From the Guidelines
Total neoadjuvant therapy (TNT) is recommended for patients with locally advanced rectal cancer, as it improves pathologic complete response rates and overall survival compared to traditional neoadjuvant chemoradiation therapy (CRT) alone. TNT involves administering both chemotherapy and radiation therapy before surgery, typically including regimens such as FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) for systemic chemotherapy, combined with radiation therapy (either long-course chemoradiation with 45-50.4 Gy over 5-6 weeks with concurrent 5-FU or capecitabine, or short-course radiation with 25 Gy over 5 days) 1.
Key Benefits of TNT
- Improves pathologic complete response rates (20-30% versus 10-15% with traditional approaches) 1
- Improves overall survival (HR, 0.78 [95% CI, 0.62 to 0.97]) 1
- May enhance disease-free survival, although results are mixed (HR, 0.86 [95% CI, 0.71 to 1.04]) 1
- Allows earlier delivery of systemic therapy to address potential micrometastatic disease
- Improves treatment compliance and can facilitate organ preservation strategies
Patient Selection
TNT is particularly beneficial for patients with:
- Locally advanced disease (T3-T4 or node-positive)
- High-risk features
- Cases where downstaging would significantly improve surgical outcomes
Side Effects and Considerations
- Typical chemotherapy toxicities (neuropathy, fatigue, diarrhea)
- Radiation effects (proctitis, dermatitis)
- Increased grade 3 or 4 adverse events during preoperative therapy (RR, 1.56 [95% CI, 1.18 to 2.07]) 1
- Potential for increased late grade 3 to 4 complications, although results are mixed (RR, 1.43 [95% CI, 0.76 to 2.69]) 1
Current Guidelines and Recommendations
The American Society of Clinical Oncology (ASCO) recommends TNT as initial treatment for patients with tumors located in the lower rectum and/or patients who are at higher risk for local and/or distant metastases 1. The National Comprehensive Cancer Network (NCCN) also recommends TNT as an option for patients with locally advanced rectal cancer, with consideration of patient selection and sequencing of therapy 1.
From the Research
Total Neoadjuvant Therapy (TNT) for Rectal Cancer
- Total Neoadjuvant Therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC) that delivers both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery 2.
- The efficacy and safety of TNT remain controversial in randomized controlled trials (RCTs), but recent studies suggest that it may improve pathologic complete response (pCR) rates, disease-free survival (DFS), and overall survival (OS) compared to standard neoadjuvant chemoradiotherapy 2, 3, 4, 5.
Benefits of TNT
- TNT has been shown to improve pCR rates, with a statistically significant improvement in pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005) 2.
- TNT also shows improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15) 2.
- Additionally, TNT treatment shows significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012) 2.
Comparison with Standard Treatment
- A meta-analysis of RCTs found that TNT had a higher pathological complete response rate (risk ratio [RR] = 1.65,95% CI: [1.40,1.94], p < 0.00001) and higher 3-year overall survival (hazard ratio [HR] = 0.81,95% CI: [0.67,0.98], p = 0.03) compared to standard neoadjuvant chemoradiotherapy 5.
- Another study found that TNT facilitated delivery of planned systemic therapy and had a higher complete response (CR) rate, including both pathologic CR (pCR) and sustained clinical CR (cCR), compared to standard treatment 3.