Preoperative Intensification Treatment in Patients with Rectal Adenocarcinoma - A Standardization of Clinical Practice

Neoadjuvant radiotherapy with concurrent fluoropyrimidines followed by surgery is considered the standard-of-care in locally advanced rectal cancer (LARC). Neoadjuvant chemo-radiotherapy (CRT) is associated with a pathological complete response (pCR) rate of 11-18%. Intensification of neoadjuvant treatment can lead to higher rates of tumor resectability and pCR, although the best therapeutic sequence is unknown. This is a prospective, single arm study which aims to standardize institutional clinical practice in accordance with international recommendations. Patients with LARC received neoadjuvant intensive treatment with concurrent CRT followed by 12 weeks of consolidation chemotherapy (ChT) with CAPOX or mFOLFOX6. Clinical response was accessed by magnetic resonance imaging (MRI) at 10 weeks, 14 weeks, and 18 weeks. If complete clinical response (cCR) was obtained, a watch-and-wait (W&W) strategy was offered; otherwise, surgery was performed. The primary endpoint was to evaluate clinical response rate after 10 weeks of intensification treatment, and its comparison with historical data. Key secondary endpoints included clinical response rate at 14 and 18 weeks, rate of patients who enter W&W strategy, rate of pCR in patients who undergo surgery, recurrence free survival (RFS), overall survival (OS), and rate of adverse effects. We present efficacy and safety preliminary results one year from the start of the study. Six patients with LARC were included. Three had a tumour in the low-rectum, two in middle-rectum and one in high-rectum. At initial magnetic resonance imaging (MRI), two had cT2, three had cT3 and one had cT4; three had cN1 and one cN2; two patients had extramural venous invasion (EMVI+) and one had mesorectal fascia involvement (MRF+). After CRT, all patients started consolidation ChT. The most common grade [≥]3 AEs were neutropenia, nausea, and diarrhoea. There were no dose-limiting toxicities and all patients completed treatment. MRI at 10 weeks showed a tumour regression grade (TRG) 2 in three patients, TRG3 in two patients and TRG4 in one patient. Two patients are in the W&W surveillance protocol; one is awaiting MRI at 18 weeks; another patient awaits surgery; and of the two patients already underwent surgery, one had a ypT3N1 and the other had complete pathological response (pCR). To this date there are no recurrence or death events. These preliminary results suggests tolerability and feasibility of a neoadjuvant intensification treatment in patients with LARC. Categoriesrectal adenocarcinoma, oncology