Factors predictive of neoadjuvant versus adjuvant chemoradiotherapy in locally advanced rectal cancer and the impact on overall survival

We investigated the effect of neoadjuvant versus adjuvant chemoradiotherapy on overall survival as well as the impact of demographic and clinical factors for the selection of each approach utilizing the National Cancer Data Base.

Adult patients with stage II and stage III adenocarcinoma of the rectum diagnosed from 2004 to 2013 were included. Chi-square analysis was used to compare demographic variables and clinical stage between the patients receiving neoadjuvant and adjuvant chemoradiotherapy. Univariate and multivariate logistic regression modeling was used to identify factors predictive of each treatment strategy. Kaplan-Meier and log-rank analysis and Cox proportional hazard modeling along with propensity score matching using variables known at the time of treatment sequence decision was performed to determine the effect on survival. A separate survival analysis was conducted including margin status to illustrate its effect on survival relative to adjuvant or neoadjuvant chemoradiation therapy.

A total of 20,114 patients were identified: 17,612 (87.6%) received neoadjuvant chemoradiotherapy. Factors associated with receipt of neoadjuvant chemoradiotherapy on multivariate analysis include the following: income greater than $46,000 (p < 0.01), treatment at an academic institution (p < 0.01), living greater than 50 miles from the treatment facility (p < 0.01), and year of diagnosis (p < 0.01). Compared to adjuvant chemoradiotherapy, neoadjuvant chemoradiotherapy was associated with a decreased risk of death on multivariate analysis (p = 0.05). When taking margin status into account, margin positivity in neoadjuvant chemoradiotherapy (NCRT) patients was shown to be a poor prognostic factor. Margin-negative NCRT patients had improved survival compared to margin negative adjuvant chemoradiotherapy (ACRT) patients.

The use of neoadjuvant chemoradiotherapy for locally advanced rectal cancer is possibly associated with an overall survival benefit compared to ACRT subject to the limitations of this analysis. Margin status affects survival greatly.