CHICAGO – Watchful waiting with careful surveillance may become an option for the majority of locally advanced rectal cancer patients who have a complete clinical response to neoadjuvant therapy, according to a review of 442 rectal cancer patients at Memorial Sloan Kettering Cancer Center in New York.
Seventy-three of those patients had a complete clinical response to neoadjuvant therapy and opted for watchful waiting instead of surgery after weighing the risks and benefits – including about a 25% chance of local recurrence – with their doctors.
Dr. J. Joshua Smith
At 4 years’ follow-up, 54 (74%) remained cancer free. Nineteen patients had local tumor recurrence, generally within 13 months. Two of those patients had successful local excisions, and the remaining 17 had salvage total mesorectal excisions (TME).
There were no statistically significant differences in 4-year disease-specific and overall survival among the 73 patients and 72 other patients who opted for TME after neoadjuvant chemotherapy and were found to have had pathologic complete responses.
“In our cohort, watch and wait was safe. It’s an effective treatment strategy achieving a high rate of rectal preservation in tumors that respond to neoadjuvant therapy. I don’t think the rectum needs to come out in everybody,” said investigator Dr. J. Joshua Smith, a surgical oncologist at Sloan Kettering.
Several studies have reported similar results similar to the Sloan Kettering study, but other investigations have been retrospective, so optimal patient selection, assessment of response, surveillance protocols, and other matters remain uncertain. Sloan Kettering and about 20 other cancer centers in United States – all members of the Rectal Cancer Consortium – recently launched a randomized clinical trial to get a better handle on those issues.
Locally advanced rectal cancer patients will be randomized to either chemoradiation for 5.5 weeks followed by folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CapeOX) over about 16 weeks, or FOLFOX/CapeOX first and chemoradiation second. Those who have a significant clinical response will then undergo watchful waiting; those who do not will have TME.
About 50 patients have enrolled in the phase II trial so far; the investigators are looking for more than 200.
“I think ‘prime time for watchful waiting’ is around the corner, but not yet here. It must be preceded by a prospective trial.” Meanwhile, “how we define complete clinical response is important” when considering watchful waiting, Dr. Smith said at the annual clinical congress of the American College of Surgeons..
At Sloan Kettering, where watchful waiting has become more popular in recent years, complete clinical response means no tumor or lymph nodes on imaging, and, on digital rectal exam (DRE) and proctoscopy, normal flat mucosa, smooth induration, no mass, no nodules, no ulcerations, and no luminal narrowing; a pale scar and telangiectasias are okay.
In the first year, surveillance includes DRE and endoscopy every 3 months and imaging every 6 months. In the second year, DRE and endoscopy come every 4 months, and imaging again every 6 months. From years 3 to 5, DRE and endoscopy are done every 6 months, and imaging every 6-12 months. After 5 years, surveillance is by yearly DRE and endoscopy.
When discussing the option with patients, they need to know – besides the risk of recurrence – that watchful waiting is currently not standard medical management; surveillance must be frequent; they are at risk for a more extensive salvage TME than they might have had otherwise; and the approach might compromise the chance of a cure, Dr. Smith said.
Dr. Smith said he has no relevant disclosures.