Neoadjuvant CRT Tied to Survival Benefit in Older Rectal Cancer Patients

Neoadjuvant chemoradiation therapy (CRT) followed by surgical resection was associated with a survival benefit in elderly patients with locally advanced rectal cancer compared with other treatment sequences, according to a retrospective study.

After adjusting for confounders, use of neoadjuvant CRT was independently associated with a 25% decreased risk of death (adjusted HR 0.75, 95% CI 0.69-0.82) compared with surgery with or without adjuvant therapy, reported Melanie Goldfarb, MD, MSc, of Providence St. John’s Cancer Institute in Santa Monica, California, and colleagues.

Those who received neoadjuvant CRT were also more likely to undergo a R0 resection (adjusted OR 2.16, 95% CI 1.62-2.88), which independently improved overall survival (OS; P<0.001), they noted in JAMA Surgery.

Kaplan-Meier analyses with inverse probability of treatment weighting showed that 3-year and 5-year OS rates were:

• 68.9% and 51.1%, respectively, with neoadjuvant CRT followed by resection
• 64.4% and 43.0% with surgery plus adjuvant therapy
• 55.8% and 34.7% with surgery alone

Notably, less than 60% of patients older than 80 received neoadjuvant CRT, despite the fact that current guidelines recommend neoadjuvant CRT followed by resection for patients with locally advanced rectal cancer.

“There appears to be greater deviation from the standard of care by physicians when caring for older patients; this is not an isolated finding to locally advanced rectal cancer,” Goldfarb and colleagues noted. “It is our feeling that while the underutilization of NACRT [neoadjuvant CRT] is likely multifactorial, the biggest driver in this patient population is because of the age of the patient and the reluctance of physicians to treat patients with NACRT. And while that trend appears to be decreasing as we look at the utilization of NACRT over time, there are still many patients older than 80 years who do not receive the standard of care.”

“Clinicians should offer the standard of care to patients and not deviate from guidelines solely based on a patient’s chronological age,” they concluded. “Future clinical trials should aim to include older patients diagnosed with locally advanced rectal cancer to further validate these findings.”

In a commentary accompanying the study, José G. Guillem, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues noted that Goldfarb and colleagues based their conclusions on an analysis of groups that are “statistically different.”

“Although inverse probability of treatment weighting methodology was used to balance the groups, the authors do not provide any evidence that the groups were similar after inverse probability of treatment weighting adjustment,” Guillem and colleagues wrote. “A preferred approach may have been to select patients with similar baseline characteristics, group them by treatment received, and then compare outcomes.”

Furthermore, the use of binary logistic regression to compare neoadjuvant CRT versus surgery with or without adjuvant therapy, instead of the three individual treatments, was another concern, they added. “Therefore, we take issue with their usage of the words ‘independently associated’ because they do not actually compare the 3 treatment options independently; at best, there is an association.”

For this study, Goldfarb and colleagues included 3,868 patients ages 80 and older (mean age 83.4 years, 52.8% men) in the 2004-2016 National Cancer Database. These patients were grouped by treatment type into three cohorts — those who received surgery followed by adjuvant therapy (10.4%), those who received surgery alone (30.8%), and those who received neoadjuvant CRT followed by surgical resection (58.8%).

Factors independently associated with use of neoadjuvant CRT were more recent diagnosis, ages 80 to 85 years (vs 86 years and older), fewer comorbidities, larger tumors, and node-positive disease.

Goldfarb and team noted that when comparing patients who received both surgery and additional therapies, there was a significant survival advantage to neoadjuvant CRT over adjuvant therapy, with a median survival of 5.11 years with neoadjuvant CRT versus 4.19 years with adjuvant therapy.

The authors acknowledged that since their study period ended in 2016, the regimens used are not necessarily representative of the treatment strategies used today.