Total Neoadjuvant Therapy Versus Conventional Chemoradiotherapy in Rectal Cancer: Impact on Tumor Regression Grade and the Predictive Value of CEA

<i>Background and Objectives</i>: The introduction of total neoadjuvant therapy (TNT) in the preoperative stage has been associated with improved oncological outcomes. However, TNT may lead to tissue fibrosis and be accompanied by increased difficulty during surgery. Additionally, predicting tumor response to neoadjuvant therapy is crucial for identifying patients who may achieve a complete pathological response (pCR) or qualify for organ-preserving strategies. The aim of this study is to evaluate the effect of TNT versus conventional chemoradiotherapy (CRT) on tumor regression grade (TRG) and the association between preoperative carcinoembryonic antigen (CEA) levels and good tumor response. A secondary endpoint is to investigate the effect of TNT on surgical difficulty, using indirect indicators like the quality of total mesorectal excision (TME), circumferential resection margin (CRM), and achievement of R0 resection. <i>Materials and Methods</i>: This is a retrospective, single-center study including 93 patients with locally advanced rectal cancer who received either TNT (<i>n</i> = 43) or CRT (<i>n</i> = 50). <i>Results</i>: The TNT group, compared to the CRT group, demonstrated a significantly higher rate of pCR (TRG0) (37.2% vs. 18%, <i>p</i> = 0.038) and good tumor regression (TRG 0-1) (53.5% vs. 28%, <i>p</i> = 0.019). Furthermore, patients with CEA < 5 ng/mL showed significantly higher rates of good tumor response (TRG 0-1) compared to those with CEA ≥ 5 ng/mL (45.3% vs. 16.7%, <i>p</i> = 0.032). When further categorized by treatment type, CEA levels did not demonstrate statistically significant differences Lastly, increased surgical difficulty could not be established, as no significant differences were observed in terms of positive CRM rates, R0 resection, and TME quality between groups. <i>Conclusions</i>: TNT was associated with improved TRG scores compared to CRT without increasing surgical difficulty. Lower pre-treatment CEAs were linked to better tumor response, irrespective of the type of treatment. These findings support the oncological benefit of TNT and suggest that CEA may have some predictive value for treatment response.