Eight weeks post-radiation may be best time for rectal CA surgery

Last Updated: 2016-02-01

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Patients with rectal cancer treated with neoadjuvant chemoradiotherapy (nCRT) do best if their surgery is scheduled eight weeks after they complete radiation therapy, new research suggests.

"This confirms what we suspected, that the eight-week point is the appropriate time to operate," senior author Dr. Christopher R. Mantyh, of Duke University Medical Center in Durham, North Carolina, told Reuters Health by email.

"An inflection point of 56 days was found to have the highest likelihood of complete resection and pathologic downstaging. Prolonging the interval after chemoradiation failed to achieve additional benefit (downstaging) and resulted in worse long-term survival," he said.

"This provides guidance for surgeons who operate on patients with rectal cancer who have received neoadjuvant therapy and allows standardization of care for rectal cancer patients," he said.

Dr. Mantyh and colleagues searched the 2006-2012 National Cancer Data Base, which contains information on roughly 70% of newly diagnosed cancer cases in the U.S. and Puerto Rico from more than 1,500 cancer centers. They included the data from adults with stage II or III rectal adenocarcinoma who underwent nCRT followed by surgical resection. They excluded patients with more than one primary malignancy or missing timing data.

They considered time to surgery to be the difference between last date of preoperative radiotherapy and the date of surgery. The primary endpoints included resection margin positivity and pathologic downstaging.

To investigate the association between time to surgery and the study endpoints, and to establish an optimal time threshold for surgery, the authors used multivariable regression modeling with restricted cubic splines, and they reported their results online January 20 in the Journal of the American College of Surgeons.

Overall, the study involved 11,760 patients with a median time to surgery of 53 days (IQR 43-63 days).

After adjusting for demographic, clinical, tumor, and treatment characteristics, the highest likelihood of complete resection and pathologic downstaging occurred 56 days after the end of radiotherapy.

The adjusted risk of margin positivity was higher in patients who had surgery later than 56 days afterward (odds ratio 1.4, p<0.001), and the likelihood of downstaging increased up to 56 days after radiotherapy (56 or more days versus fewer than 56 days, OR 1.2, p=0.01).

Dr. Stephen M. Sentovich, a colorectal surgeon at the City of Hope National Medical Center in Duarte, California, told Reuters Health by email, "The most important implication of this study is that optimal timing of surgery needs to be looked at closely. It is important to determine optimal timing of surgery but I do not think that this study has completely answered that question due to the number of confounders/limitations to the study."

The study's confounders, he pointed out, which the authors acknowledged, included the population-based nature of the data, the inability to determine the specific chemotherapy regimen used and the reason for the interval between radiotherapy and surgery, and the inability to exclude short-course radiotherapy.

Also, said Dr. Sentovich, who was not involved in the study, "They did not control for surgery and pathology, which are major confounders."

"This study is a first step in defining some of the issues around optimal timing of rectal cancer surgery after chemoradiation, but we need better studies and I look forward to future studies to answer this question fully," Dr. Sentovich said.

The study was presented at the 127th Southern Surgical Association meeting in Hot Springs, Virginia, in December 2015.

SOURCE: http://bit.ly/1QTymQV

J Am Coll Surg 2016.