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Watch-and-wait may be option for some rectal cancer patients after chemoradiation

By Joan Stephenson

NEW YORK (Reuters Health) - Among patients with locally advanced rectal cancer who have a clinical complete response to neoadjuvant chemoradiation, most will not experience tumor regrowth and may avoid radical surgery when a wait-and-watch approach is used, new research suggests.

The findings, from a systematic review and meta-analysis of nearly two dozen studies, also show that nearly all of those who experienced tumor regrowth remained candidates for salvage therapy.

“The implication of this is that there is a subset of patients who may be able to avoid the morbidity of rectal cancer surgery, including living with a permanent colostomy,” Drs. Nancy Baxter and Fahima Dossa, of the University of Toronto, Canada, told Reuters Health in a joint email.

“However, patients in these studies were treated in centers with an interest in a watch-and-wait approach and were followed very closely,” they cautioned.

Many patients are eager to avoid surgery to explore a watch-and-wait strategy with their surgeons, but clinicians have been concerned that allowing the tumor to regrow may result in resectable disease becoming unresectable, Drs. Baxter and Dossa noted.

To examine the safety of a watch-and-wait approach by quantifying the rates of tumor regrowth and noting management options at the time of regrowth, the researchers identified 23 studies (with median follow-ups of 12 months to 68 months) that met inclusion criteria.

The studies involved 867 patients (ages 39 to 86; 62% male) with rectal adenocarcinoma managed by watch-and-wait after clinical complete response (absence of clinical, endoscopic, or radiologic evidence of disease) to neoadjuvant chemoradiation.

In three of the studies, outcomes for watch-and-wait patients were directly compared with those of patients who had radical surgery after a complete clinical response. In five studies, outcomes were directly compared with those of patients who had a pathologic complete response (which can be determined only after surgical resection).

The primary outcome was proportion of watch-and-wait patients who had local regrowth (clinical, endoscopic, or radiological evidence of intraluminal tumor). Other outcomes assessed included non-regrowth recurrence (development of non-luminal intrapelvic or distant metastatic disease), cancer-specific mortality, and overall survival.

The pooled proportion of watch-and-wait patients with local regrowth within two years was 15.7%, the researchers report in The Lancet Gastroenterology and Hepatology, online May 4. Of 157 patients with data available, three (1.9%) were unable to have salvage therapy because of the extent of disease progression.

Non-regrowth recurrence was not significantly different for watch-and-wait patients compared with both patients who had a pathological complete response identified at resection (hazard ratio, 1.46; 95% confidence interval, 0.70-3.05), or with patients who had a clinical complete response and were also treated with surgery (HR, 0.58; 95% CI 0.18-1.90).

Disease-free survival was significantly better among patients who had a pathological complete response after surgery compared with patients treated with watch-and-wait. However, there was no significant difference between groups for cancer-specific mortality or overall survival.

Although larger studies are needed for definitive conclusions about safety, the analysis of existing evidence suggests that the watch-and-wait strategy is associated with a fairly low risk of regrowth and excellent survival independent of whether patients undergo surgery, and it does not preclude future surgery if regrowth occurs, Drs. Baxter and Dossa said.

They also stressed that watch-and-wait should only be considered for highly selected patients who have the appropriate tumor response and who are highly motivated to be part of a close follow-up regimen.

The authors report that two of 1,000 patients treated with watch-and-wait will not be able to receive salvage therapy at the time of recurrent disease, but “this risk might be considered acceptable in many cases,” given the 10-times higher risk of perioperative mortality of rectal cancer surgery, note Drs. Maxime J. M. van der Valk of Leiden University Medical Center, the Netherlands, and colleagues in an accompanying editorial.

For carefully selected patients, the watch-and-wait strategy “may be a viable alternative to radical surgery with its significant drawbacks,” Dr. Christopher Willett, chair of the department of radiation oncology at Duke University School of Medicine in Durham, North Carolina, told Reuters Health by email.

However, experience directly comparing watch-and-wait to radical surgery in patients with clinical complete response is “very limited,” cautioned Dr. Willett, who was not involved in the study.

“Results from ongoing prospective trials and a pooled international data base will be critical in the assessment of the long-term oncologic safety of this organ-preserving approach, as well as (in) providing guidance in the clinical decision making in the care of these patients,” he said.

To provide evidence on the risk and benefits of watch-and-wait strategies, the International Watch and Wait Database (http://www.iwwd.org/) was established in 2014 to collect all available retrospective and prospective data on the approach.

The authors reported no competing interests.

SOURCE: http://bit.ly/2rdKEO3 and http://bit.ly/2pIGfTv

Lancet Gastroenterol Hepatol 2017.