A watch-and-wait strategy for patients with rectal cancer who achieve clinical complete response after neoadjuvant therapy may not be ready for prime time, according to a retrospective case series from Memorial Sloan Kettering Cancer Center (MSKCC).
While watch-and-wait resulted in high rates of rectal preservation and pelvic tumor control, overall survival at 5 years was 73% for patients who opted for this strategy compared with 92% for those who underwent total mesorectal excision and had pathological complete response (pCR), reported J. Joshua Smith, MD, PhD, of MSKCC in New York City, and colleagues.
Patients in the watch-and-wait group were older by roughly a decade, but disease-specific survival at 5 years was also lower in this group (90% vs 98%), they wrote in JAMA Oncology.
Overall, distant metastases were diagnosed in 8% of patients in the watch-and-wait group and 4% of patients in the pCR group. In patients who chose watch-and-wait, those who had local regrowth were significantly more likely to also have distant metastases compared with those with no local regrowth (36% vs 1%, P<0.001).
Based on these data, a watch-and-wait strategy may be effective in most patients, but “better risk stratification is needed to inform more precise patient selection and to better understand which patients should be excluded from a watch-and-wait strategy to minimize local failure and distant progression,” the authors wrote.
In an Editor’s Note that accompanied the study, Charles R. Thomas Jr., MD, of Oregon Health and Science University in Portland, agreed and added that “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.”
The rate of distant metastases is particularly important, Scott R. Steele, MD, of the Cleveland Clinic in Ohio, told MedPage Today, because the major issue that still remains is how to identify patients that will have no recurrence after a clinical complete response.
“Further innovations are needed to help identify this cohort, perhaps on a molecular or tumor biology level to come closer to matching [clinical complete response] with pCR,” said Steele, who was not involved in the study.
Additionally, although the majority of patients with local regrowth experienced it in the first 12 months, data from the study indicated that recurrence could occur at time periods further out from those previously identified, “highlighting the importance of continued surveillance of patients that undergo this treatment regimen,” he noted.
Steele said that data from a MSKCC-led, prospective, multi-institutional phase II trial that will help define anal cancer management strategy in these patients is anticipated (Cleveland Clinic is also participating). The study is investigating the use of total neoadjuvant therapy and selective non-operative management in patients with locally advanced rectal cancer.
For the current study, the researchers included data from patients diagnosed with rectal adenocarcinoma from 2006 to 2015 at MSKCC. Included participants had a clinical complete response after neoadjuvant therapy and agreed to a watch-and-wait strategy (113 patients) or underwent total mesorectal excision and had pCR (136 patients).
Patients who chose the watch-and-wait strategy were significantly older than those who underwent surgery (67.2 vs 57.3, P<0.001) and had cancers closer to the anal verge (median height from anal verge 5.5 vs 7.0 cm). Treatment with chemoradiation only was more common in patients in the pCR group (61% vs 27%).
Local regrowth occurred in 22 of 113 patients in the watch-and-wait group, with a median time to regrowth of 11.2 months. Salvage surgery resulted in pelvic control in 20 of 22 (91%). Overall, rectal preservation was achieved in 82% of patients in the watch-and-wait group. In comparison, no pelvic recurrences occurred in the pCR group.
Smith and colleagues reported ties to various industry.
Thomas reported receiving grants from the National Cancer Institute and serving as co-principal investigator with one of the study authors on the American College of Surgeons Oncology Group Z6041 trial.