tools are digital rectal exam and endoscopy, and less of MRI;
- Assessment has become “a little more relaxed,” and near responders are accepted for watch-and-wait;
- “The test of time” is considered a diagnostic tool;
- There is less reliance on biopsies unless there is a clear regrowth;
- Transanal endoscopic microsurgery (TEM) could increase the number of organ preservations in smaller tumors, “but in big tumors with a residual lesion, I am not sure TEM will be very helpful”; and
- Clinicians are noticing a high interest by patients in organ preservation.
While organ preservation is feasible, it is not yet standard practice, Beets noted. “In intermediate/advanced tumors, where we have already decided to give upfront neoadjuvant therapy, you see a response rate of only 15 to 20 percent, but it is worth looking for a response.”
The largest group of patients who could benefit from organ preservation are those with smaller tumors. “About 50 percent of those tumors respond to adjuvant chemotherapy. With good selection and follow-up, the local regrowth rate is 10 to 15 percent, and salvage is possible with early detection of regrowth,” Beets said.
“My feeling is that there is little or no influence of watch-and-wait on survival, but that is a question mark until we have more evidence.”