Comparison of Standard Neoadjuvant Therapy and Total Neoadjuvant Therapy in Terms of Effectiveness in Patients Diagnosed with Locally Advanced Rectal Cancer.

Abstract

Background/Objectives: The study aimed to compare the treatment effectiveness of patients with locally advanced rectal cancer undergoing standard neoadjuvant therapy or total neoadjuvant therapy. It also sought to identify prognostic factors for disease-free survival and overall survival and parameters predictive of pathological complete response. Materials and Methods: A retrospective analysis was conducted on 239 patients diagnosed with locally advanced rectal cancer between 2016 and 2022 at several medical centers in Turkey. Clinical data, including neoadjuvant chemoradiotherapy types, chemotherapy regimens, surgical outcomes, and survival metrics, were collected. Statistical analyses included chi-square tests, Kaplan-Meier survival analysis, and Cox proportional hazard models to evaluate prognostic factors for disease-free survival and overall survival and logistic regression to identify predictors of pathological complete response. Results: Among 239 patients, 46.9% received total neoadjuvant therapy, while 53.1% underwent standard neoadjuvant therapy. Total neoadjuvant therapy was associated with a significantly higher pathological complete response rate (45.5% vs. 14.9% in standard neoadjuvant therapy; p < 0.001) and longer disease-free survival (median 124.2 vs. 72.4 months). The 3-year overall survival rate for all patients was 90.7%, and disease-free survival was 76.8%. Multivariate analysis identified pathological complete response (HR: 2.34), total neoadjuvant therapy (HR: 5.12), and type of surgery (HR: 8.12) as independent prognostic factors for disease-free survival, and pathological complete response and absence of lymphovascular invasion as independent prognostic factors for overall survival. Logistic regression analysis showed that total neoadjuvant therapy (OR: 4.40) and initial neoadjuvant chemotherapy (OR: 2.02) were independent predictors of achieving pathological complete response. Conclusions: Total neoadjuvant therapy significantly improves pathological complete response rates, disease-free survival, and overall survival in patients with locally advanced rectal cancer compared to standard neoadjuvant therapy. Total neoadjuvant therapy and achieving pathological complete response are strong independent prognostic factors for both disease-free survival and overall survival, suggesting that a more intensive neoadjuvant approach may lead to better outcomes in locally advanced rectal cancer. The increased pathological complete responses rate with total neoadjuvant therapy has created an opportunity for the development of new treatment modalities and the advancement of non-surgical management strategies in the future.