Abstract
INTRODUCTION: Multimodal treatment represents the standard of care for rectal adenocarcinoma. A subset of patients achieves a pathological complete response (pCR), while a different subset does not. While pCR is associated with improved overall survival (OS), non-responders suffer from not being treated in a way tailored to their needs and have worse overall survival. PURPOSE: To evaluate the factors responsible for pCR and tumor cell dedifferentiation. Additionally, the prognosis of patients with pCR and tumor cell dedifferentiation and the clinical impact of dedifferentiation. RESULTS: The factor responsible for pCR was clinically negative lymph node status (cN0). The incidence of dedifferentiation of tumor cells was statistically significantly higher in the group of patients who were not treated with FOLFOX/FOLFIRI chemotherapy (p = 0.033), had cN1 lymph node status (p = 0.010), and primary tumor grade 2 (p < 0.0001). The clinical impact demonstrated an association between dedifferentiation and more advanced pT (p = 0.026) and pTNM stage (p = 0.035). Parameters identified as significant negative predictors of survival were: generalization (p = 0.01, HR 1.959, 95%CI 1.171–3.276), tumor budding (p = 0.001, HR 3.391, 95%CI 1.611–7.136), perineural spread (p = 0.015, HR 2.056, 95%CI 1.150–3. 676), number of positive lymph nodes (p = 0.047, HR 1.100, 95%CI 1.001–1.210), definitive pN (pN1 p = 0.003, HR 2.008, 95%CI 1.268–3.180), and stage III and IV (p = 0.037, HR 2.050, 95%CI 1.044–4.025, p = 0.001, HR 5.482, 95%CI 2.063–14.56). CONCLUSION: The genetics and biological characteristics of cancer cells make rectal cancer more challenging to treat. This shows why patients need personalized therapy.