Researchers define optimal time to rectal cancer surgery following chemoradiotherapy

Optimal completeness of resection and tumor downstaging appear to occur when patients with rectal cancer undergo surgery 8 weeks following neoadjuvant chemoradiotherapy, according to the results of a retrospective study.

Data have shown neoadjuvant chemoradiotherapy leads to tumor regression and improved long-term local control for patients with locally advanced rectal cancer, according to study background. However, questions remain as to the optimal interval between chemotherapy and surgery.

“In the global picture, there is a lot of discussion about whether waiting longer for surgery is better, but none of this is backed up by good modeling data,” Christopher R. Mantyh, MD, FACS, a colorectal surgeon at Duke University School of Medicine, said in a press release. “This kind of analysis is what we need in medicine and surgery.”

Mantyh and colleagues used the National Cancer Data Base to identify 11,760 patients (median age, 58 years) who underwent neoadjuvant chemoradiotherapy and surgical resection for rectal cancer between 2006 and 2012. The cohort included patients with stage II (n = 3,980) and stage III (n = 5,014) disease.

Margin positivity and pathologic downstaging served as the primary endpoints. Key secondary endpoints included unplanned postoperative readmission within 30 days of hospital discharge, 30-day mortality and OS.

Researchers defined time to surgery as the interval between the patient’s last date of radiotherapy and date of surgery. The median time to surgery after preoperative radiotherapy was 53 days (interquartile range, 43-63).

The researchers observed that an interval of exactly 8 weeks (56 days) appeared to confer the greatest benefit regarding complete resection and pathologic downstaging.

Mantyh and colleagues stratified their cohort into short-interval (58.5%; < 56 days) and long-interval (41.5%; 56 days) groups.

Patients receiving surgery after an interval greater than 56 days tended to be older (P < .001), black (P = .003), treated at an academic center (P < .001) and less likely to have private insurance (P < .001).

Patients in the long-interval group had a high likelihood of downstaging (OR = 1.4; 95% CI, 1.21-1.61) and higher odds of positive margins (OR = 1.12; 95% CI, 1.02-1.23). These data led researchers to conclude that “56 days is the optimal balance between the benefit of downstaging and the risk of local tumor growth.”

Patients in the long-interval group had a lower risk for 30-day hospital readmission (OR = 0.68; 95% CI, 0.58-0.81) and comparable risk for 30-day mortality (OR = 1.09; 95% CI, 0.59-1.99). However, they also experienced worsened long-term OS outcomes (adjusted HR = 1.2; 95% CI, 1.1-1.32).

The researchers acknowledged limitations of their study, including their inability to ascertain the reasons contributing to the intervals between radiotherapy and surgery.

“While we assume that most intervals were due to patient scheduling or other nonmedical reasons, there may be a proportion of patients that experienced toxicity during their preoperative treatment and thus required additional recovery time,” the researchers wrote.

Further, the researchers did not have access to data regarding exact chemotherapeutic regimens used.

“Our study objectively determined 56 days (8 weeks) as the optimal time for surgery after completion of radiation therapy as part of neoadjuvant chemoradiotherapy,” Mantyh and colleagues wrote. “Our study advocates for incorporating coordinated care quality metric into existing best-practice recommendations for rectal cancer.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.