Neoadjuvant Therapy in Locally Advanced Rectal Cancer-What Result Should We Expect?

Background and Objectives: Neoadjuvant chemoradiotherapy is a key component of the treatment strategy for locally advanced rectal cancer (LARC), both through its direct impact on oncological prognosis and by increasing the likelihood of sphincter-preserving surgery. Oncological prognosis improves dramatically following a complete pathological response to neoadjuvant therapy. Identifying predictors of response to neoadjuvant therapy has been a challenge over the past two decades, and these factors have not been fully identified. This study aimed to analyze the clinical, biological, and therapeutic factors associated with tumor response following neoadjuvant therapy in patients with locally advanced rectal cancer, with the aim of identifying independent predictors of the absence of a complete pathological response and optimizing personalized treatment strategies. Materials and Methods: This retrospective study included a cohort of 122 patients (81 men and 41 women), with a mean age of 63.5 years, diagnosed with locally advanced rectal cancer at two centers with expertise in colorectal surgery between January 2018 and December 2023. Patients received neoadjuvant treatment in two regimens: long-course chemoradiotherapy with oral radiosensitizing chemotherapy (82 patients) and total neoadjuvant therapy consisting of chemoradiotherapy followed by consolidation chemotherapy (40 patients). A series of clinical, biological, and therapeutic variables was analyzed for their association with pathological responses. Results: According to the Ryan score, the overall complete response rate following neoadjuvant therapy was 17.2%. pCR was observed more frequently in patients treated with total neoadjuvant therapy than in those treated with standard chemoradiotherapy. Elevated pre-treatment CEA levels were independently associated with a higher risk of unfavorable tumor response. The radiation dose and interval between completion of radiotherapy and surgery were significantly associated with tumor regression. Conclusions: These results underscore the importance of personalizing neoadjuvant therapy to improve cancer prognosis. Furthermore, optimizing tumor regression could lead to the potential expansion of sphincter-preserving resection techniques, which would have a direct and significant impact on the quality of life of these patients.