Predictive factors for early distant metastasis after neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Distant relapse is the leading cause of cancer-related death in locally advanced rectal cancer. Neoadjuvant chemoradiation (NACRT) followed by surgery inevitably delays delivery of systemic treatment. Some patients show early distant metastasis before systemic treatment.

To identify the most effective treatments. We investigated prognostic factors for distant metastasis, especially early distant metastasis, using the standard treatment paradigm to identify the most effective treatments according to recurrence risk.

From January 2015 through December 2019, rectal cancer patients who underwent NACRT for having clinical T 3-4 or clinical N 1-2 disease according to the 8^th American Joint Committee on Cancer staging system were included. Radiotherapy was delivered to the whole pelvis with concomitant chemotherapy. Patients received surgery 6-8 wk after completion of NACRT. Adjuvant chemotherapy was administered at the physician's discretion.

A total of 127 patients received NACRT. Ninety-three patients (73.2%) underwent surgery. The R0 resection rate was 89.2% in all patients. Pathologic tumor and node downstaging rates were 41.9% and 76.3%. Half the patients (n = 69) received adjuvant chemotherapy after surgery. The 3-year distant metastasis-free survival (DMFS) and overall survival (OS) rates were 81.7% and 83.5%. On univariate analyses, poorly differentiated tumors, > 5 cm, involvement of mesorectal fascia (MRF), or presence of extramural involvement (EMVI) were associated with worse DMFS and OS. Five patients showed distant metastasis at their first evaluation after NACRT. Patients with early distant metastasis were more likely to have poorly differentiated tumor (P = 0.025), tumors with involved MRF (P = 0.002), and EMVI (P = 0.012) than those who did not.

EMVI, the involvement of MRF, and poor histologic grade were associated with early distant metastasis. In order to control distant metastasis and improve treatment outcome, selective use of neoadjuvant treatment according to individualized risk factors is necessary. Future studies are required to determine effective treatment strategies for patients at high risk for distant metastasis.