Background and Objective: In the therapeutic strategy of rectal cancer, radiotherapy has consolidated its important position and frequent use in current practice due to its indications as neoadjuvant, adjuvant, definitive, or palliative treatment. In recent years, total neoadjuvant therapy (TNT) has been established as the preferred regimen compared to concurrent neoadjuvant chemoradiotherapy (CRT). In relation to better outcomes, the percentage of patients who achieved pathological complete response (pCR) after neoadjuvant treatment is higher in the case of TNT. This study aimed to analyze the response to TNT compared to neoadjuvant CRT regarding pCR rate and the change in staging after surgical intervention. Materials and Methods: We performed a retrospective study on 323 patients with rectal cancer and finally analyzed the data of 201 patients with neoadjuvant treatment, selected based on the inclusion and exclusion criteria. Patients received CRT neoadjuvant therapy or TNT neoadjuvant therapy with FOLFOX or CAPEOX. Results: Out of 157 patients who underwent TNT treatment, 19.74% had pathological complete response, whereas in the group with CRT (n = 44), those with pCR were 13.64%. After neoadjuvant treatment, the most frequent TNM classifications were ypT2 (40.30%) and ypN0 (79.10%). The statistical analysis of the postoperative disease stage, after neoadjuvant therapy, showed that the most frequent changes were downstaging (71.14%) and complete response (18.41%). Only four patients (1.99%) had an upstaging change. The majority of patients (88.56%) initially presented clinical evidence of nodal involvement whereas only 20.9% of the patients still presented regional disease at the time of surgical intervention. Conclusions: By using TNT, a higher rate of stage reduction is obtained compared to the neoadjuvant CRT treatment. The post-neoadjuvant-treatment imagistic evaluation fails to accurately evaluate the response. A better response to TNT was observed in young patients.

Background and Objectives: Rectal cancer is a major cause of morbidity and mortality worldwide, and although current therapeutic protocols have improved survival, treatment-related toxicities may significantly affect patients’ daily functioning and emotional well-being. This study aimed to prospectively assess the impact of radiotherapy with concurrent capecitabine on functional and symptomatic outcomes in patients with rectal cancer, with a particular focus on the presence of a stoma and treatment strategy. Materials and Methods: From 165 patients initially assessed, 64 were included in this study after applying eligibility criteria. All received pelvic radiotherapy (50.4 Gy in 28 fractions); 62.5% also received CAPOX chemotherapy. The quality of life was assessed using EORTC QLQ-C30 and QLQ-CR29 questionnaires administered at three time points: before treatment, mid-treatment (day 15), and post-treatment. Results: A statistically significant deterioration was observed in physical, emotional, social, and role functioning over the course of treatment, along with an increase in symptom scores for fatigue, pain, gastrointestinal, and urinary complaints. The presence of a stoma was significantly associated with worse gastrointestinal symptoms and emotional functioning. No significant differences were noted between patients with or without chemotherapy. Despite symptom worsening, global quality-of-life scores remained relatively stable. Conclusions: These findings highlight the complex interplay between treatment toxicity and patient adaptation. The presence of a stoma and other clinical or demographic factors significantly influence patients’ experience during therapy. Integrating routine assessment of functional and symptomatic burden into clinical practice could support individualized interventions aimed at maintaining daily functioning and psychological resilience during treatment.

Background: Total neoadjuvant therapy (TNT) is increasingly administered in rectal cancer, but compared with concurrent chemoradiotherapy (CRT), data regarding the gastrointestinal (GI) toxicity profile and clinical predictors remain limited. Objectives: To evaluate GI toxicity associated with TNT compared with CRT and to explore clinical predictors of these adverse events (AEs). Methods: This retrospective study included 201 patients with rectal cancer treated with TNT (n = 157) and CRT (n = 44). GI AEs (nausea, vomiting, diarrhea) were graded according to CTCAE v5.0. In the analysis of factors associated with GI AEs, multiple clinical and pathological variables were included using multivariable logistic regression. Results: The composite endpoint “any GI AEs grade ≥ 1” was more frequent in the TNT group compared with the CRT group (33.1% vs. 15.9%; RR = 2.08; 95% CI 1.02–4.25; p = 0.038). Nausea was significantly more frequent in the TNT group (28.7% vs. 9.1%; RR = 3.15; 95% CI 1.20–8.30; p = 0.012), whereas vomiting (9.6% vs. 2.3%; p = 0.203) and diarrhea (17.8% vs. 9.1%; p = 0.242) did not reach statistical significance. In multivariable logistic regression, TNT (OR = 2.65; 95% CI 1.08–6.53; p = 0.032) and female sex (OR = 2.03; 95% CI 1.05–3.77; p = 0.033) were identified as independent predictors of grade ≥ 1 GI AEs. For nausea, TNT remained significant (OR = 4.37; 95% CI 1.45–13.20; p = 0.0089). Upper rectal tumor location was significantly associated with vomiting (p = 0.0054). No grade 3–4 GI AEs were observed in either treatment group. Conclusions: TNT was associated with a higher incidence of mild GI AEs, predominantly driven by nausea, without an increase in severe toxicities. TNT and female sex were identified as independent clinical predictors of an increased risk of GI AEs, while tumor location in the upper third of the rectum was associated with a higher occurrence of vomiting.