Evaluating complete response rates and predictors in total neoadjuvant therapy for rectal cancer

Background: There is a paradigm shift in the management of locally advanced rectal cancer (LARC) from conventional neoadjuvant treatment to total neoadjuvant therapy (TNT). Despite its growing acceptance, there are limited studies that have examined its effects on disease presentation. In addition, it is important to determine the factors that play a role in complete response (CR). Our previous data from 119 patients revealed that the CR rate was 37%, and low rectal tumors and the absence of extramural vascular invasion (EMVI) were predictors of CR. Unfortunately, there continues to be a lack of data, and reliable markers are still needed to consistently identify the best respondents. Therefore, this study aimed to determine the factors associated with CR. Moreover, this study hypothesized that both predictive factors and the CR ratio might evolve over time because of the growing patient population.

Methods: This retrospective study included patients who completed TNT for LARC at our tertiary care center between 2015 and 2022. The primary outcome was to determine the predictors of CR. The secondary outcomes were the 2-year disease-free survival (DFS) rate and overall survival (OS) rate. CR consists of patients who sustained clinical CR (cCR) for at least 12 months under watch and wait or had pathologic CR (pCR) after surgery.

Results: Of 339 patients with LARC, 208 (61.3%) successfully completed TNT. Among 208 patients, 57 (27.4%) achieved cCR, and 166 (80.0%) sustained cCR without tumor regrowth after 1 year. The remaining 151 patients (72.6%) underwent surgery, and 42 patients had pCR. The final CR rate was 42.3%. The median age of the patients was 56 years (IQR, 49-66). Moreover, 132 participants (63.5%) were male, whereas 76 participants (36.5%) were female. The median tumor size was 4.95 cm (IQR, 3.60-6.43), with most tumors in the low rectum (119 [57.2%]). Based on the MRI findings, the mesorectal facia (MRF) involvement rate was 25.0% (n = 52), and EMVI was observed in 43 patients (20.7%). Low rectal tumors, the absence of MRF involvement, and the absence of EMVI were predictors of CR. With a median follow-up of 24.7 months, 2-year DFS and OS were significantly higher among patients with CR than among patients with incomplete response (91.3% vs 71.0% [P < .01] and 98.8% vs 90.2% [P = .03], respectively).

Conclusion: An increasing CR rate was observed in our updated dataset compared with that in our previous study. In addition to previously identified predictors, low tumor location, and the absence of EMVI, the absence of MRF involvement was determined as a predictor of CR. Our findings offer valuable insights into clinical practice and help clinicians set clear expectations when counseling patients.