Having an ostomy is a dreaded prospect for many patients with rectal cancer.
To defer, and potentially avoid, this life-altering surgery,
About 80% of these patients who have a complete clinical response — a perfectly healed scar where the tumor used to be and other favorable features — can forgo total mesorectal excision and preserve their rectum.
The success of watch-and-wait among complete responders has led some centers to offer the approach in patients with near-complete responses to neoadjuvant chemoradiation.
But watch-and-wait for near-complete clinical responders “is very controversial,” Alan P. Venook, MD, a gastrointestinal oncologist at the University of California, San Francisco (UCSF), told this news organization.
“You sure as hell don’t want to miss a chance to cure a patient,” Dr. Venook said.
A near-complete clinical response essentially means there is no sign of the tumor 8 weeks after total neoadjuvant therapy, but the tumor bed hasn’t completely healed.
The goal of watch-and-wait in this scenario is to give near-complete response lesions time to become complete responses.
But there’s no clear way to predict which tumors will evolve into a clinical complete response.
Recent studies evaluating the conversion rate have reported that anywhere from 39% to about 90% of near-complete responders became complete responders. Some of the variation likely comes down to differences in the clinical stage of patients evaluated in each study as well as the limited number of patients who achieve a near-complete response overall.
Other concerns have emerged that waiting for near-complete responses to become complete leaves extra time for some tumors to metastasize and that tumor regrowth is much higher compared with complete responders.
A recent study found that 13% of near-complete responders who preserved their rectum on watch-and-wait developed distant metastases vs about 5% of long-term complete responders. The study also found that just over half of near-complete responders have tumor regrowth compared with about one in five complete responders.
But even with regrowth, “surgery is still curative,” explained Julio Garcia-Aguilar, MD, PhD, a pioneer of watch-and-wait for rectal cancer.
And overall, around 50%-60% of patients with a near-complete response can avoid surgery and preserve their rectum.
Selecting Patients for Watch-and-Wait
The key to deciding which patients are right for watch-and-wait is to understand how a near-complete clinical response was defined in the OPRA trial, a landmark randomized trial led by Dr. Garcia-Aguilar that helped establish watch-and-wait as an option in rectal cancer.
OPRA defined a near-complete response as no visible tumor but, in the tumor bed, mild erythema, superficial ulceration, minor mucosal abnormality or small nodules, and an irregular mucosa. The criteria also included no palpable tumor with smooth induration or a minor mucosal abnormality on the digital rectal exam.
The National Comprehensive Cancer Network mirrored the definition when, for the first time, it recommended watch-and-wait as an option for near-complete response in its 2023 rectal cancer guidelines. The group also added a few MRI requirements.
UCSF offers the watch-and-wait option to some patients with near-complete responses, but each decision is made on a case-by-case basis by a tumor board considering numerous measures of tumor aggressiveness.
Even then, “we have, in many cases, struggled to figure out what the right choices are,” Dr. Venook said.
For those chosen for watch-and-wait, Dr. Venook noted that UCSF has top-notch surgeons, radiation oncologists, medical oncologists, and pathologists who have the resources to follow patients closely.
For community practices without the resources of a major cancer center, watch-and-wait for near-complete response to rectal cancer “is really asking a lot,” Dr. Venook said.
Dr. Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, explained that after years of studying the issue, he is comfortable with watch-and-wait in near-complete responders as long as it’s done carefully and in patients who will comply with ongoing surveillance.
Dr. Garcia-Aguilar explained that, after diagnosing a near-complete response 8 weeks following total neoadjuvant therapy, the patient needs to come back 6 weeks later. At that point, it’s time to assess whether that near-complete response is evolving into a complete response or not evolving into a complete response.
If it’s evolving into a complete response, surveillance continues about every 8 weeks, but if the tumor has stopped responding, “you take [the patient] to the operating room,” Dr. Garcia-Aguilar said.
As for the bigger safety concern — that near clinical complete response tumors will metastasize — Dr. Garcia-Aguilar’s opinion is that micrometastases are probably already there when the rectal cancer is first diagnosed and will manifest themselves “no matter what happens to the primary tumor.”
Because of that, he noted, “I don’t think the risk is very high” when surgery is delayed a few months to give near-complete response patients a chance to keep their rectum.
The way to answer the metastasis question is to do a randomized trial pitting surgery against watch-and-wait in patients with near-clinical complete response rectal cancer.
However, Dr. Garcia-Aguilar doesn’t think that trial will ever happen. Patients won’t allow themselves to be randomized to surgery once they find out they might be able to avoid a permanent ostomy, he said.
Dr. Venook had no disclosures. Dr. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson, and Intuitive Surgical.
A version of this article first appeared on Medscape.com.
