IntroductionIn the management of locally advanced rectal cancer (LARC), there is a paradigm shift from conventional neoadjuvant treatment to total neoadjuvant therapy (TNT). Despite its growing acceptance, there are limited studies have examined its effects on disease presentation. It is also important to determine the factors that play a role in complete response (CR). Our previous data with 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, we aimed to determine factors associated with CR. We hypothesized that due to the growing patient population, both predictive factors and CR ratio might evolve over time. MethodsA retrospective analysis of patients who completed TNT for LARC at our tertiary care center between 2015 and 2022 was performed. Our primary outcome was to determine predictors of CR. As a secondary outcome, we evaluated the 2-year disease-free and overall survival rates. CR consists of patients who sustained clinical CR (cCR) for at least 12 months under WW or had pathological CR (pCR) after surgery. ResultsOut of 339 patients with LARC, 208 (61.3%) successfully completed TNT. Among them, 57 (27.4%) patients achieved cCR, and 80% sustained without tumor regrowth after a year. The remaining 151 (72.6%) patients underwent surgery, and 42 had pCR. The final CR rate was 42.3%. The median age of the patients was 56 (49-66), and 63.5% of the participants were male (n=132), while 36.5% were female (n=76). The median tumor size was 4.95cm (3.6-6.43), with most tumors in the low rectum (119, 57.2%). The MRF involvement rate was 25% (n=52), and EMVI was observed in 20.7% of patients (n=43). based on MRI findings. Low rectal tumors, the absence of MRF involvement, and the absence of EMVI were predicted CR. With a median follow-up of 24.7 months, 2-year disease-free survival and overall survival were significantly higher among patients with CR (91.3% vs 71%, p<0.01 and 98.8% vs 90.2% p=0.03, respectively). ConclusionIn our updated dataset, we observed an increasing CR rate compared to our previous study. In addition to previously identified predictors, low tumor location and the absence of EMVI, we also found the absence of MRF involvement as a predictor of CR. These findings offer valuable insights for clinical practice, helping clinicians set clear expectations when counseling patients.