Discussion
mrT4 disease, T4 disease, rectal cancer
REGRESSION, COLORECTAL CANCER, DISEASE, PRIMARY TUMOR, METASTASES, RECTAL CANCER
Complete primary tumor regression has become a relevant endpoint in rectal cancer management. Achievement of a complete clinical response to neoadjuvant treatment strategies has provided the opportunity to avoid major abdominal surgery, its associated morbidity and the requirement for temporary or definitive stomas. Long-term data suggests that nearly 70% of patients who achieve a cCR will never require radical surgery [In this setting, changes in neoadjuvant treatment regimens may now be driven by the attempt to increase response rates. Most studies at this point, presented nearly 25% cCR rates among centers practicing WW and using standard CRT regimens similar to the experimental arm of the German trial (2 cycles of 5FU-based chemotherapy) [A single phase 2 study performed using additional cycles of bolus 5FU aimed at improving cCR (instead of pCR) rates [Another prospective non-randomized study also suggested the potential effects of consolidation chemotherapy to response in rectal cancer. The “timing” trial included patients with locally advanced disease into 4 different arms (sequentially, not randomized) [Finally, with the introduction of the TNT concept – providing adjuvant chemotherapy immediately before nCRT (induction) or after nCRT (consolidation), initial experiences (using FOLFOX as consolidation) suggested an increase in complete response and in the chances of organ preservation among these patients [In summary, there is evidence to support that consolidation chemotherapy may contribute to improve response rates in rectal cancer following nCRT. Both 5FU-only and 5FU/Oxaliplatin-based chemotherapy consolidation regimens have shown promising results [For these reasons, we decided to design a study to address the impact of 2 different consolidation chemotherapy regimens in complete primary tumor response to treatment in rectal cancer [The decision to exclude patients with mrT4 disease was due to the fact that these patients (T4 disease irrespective of N stage) are at high-risk for development of subsequent metastases. Currently, guidelines recommend the use of combined chemotherapy regimens (5FU and oxaliplatin-based) in the adjuvant setting for such patients with colorectal cancer. (Baxter J Clin Oncol 2021 ASCO guideline) [Finally, several reasons support our decision to use long-course instead of short-course RT in both treatment arms. First, while preliminary data suggests short-course RT may also lead to significant chances for a pCR (particularly in the setting of consolidation chemotherapy), less is known about the chances of a cCR (primary endpoint of our study) [