From the Guidelines
The cure rate of total neoadjuvant therapy in stage 3 rectal cancer is significantly improved with a pathologic complete response rate of up to 35%, as supported by the most recent guidelines from the National Comprehensive Cancer Network (NCCN) in 2024 1. The total neoadjuvant therapy (TNT) approach has been gaining prominence in the treatment of clinical stage II or III rectal cancer, with benefits including higher rates of pathologic complete response (pCR) and longer disease-free survival (DFS) 1. Some key points about TNT include:
- Higher rates of pathologic complete response (pCR)
- Longer disease-free survival (DFS)
- Minimizing the length of time patients need an ileostomy
- Facilitating resection
- Improving the tolerance and completion rates of chemotherapy The NCCN panel recommends TNT as the preferred approach for stage II–III rectal cancer, as discussed in the NCCN guidelines 1. TNT involves administering both chemotherapy and radiation therapy before surgery, and has gained favor over the traditional strategy of surgery followed by adjuvant therapy because it can downstage tumors, increase the likelihood of R0 resection, improve sphincter preservation, and potentially allow for organ preservation in select patients with complete clinical response. The optimal sequencing of chemotherapy and radiation within the TNT approach continues to be studied, with some protocols administering induction chemotherapy first, while others use consolidation chemotherapy after chemoradiation. Based on the most recent evidence, TNT is the recommended approach for stage 3 rectal cancer, with the potential to improve cure rates and quality of life for patients 1.
From the Research
Cure Rate of Total Neoadjuvant Therapy in Stage 3 Rectal Cancer
- The cure rate of total neoadjuvant therapy in stage 3 rectal cancer is a topic of ongoing research, with several studies investigating its efficacy and safety 2, 3, 4, 5, 6.
- A study published in 2023 found that among 102 patients with stage 2 or 3 rectal adenocarcinoma, 38 (37%) patients had a complete response to total neoadjuvant therapy, including 15 of 18 (83%) nonoperative patients who remained cancer-free at a median of 22 months 2.
- Another study published in 2022 found that total neoadjuvant therapy was a predictor for complete pathological response in patients undergoing surgery for rectal cancer, with a complete response rate of 31.6% in patients who received total neoadjuvant therapy compared to 22.3% in patients who received neoadjuvant chemoradiation 3.
- A multicenter phase II clinical study published in 2017 found that neoadjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and levofolinate had a preoperative response rate of 48.8% and a pathologic complete response rate of 11.9% in patients with T3 or T4 stage II/III rectal cancer 4.
- A review article published in 2022 discussed the emerging approach of total neoadjuvant therapy for the treatment of locally advanced rectal cancer, highlighting its potential to reduce distant metastases and improve local control 6.
Predictive Factors for Complete Response
- Younger age, normal carcinoembryonic antigen, clinical node-negative, smaller tumors, and wild-type p53 and SMAD4 were found to be predictive of a complete response to total neoadjuvant therapy in one study 2.
- Total neoadjuvant therapy was found to be a predictor for complete pathological response in another study, while extramural vascular invasion was a predictor for lower rates of complete response 3.
Safety and Efficacy
- Neoadjuvant therapy with mFOLFOX6 was found to be safe and effective in a multicenter phase II clinical study, with a tolerable rate of postoperative complications 4.
- The addition of oxaliplatin to 5-FU-based chemoradiation has shown promising activity in early clinical trials, but phase III trials have been disappointing 5.