Total Neoadjuvant Therapy for Locally Advanced Rectal Carcinoma: A Multicentric Randomized Controlled Trial

Colorectal cancer is one of the fastest-growing and increasingly reported neoplasms in India, and the rectum is the most common subsite. In India, it’s the fourth most common cause of cancer in males (6.4%) and fifth most common cause of cancer in female (3.4%). Patients having locally advanced rectal carcinoma (LARC) especially with clinical subset T3 or T4 are at high risk of both local recurrence and distant metastasis. These patients are managed with a multidisciplinary approach and preoperatively fluoropyrimidine (5-fluorouracil or capecitabine) based chemo-radiotherapy followed by total meso-rectal excision (TME) has become the standard of care in LARC. Although there is a decrease in local recurrence, the improvement in overall survival is still unclear.Trial have failed to show any improvement with an intensification of chemotherapy and sequencing it with radiotherapy around surgery. Despite increased toxicity, there is no survival benefit following the addition of oxaliplatin on concurrent fluoropyrimidine in preop CRT. To avoid the toxicity of adjuvant chemotherapy, it has been suggested to add induction chemotherapy before CRT, but it fails to improve any survival benefit compared to standard therapy. Studies have shown that Capecitabine and oxaliplatin combination in an adjuvant setting, is safe and feasible in patients with LARC. The addition of Capecitabine and oxaliplatin as consolidation chemotherapy has shown to be beneficial in terms of pathological complete response and early initiation of systemic therapy. Other benefits include reduced chances of a positive distal resection margin, early treatment of micro-metastasis, de-escalation of adjuvant therapy, and early closure of proximal diversion stoma.