What is the chance of complete response (CR) with total neoadjuvant therapy in rectal cancer?

From the Guidelines

Total neoadjuvant therapy (TNT) for rectal cancer achieves complete response (CR) rates of approximately 71-76%, as reported in the OPRA trial, which is the most recent and highest quality study available 1.

Key Points

• TNT typically involves administering both chemotherapy and radiation therapy before surgery, rather than the traditional approach of giving some treatment before and some after surgery.
• A common TNT regimen includes 4 months of FOLFOX or CAPOX chemotherapy (5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) combined with long-course chemoradiation (typically 5.5 weeks of radiation with concurrent 5-FU or capecitabine).
• The higher CR rates with TNT are attributed to earlier delivery of systemic therapy, which may address micrometastatic disease sooner and enhance the effects of radiation.
• Patients achieving complete clinical response may be candidates for a "watch and wait" approach with close surveillance, potentially avoiding surgery altogether, though this requires careful patient selection and regular monitoring, as outlined in the ASCO guideline 1.

Important Considerations

• The definition of clinical complete response (cCR) is crucial in determining eligibility for nonoperative management (NOM), and should be based on digital rectal examination, rectoscopy, and MRI findings, as defined in the ASCO guideline 1.
• The surveillance protocol for patients undergoing NOM should include regular digital rectal examinations, flexible sigmoidoscopy, and rectal MRI, as outlined in the OPRA trial 1.
• Immunotherapy may be recommended for patients with MSI-H or dMMR rectal cancers, as an initial approach, compared to TNT or another treatment strategy, as outlined in the ASCO guideline 1.

From the Research

Chance of Complete Response with Total Neoadjuvant Therapy in Rectal Cancer

• The chance of complete response (CR) with total neoadjuvant therapy in rectal cancer is approximately 37% 2.
• A study found that 38 out of 102 patients (37%) had a complete response, including 15 out of 18 (83%) nonoperative patients who remained cancer-free and 23 out of 84 (27%) patients who underwent surgery and had a pathological complete response 2.
• Another study reported a complete response rate of 31.6% in patients who received total neoadjuvant therapy (TNT) compared to 22.3% in patients who received neoadjuvant chemoradiation (NCRT) 3.
• A systematic review found that the overall pathological complete response rate following neoadjuvant long-course chemoradiotherapy for rectal cancer is approximately 20% 4.
• A study from Saudi Arabia reported a pathological complete response rate of 21% in patients with locally advanced rectal cancer who underwent short-course radiation therapy followed by oxaliplatin-based chemotherapy 5.

Predictors of Complete Response

• Younger age, normal carcinoembryonic antigen, clinical node-negative, smaller tumors, and wild-type p53 and SMAD4 are predictive features of a complete response 2.
• Pre-operative total neoadjuvant therapy (TNT) is a predictor of complete pathological response, while extramural vascular invasion (EMVI) is a predictor of lower rates of complete pathological response 3.
• N-stage, circumferential resection margin (CRM) status, average vascularity (AV) size, and surgical approach are significant predictors of complete response 5.