From the Guidelines
Total neoadjuvant therapy (TNT) for rectal cancer is a treatment approach that delivers all chemotherapy and radiation therapy before surgery, and is recommended as the preferred approach for stage II-III rectal cancer due to its benefits in improving pathologic complete response rates and disease-free survival.
Key Components of TNT
- A typical TNT regimen includes 5-6 months of systemic chemotherapy (such as FOLFOX: 5-fluorouracil, leucovorin, and oxaliplatin or CAPOX: capecitabine and oxaliplatin)
- Chemoradiation (typically 5.5 weeks of radiation with concurrent 5-fluorouracil or capecitabine), all given before surgical resection of the tumor 1
Advantages of TNT
- Treats potential micrometastatic disease earlier
- Improves patient compliance with systemic therapy
- Increases rates of pathologic complete response (15-30% of patients may have no viable tumor cells at surgery)
- Potentially allows for organ preservation in select patients who have a complete clinical response
- May downstage tumors more effectively, making sphincter-preserving surgery possible for more patients with low-lying rectal cancers 1
Patient Selection
- Particularly beneficial for patients with locally advanced disease (T3-T4 or node-positive) who have higher risk of both local recurrence and distant metastasis
- Recommended as the preferred approach for stage II-III rectal cancer by the NCCN panel 1
From the Research
Definition of Total Neoadjuvant Therapy
Total neoadjuvant therapy (TNT) is a treatment strategy for rectal cancer that involves administering both chemoradiotherapy and systemic chemotherapy before surgery 2. This approach aims to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes.
Components of Total Neoadjuvant Therapy
TNT regimens typically consist of:
- Chemoradiotherapy, which may include short-course or long-course radiotherapy
- Systemic chemotherapy, which may involve induction or consolidation chemotherapy
- Various combinations of chemotherapy agents, such as fluorouracil, oxaliplatin, and leucovorin 3, 4
Goals and Benefits of Total Neoadjuvant Therapy
The primary goals of TNT are to:
- Achieve clinical complete response or pathological complete response
- Preserve organs and avoid surgery whenever possible
- Improve disease-free survival and overall survival rates
- Enhance treatment outcomes for patients with locally advanced rectal cancer 5, 6
Treatment Outcomes and Organ Preservation
Studies have shown that TNT can result in:
- High rates of clinical complete response and pathological complete response
- Improved disease-free survival and overall survival rates
- Successful organ preservation in a significant proportion of patients
- Acceptable toxicity profiles, with manageable side effects 4, 6
Key Considerations and Future Directions
- The optimal TNT regimen and treatment strategy remain to be determined
- Ongoing research and clinical trials are needed to further evaluate the efficacy and safety of TNT
- Personalized treatment approaches and multidisciplinary decision-making are crucial for optimizing outcomes in rectal cancer patients 2, 5