From the Guidelines
Total Neoadjuvant Therapy (TNT) is a recommended treatment approach for locally advanced rectal cancer, as it has been shown to improve adherence, decrease the occurrence of distant metastases, and ultimately improve overall survival, according to the most recent guidelines from the Journal of Clinical Oncology 1.
Key Components of TNT
- The standard TNT regimen typically includes 3-4 months of induction chemotherapy with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin)
- Followed by chemoradiation with either 5-fluorouracil or capecitabine as a radiosensitizer
- The radiation component usually involves 45-50.4 Gy delivered over 5-6 weeks
Benefits of TNT
- Higher rates of pathologic complete response (15-30%)
- Improved tumor downstaging
- Better sphincter preservation
- Reduced risk of distant metastases
- Improved treatment compliance since chemotherapy is delivered before radiation-induced pelvic inflammation occurs
Recent Updates and Recommendations
- The NCCN Guidelines for Rectal Cancer have been updated to include the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, and updates to the total neoadjuvant therapy approach based on the results of recent clinical trials 1
- A "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy has also been added
Important Considerations
- Potential side effects of TNT include neuropathy from oxaliplatin, diarrhea, fatigue, and radiation-related bowel and bladder symptoms
- Regular monitoring with blood tests, imaging, and clinical assessments is essential throughout treatment to manage toxicities and assess response
- Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended to balance curative-intent therapy with minimal impact on quality of life 1
From the Research
Role of Total Neoadjuvant Therapy (TNT) in Rectal Cancer
- Total Neoadjuvant Therapy (TNT) is a treatment approach for rectal cancer that involves the use of neoadjuvant chemoradiotherapy followed by chemotherapy before surgery 2.
- The efficacy of TNT in treating locally advanced rectal cancer has been supported by studies, with a pathologic complete response (pCR) rate of 21% and near-complete response in nearly half of the patients with locally advanced rectal cancer 2.
- TNT has been shown to be effective in achieving local control and improving overall survival in patients with rectal cancer, with studies suggesting that it can be used as an alternative to traditional treatment approaches 3, 2, 4.
Predictors of Response to TNT
- Several factors have been identified as independent predictors of overall complete response (CR) after TNT, including N-stage, circumferential resection margin (CRM) status, average vascularity (AV), surgical procedure, and postoperative tumor size 2.
- Patients with N2 disease have been shown to have a lower chance of achieving CR, while positive CRM is linked to a reduction in the probability of CR 2.
- The choice of surgical procedure, with patients who undergo anterior resection (AR) having a greater chance of achieving CR than those who undergo abdominoperineal resection (APR), is also a significant predictor of response to TNT 2.
Comparison with Other Treatment Approaches
- TNT has been compared to other treatment approaches, including long-course preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy, with studies suggesting that it can be an effective alternative 5, 4.
- The use of capecitabine and radiotherapy as neoadjuvant treatment for rectal cancer has also been explored, with studies showing that it can be as effective as 5-fluorouracil (5-FU)-based neoadjuvant chemoradiotherapy 6.
- Emerging trends in the treatment of rectal cancer, including the selective use of pelvic radiation and the role of radiation for a positive radial margin, are also being investigated 5.