Watch and Wait in Rectal Cancer: Worse Survival for Some

Roxanne Nelson, RN, BSN

January 10, 2019

Experts have been debating whether rectal cancer patients who respond optimally to chemoradiation need to undergo surgery as well, or whether they can be followed with a watch-and-wait strategy.  

Skipping surgery has the obvious advantage of preserving rectal sphincter function, but new findings show that at least for some patients, this can be associated with worse survival.

Researchers from Memorial Sloan Kettering Cancer Center (MSKCC) found that rectal cancer patients who opted for "watch and wait" had poorer survival and a higher incidence of distant progression when compared with similar patients who underwent total mesorectal excision and achieved a pathologic complete response (pCR),

At 5 years, overall survival was 73% in the watch and wait groups vs 94% in the surgical group. Similarly, disease-free survival was 75% vs 92%, respectively, and disease-specific survival was 90% vs 98%.

The new findings were published online today in JAMA Oncology.

In an accompanying editorial, Charles R. Thomas Jr, MD, of the Department of Radiation Medicine, Oregon Health and Science University, Portland, ponders if watch and wait in rectal cancer is ready for "prime time."

He noted that the multidisciplinary cancer team at MSKCC carefully monitored a watch-and-wait strategy in a group of patients and then compared outcomes to those who had a pCR following sequential preoperative therapy and total mesorectal excision. "This is an important comparison because advocates of a wait and watch approach are hoping that a clinical complete response is a reliable surrogate for a pCR," he writes.

By comparing 5-year outcomes between groups, these data can help a cancer care team and patients in the decision-making process. Thomas notes, "despite earlier reports from the well-designed International Watch and Wait database that most local recurrences occur within 24 months, the results of the present study with a slightly longer median follow-up period of 3.6 years suggest that local recurrence may not plateau quite so soon."

In addition, even though salvage therapy in this cohort appears to be effective and intrapelvic bowel disease well controlled, some patients did experience distant recurrence.

So what is the takeaway?

Thomas emphasizes that unless the care team is truly multidisciplinary and "primed to evaluate, treat, and diligently follow-up patients in a close manner," the wait and watch strategy may not be in the patient’s best interest.

However, he notes that there are other trials ongoing and suggests that clinicians "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 execution of watch-and-wait care in resectable rectal cancer."

Worse Long-Term Outcomes

Sphincter preservation for patients with invasive adenocarcinoma of localized rectal cancer has been a topic of great interest, with strong viewpoints on both sides of the coin.

Previous research has suggested that there may be patients who do not require the standard radical surgery, and thus can avoid a permanent colostomy. The team at MSKCC had previously found the wait-and-watch approach to be safe and efficacious after achieving a complete CR, but the follow-up intervals were short and the sample size small.

This latest study, led by J. Joshua Smith, MD, PhD, of the Colorectal Service, Department of Surgery at MSKCC, was a retrospective case series analysis to evaluate the long-term outcomes of 113 rectal cancer patients who were managed by a watch-and-wait approach after achieving a complete CR following neoadjuvant therapy.

They were compared with a cohort of 136 patients who underwent total mesorectal excision and achieved a pCR after resection. The median follow-up was 43 months.

In the watch and wait cohort, 22 patients (20%) developed local regrowth, which corresponded to a 5-year actuarial rate of 21%, and the 5-year rate of rectal preservation was 79%. Clinical T2/T3 stage, clinical nodal stage, neoadjuvant regimen, tumor size, age, and height of tumor from the anal verge were not significantly associated with local regrowth in a univariate analysis (P > .05 for all).

The median time to local regrowth for this subset was 11.2 months and the majority of patients had a local regrowth in the first 12 months.  All 22 patients underwent salvage surgery, and eight subsequently developed distant metastases.

Overall, 91 patients (81%) in the wait and watch cohort remained free of disease in the rectum following neoadjuvant therapy, and 93 patients (82%) had rectal preservation. At the end of the follow up period, 11 patients (10%) had a permanent stoma vs 21 patients (15%) in the pCR group.

At a median follow-up of 43 months, 19 patients (8%) in the entire cohort had died. A total of 9 patients (8%) in the watch and wait group developed distant metastases compared with 5 patients (4%) in the pCR group.

Smith and colleagues conclude that while their data suggest that watch and wait may be effective in most patients, "better risk stratification is needed to inform more precise patient selection and to better understand which patients should be excluded from a wait and watch strategy to minimize local failure and distant progression."

The study was supported by a number of research grants, including those from the National Cancer Institute, the American Society of Colon and Rectal Surgeons, and the American Association of Cancer Research. Several of the coauthors report relationships with industry as noted in the paper. Thomas reports receiving grants from the National Cancer Institute and serving as a coprincipal 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 present study.

JAMA Oncol. Published online January 10, 2019. Abstract, Editorial    

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