For many patients with rectal cancer, the acquisition of a stoma is a terrible prospect.

To delay and potentially avoid this life-changing surgical intervention, the watchful waiting approach is increasingly being used in patients with locally advanced disease who have a complete response to neoadjuvant chemoradiotherapy.

Approximately 80% of these patients who experience a complete clinical response—a perfectly healed scar where the tumor was previously located and other favorable features—can forgo total mesorectal excision and preserve their rectum.

The success of the watch-and-wait approach in patients with complete response has prompted some centers to offer this approach also in patients who have a near-complete response to neoadjuvant chemoradiotherapy.

But the wait-and-see approach until patients have an almost complete clinical response is “very controversial,” said Dr. Alan Venook, a gastrointestinal oncologist at the University of California, San Francisco (UCSF). Medical news from Medscape.

“You don’t want to miss the chance to cure a patient,” Venook said.

A near complete clinical response essentially means that 8 weeks after total neoadjuvant therapy, there is no evidence of the tumor, but the tumor bed has not completely healed.

The goal of watch and wait in this scenario is to allow lesions that are in near-complete remission time to progress to complete remission.

However, there is no clear way to predict which tumors will develop complete clinical remission.

Recent studies evaluating conversion rates have found that between 39% and approximately 90% of patients with near-complete remission achieved complete remission. Some of the variation is likely due to differences in the clinical stage of the patients studied in each study and the limited number of patients achieving near-complete remission overall.

Further concerns are that waiting for near-complete responses to be fully developed allows additional time for metastasis in some tumors and that tumor regrowth is much higher compared to patients with complete responses.

A recent study found that 13% of patients who had a near-complete response to treatment and whose rectum was preserved in a watchful waiting phase developed distant metastases, compared to about 5% of patients who had a long-term complete response to treatment. The study also found that just over half of patients who had a near-complete response to treatment experienced tumor regrowth, compared to about one in five patients who had a complete response to treatment.

But even if the tumor grows again, “surgery is still curative,” explains Dr. Julio Garcia-Aguilar, a pioneer of the expectant treatment of rectal cancer.

And overall, about 50–60% of patients with near complete remission can avoid surgery and preserve their rectum.

Selection of patients for the waiting phase

To decide which patients are appropriate for the wait-and-see approach, it is crucial to understand how a near-complete clinical response was defined in the OPRA trial. This groundbreaking randomized trial led by Garcia-Aguilar established the wait-and-see approach as a treatment option for rectal cancer.

OPRA defined near complete remission as no visible tumor but mild erythema in the tumor bed, superficial ulceration, minor mucosal changes or small nodules, and irregular mucosa. Criteria also included no palpable tumor with smooth induration or minor mucosal changes on digital rectal examination.

The National Comprehensive Cancer Network followed this definition when it first recommended “watch-and-wait” as an option for near-complete remission in its 2023 rectal cancer guidelines. The group also added some MRI requirements.

UCSF offers some patients with near-complete remission the option of wait-and-see therapy, but the decision is made by a tumor board on a case-by-case basis, taking into account numerous indicators of tumor aggressiveness.

And even then, “in many cases we had difficulty figuring out which decisions were the right ones,” Venook said.

As for the patients selected for watchful waiting, Venook pointed out that UCSF has top-notch surgeons, radiation oncologists, medical oncologists and pathologists who have the resources to closely monitor patients.

For group practices that do not have the resources of a large cancer center, waiting and observing until rectal cancer treatment is in near-complete remission is “really a big challenge,” Venook said.

Garcia-Aguilar, a colorectal surgeon at Memorial Sloan Kettering Cancer Center in New York City, said that after years of studying the issue, he agrees with a watchful waiting period for patients in near-complete remission, as long as it is done carefully and patients comply with ongoing monitoring.

Garcia-Aguilar explained that after diagnosing a near-complete remission at 8 weeks, the patient must return 6 weeks later after total neoadjuvant therapy. At that point, it is time to assess whether or not this near-complete remission will evolve into a complete remission.

If complete remission develops, monitoring continues about every 8 weeks, but if the tumor stops responding, “you take the patient to the operating room,” Garcia-Aguilar said.

As for the larger safety concern—that tumors that are in near-complete remission will metastasize—Garcia-Aguilar believes micrometastases are likely already present when rectal cancer is first diagnosed and will manifest “no matter what happens to the primary tumor.”

For this reason, he noted, “I don’t think the risk is very high” if surgery is postponed for a few months to give patients in near-complete remission a chance to keep their rectum.

The question of metastases can be answered with a randomized study in which surgery is compared with a watchful waiting approach in patients with rectal cancer with almost complete remission.

Garcia-Aguilar, however, does not believe that trial will happen. Patients would not choose surgery once they learn that it may help them avoid a permanent stoma, he says.

Venook did not provide any information. Garcia-Aguilar reported personal fees from Medtronic, Johnson & Johnson and Intuitive Surgical.

M. Alexander Otto is a physician assistant with a master’s degree in medical sciences and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news organizations before joining Medscape Medical News. Email: [email protected].