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

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.

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.

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.

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.