Tumor Response and Its Impact on Treatment Failure in Rectal Cancer: Does Intensity of Neoadjuvant Treatment Matter?

Simple Summary: The response to neoadjuvant treatment in rectal cancer varies among patients, while the evidence of benefit from additional adjuvant chemotherapy, especially in patients with persistent tumor and/or lymph node metastases, is unclear. In our cohort study of 1778 patients, we showed that persistent tumor and/or lymph node metastasis after intensified neoadjuvant treatment, e.g., total neoadjuvant treatment (TNT), was not more strongly associated with an extensive risk of treatment failure (TF, local recurrence and/or distant metastasis) than after less intensive neoadjuvant treatment, e.g., 5-flurouracil-based chemoradiotherapy (5-FU CRT). These results may help clinicians to individualize their surveillance strategies, but do not provide an argument for adding additional chemotherapy in non-responders after TNT. Objectives: Additional adjuvant treatment in patients with rectal cancer with limited response to neoadjuvant treatment to mitigate their higher risk of treatment failure remains controversial. Methods: This is a post hoc analysis of a cohort study of 3 randomized phase 2 or 3 trials (CAO/ARO/AIO-94, -04, and -12 trial) that included 1948 patients with locally advanced rectal adenocarcinoma. After excluding patients with missing information, 1788 patients (1254 men and 524 women; median age: 62.6 years, age range: 19–84 years) were eligible. We analyzed the extent of tumor response and its association with the incidence of treatment failure after different neoadjuvant treatment approaches. Results: Tumor response was significantly enhanced with more intensive neoadjuvant treatment. After a median follow-up of 55 months for the entire cohort (IQR: 37 months–62 months), the incidence of treatment failure (TF) stratified by tumor response or post-neoadjuvant pathological outcome was not significantly affected by the intensity of neoadjuvant treatment, whereas the ypTNM stage was significantly associated with the risk of treatment failure. Conclusions: In this cohort study, we provide evidence that limited or no response to intensified neoadjuvant treatment protocols is not likely to be more strongly associated with an extensive risk of TF after 5-FU CRT+/− adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]