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Watch-and-wait strategy linked to shorter survival among some patients with rectal cancer
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A watch-and-wait strategy for certain patients with rectal cancer who achieved clinical complete response following neoadjuvant therapy yielded high rates of rectal preservation and pelvic tumor control, according to a recent study published in JAMA Oncology.
However, the approach appeared associated with shorter survival and higher incidence of distant progression among patients with local regrowth.
“Our group previously noted that a watch-and-wait approach was safe and efficacious after clinical complete response; however, the intervals of follow-up were short and the numbers of patients were small,” J. Joshua Smith, MD, PhD, a colorectal surgeon in New York who is affiliated with Memorial Sloan Kettering Cancer Center, and colleagues wrote. “To address these shortcomings, we aimed to evaluate long-term outcomes of 113 [patients with rectal cancer] managed by a watch-and-wait strategy after achieving a clinical complete response to neoadjuvant therapy to determine rates of rectal preservation salvage after local regrowth detection and pelvic tumor control. In addition, we sought to determine the relevant oncologic outcomes of survival and metastasis.”
In the retrospective case series, Smith and colleagues evaluated 249 patients who underwent neoadjuvant therapy for resectable, nonmetastatic rectal adenocarcinoma between Jan. 1, 2006, and Jan. 31, 2015.
The study population included 113 patients (median age, 67.2 years; range, 32.1-90) who had clinical complete response after therapy and agreed to a watch-and-wait strategy of active surveillance and potential salvage surgery. Another 136 patients (median age, 57.3 years; range, 25-87.9) underwent total mesorectal excision and had a pathologic complete response at resection.
The total mesorectal excision group served as a model representing optimal response to neoadjuvant therapy; the two approaches were not directly compared.
Patients who followed a watch-and-wait strategy were on average a decade older than those who achieved pathologic complete response. Those in the watch-and-wait group also had lower tumors (median height from anal verge, 5.5 cm vs. 7 cm) and were less likely to have received chemoradiation therapy only (27% vs. 61%).
Researchers used Kaplan-Meier estimates to analyze local regrowth and 5-year rates of OS, DFS and disease-specific survival.
Routine surveillance detected all 22 local regrowths in the watch-and-wait group, which were treated by salvage surgery (20 total mesorectal excisions and two transanal excisions). Almost all of these patients (91%) maintained pelvic control after salvage surgery. No recurrences occurred among patients who had achieved pathologic complete response.
In the watch-and-wait group, 93 of 113 patients (82%) attained rectal preservation; 91 of these patients had no local regrowths and two had local regrowths treated with transanal excision.
At median follow-up of 43 months (interquartile range, 27-43) from the end of neoadjuvant therapy, 19 (8%) of 249 patients analyzed died.
At 5 years, patients who underwent total mesorectal excision and had pathologic complete response achieved better outcomes than those in the watch-and-wait group (OS, 73% vs. 94%; DFS, 75% vs. 92%; and disease-specific survival, 90% vs. 98%).
In the watch-and-wait group, the rate of distant metastasis was higher among patients who had local regrowth than those who did not (36% vs. 1%; P < .001).
The study authors are leading a prospective, multi-institutional phase 2 study on the wait-and-watch approach.
“For now, unless the care team is truly multidisciplinary — and, thus, primed to evaluate, treat and diligently follow up patients in a close manner — the watch-and-wait approach may not be in the best interest of the patient,” Charles R. Thomas Jr., MD, professor of radiation medicine at Oregon Health & Sciences University, wrote in a related editorial. “In such cases, hold tight because it is likely that we will have stronger prospective data that may provide a sound foundation for evidence-based recommendations on how best to identify optimal candidates and guidelines for the execution of watch-and-wait care in resectable rectal cancer.” – by Jennifer Byrne
Disclosures: Smith reports travel support from Intuitive Surgical and an advisory role with Endogenesis Inc. Please see the study for all other researchers’ relevant financial disclosures. Thomas reports grants from NCI and serving as a co-principal investigator on the American College of Surgeons Oncology Group Z6041 trial, which examined a subset of patients with rectal cancer different from the subset investigated in the current study.
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