Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

ARTICLE HIGHLIGHTS

Research background

Distant metastases remain the leading cause of death for patients with locally advanced rectal cancer. Systemic chemotherapy that mainly affects micrometastasis is administered with chemoradiotherapy prior to surgery in total neoadjuvant treatment.

Research motivation

Currently, it is unknown which treatment is better for patients with locally advanced rectal cancer and high-risk factors for treatment failure.

Research objectives

To compare the results of total neoadjuvant therapy and standard therapy in patients with locally advanced rectal cancer and high-risk factors for failure in the same time period.

Research methods

We selected patients with locally advanced rectal cancer and high-risk factors for failure who were treated with standard therapy or with total neoadjuvant therapy. High-risk for failure were defined by the presence of at least one of the following factors: T4 status; N2 status; positive mesorectal fascia; extramural vascular invasion; and/or positive lateral lymph node.

Research results

This retrospective study showed that total neoadjuvant therapy yielded a higher proportion of pathological complete response (pCR), lower neoadjuvant rectal score, higher T-and N-downstaging, equivalent R0 resection, shorter time to stoma closure, higher compliance during systemic chemotherapy, lower proportion of acute toxicity grades ≥ 3 during chemotherapy, and equivalent acute toxicity and compliance during chemoradiotherapy and in the postoperative period. With total neoadjuvant therapy, we achieved a statistically significantly higher rate of pCR with intensity-modulated radiotherapy/volumetric modulated arc therapy compared to the three-dimensional conformal radiation therapy technique.

Research conclusions

The outcome of total neoadjuvant therapy is better than that of standard treatment of locally advanced rectal cancer with high-risk factors for failure, in terms of the pCR rate and the neoadjuvant rectal prognostic score.

Research perspectives

Randomized studies are needed to more reliably assess the benefits of total neoadjuvant therapy for locally advanced rectal cancer with high-risk factors for failure.