Patients who are able to undergo watchful waiting instead of immediate surgery for locally advanced rectal cancer can see lasting gains in quality of life (QOL), according to a new analysis of two clinical trials.

Researchers found that of nearly 400 patients who received total neoadjuvant therapy, those who had a complete response and could undergo watchful waiting showed improved QOL over 5 years. Compared with patients who had immediate surgery, they had fewer bowel symptoms and better social and physical functioning.

A key caveat, according to the researchers, is that relatively few study patients — about 1 in 8 — underwent watch-and-wait. And about half of them eventually needed salvage surgeries due to recurrence. 

Still, the analysis confirms what patients and clinicians have long suspected, said Daniel Chu, MD, a professor and director of gastrointestinal surgery at the University of Alabama at Birmingham. 

When rectal excision can be avoided, “people generally have much better function and much better quality-of-life measures across the board,” Chu told Medscape Medical News.

And with rectal cancer accounting for a large share of the rise in colorectal cancer among younger adults, giving patients the option to preserve the organ is increasingly important.

“That’s why I think total neoadjuvant therapy is so powerful in this changed environment,” Chu said.

He co-authored a commentary published with the findings in JAMA Network Open. 

On the basis of prior research, patients who undergo watch-and-wait after having a complete response to total neoadjuvant therapy have about a 50-50 chance of avoiding total mesorectal excision over the next 5 years. 

Little is known, however, about QOL with the approach.

To investigate, researchers led by Markus Diefenhardt, MD, of the University of Frankfurt, used data from two phase 2 trials conducted at centers throughout Germany. Together, they involved 385 patients (median age, 60 years) diagnosed with cT3 to cT4 or node-positive rectal adenocarcinomas.

In one trial, all patients received chemoradiotherapy (CRT) with either induction or consolidation chemotherapy and then were scheduled for total mesorectal excision. In the other trial, patients who had a complete clinical response to neoadjuvant CRT plus chemotherapy were scheduled for watch-and-wait, while the rest had surgery.

In all, 56 of 385 patients underwent watch-and-wait. Most trial participants (346) completed two standard QOL questionnaires, with 185 completing them throughout 5 years of follow-up. 

Overall, the analysis found, patients in the watch-and-wait group experienced significantly fewer bowel issues vs the immediate-surgery group. Their average scores for fecal incontinence and stool frequency were about 20 points lower, while their scores related to flatulence and buttock pain were 15 and 12 points lower, respectively.

According to the researchers, a difference of 10-20 points in those measures is a moderate clinically meaningful difference, while anything greater than 20 points signifies a “large” difference.

The watch-and-wait group also scored better in QOL measures around embarrassment (17 points), social and physical functioning (10 points in both cases), and their ability to perform daily tasks (14 points). 

For several measures, the advantages were even greater for the 29 patients under watchful waiting who had a sustained clinical complete response for at least 3 years. But, the researchers pointed out, meaningful differences existed even when patients with disease progression and salvage surgery were included.

The study has limitations beyond the small number of patients in the watch-and-wait group, both Chu and the authors stressed. Selection bias is an issue, as patients who were doing well may have been more likely to adhere to QOL reporting over time. Chu also noted that women accounted for only one third of patients.

In the real world, the watch-and-wait approach has its own challenges for patients, including regular clinical visits, endoscopy, and MRI/CT imaging. The intensity “might relax” after 2 years, Chu said, but close follow-up remains necessary for 5 years.

In this study, almost half of patients who began watch-and-wait (27 of 56) ended up needing salvage surgery, with nine (16%) developing distant metastases. Among patients who had immediate rectal excision, 5% and 21% developed a local or distant recurrence, respectively.

But while recurrence is common, Chu and his co-editorialist wrote, increasing evidence shows that with intensive surveillance, overall survival is similar for patients who ultimately need salvage surgery and those who have surgery immediately.

The “very large difference” in QOL seen in this study, Chu said, further supports efforts to spare select patients rectal excision, when appropriate.

The original trials were funded by German Cancer Aid and Medical Faculty of Tübingen. Chu had no relevant disclosures.