Assessment of response to total neoadjuvant therapy in carcinoma rectum: A real-world prospective observational study from eastern India.

Background: Preoperative chemoradiotherapy and subsequent surgery is the standard of care for locally advanced rectal cancer. This has resulted in good local control, but without a significant survival benefit. Multiple randomised trials have utilised total neoadjuvant therapy (TNT) to improve survival outcomes. However, clinical experience in India is limited.

Methods: Patients with cT3/4 or N + rectal adenocarcinoma with ECOG 0-1 were included. Treatment course comprised Short-course radiotherapy (25 Gy in 5 fractions over 1 week), followed by 6 cycles of chemotherapy (Inj. oxaliplatin 130 mg/m2 on D1 and Tab capecitabine 1000 mg/m2 BID from D1-14, q21 days). Following the completion of neoadjuvant treatment, patients were assessed for surgery. Surgery involved Total Mesorectal Excision.

Results: 32 patients were enrolled. Males comprised 66% of the population, and the median age was 42 years. 75% of patients had distal rectal tumours. 18.8% were signet ring cell carcinoma (SRC). 43.8% of patients had mesorectal fascia involvement and lateral lymph nodes (LLN) were present in 28% patients. All patients completed the full course of TNT. 84.4% patients underwent definitive surgery. Pathological complete response was reported in 37% patients, with R0 resection in 96%. Sphincter preservation could be achieved in 29.2% of distal tumours. The incidence of acute grade 3 or higher adverse events was 40.6%, the most common being diarrhoea (15.6%), followed by anaemia (9.4%). Post-operative complications were seen in 22.2% of patients, the most frequent being delayed wound healing. The incidence of Clavien-Dindo grade IV complications was 3.7%. At a median follow-up of 2 years, OS and PFS were 75% and 59.4%, respectively. Absence of LLN and non-SRC histology was associated with significantly higher PFS and OS.

Conclusion: The TNT protocol we followed was well tolerated in our patient population. Excellent tumour and nodal regression rates were seen. It can be considered a viable alternative to preoperative conventional chemoradiation, particularly in a resource-limited setting. However, this treatment strategy was not optimal for patients with high-risk features such as the presence of LLNs and SRC histology.