From the Guidelines
Total neoadjuvant chemoradiation (TNCR) is the preferred approach for stage II-III rectal cancer, as it has been shown to improve pathologic complete response rates and disease-free survival compared to partial neoadjuvant chemoradiation. The main difference between TNCR and partial neoadjuvant chemoradiation lies in the timing and completeness of the chemotherapy regimen. TNCR involves administering all planned chemotherapy and radiation therapy before surgery, typically including both chemoradiation (5-FU or capecitabine with radiation) and additional cycles of systemic chemotherapy (usually FOLFOX or CAPOX) in the neoadjuvant setting [ 1 ]. In contrast, partial neoadjuvant chemoradiation traditionally delivers only the chemoradiation component before surgery, with remaining systemic chemotherapy given after surgical resection (adjuvant setting).
The benefits of TNCR include higher rates of pathologic complete response (pCR) and longer disease-free survival (DFS), minimizing the length of time patients need an ileostomy, facilitating resection, and improving the tolerance and completion rates of chemotherapy [ 1 ]. The NCCN panel recommends TNCR as the preferred approach for stage II-III rectal cancer [ 1 ]. Additionally, the ASCO guideline recommends total neoadjuvant therapy (TNT) for patients with microsatellite stable or proficient mismatch repair locally advanced rectal cancer, with the preferred timing for chemotherapy being after radiation [ 1 ].
Some key points to consider when implementing TNCR include:
- The TNCR approach typically involves 5-6 weeks of chemoradiation (using capecitabine 825 mg/m² twice daily or 5-FU infusion with 45-50 Gy radiation) followed by 3-4 months of systemic chemotherapy (FOLFOX: 5-FU, leucovorin, oxaliplatin or CAPOX: capecitabine, oxaliplatin) before surgery, or the reverse sequence.
- This approach is particularly beneficial for patients with locally advanced disease (T3-4 or node-positive) where tumor downstaging is crucial.
- Careful multidisciplinary coordination is required to monitor treatment response and determine optimal timing for surgery.
- Non-operative management may be discussed as an alternative to total mesorectal excision for patients who have a clinical complete response to neoadjuvant therapy [ 1 ].
From the Research
Total Neoadjuvant Chemoradiation (TNCR) vs Partial Neoadjuvant Chemoradiation in Rectal Cancer
- The main difference between total neoadjuvant chemoradiation (TNCR) and partial neoadjuvant chemoradiation in the treatment of rectal cancer lies in the timing and duration of chemotherapy and radiation therapy administration.
- TNCR involves the administration of both chemotherapy and radiation therapy before surgery, whereas partial neoadjuvant chemoradiation may involve a shorter course of radiation or chemotherapy before surgery.
Efficacy of TNCR vs Partial Neoadjuvant Chemoradiation
- A study published in The British journal of surgery 2 found that total neoadjuvant therapy with long-course chemoradiotherapy or short-course radiotherapy improved the pathological complete response rate compared to long-course chemoradiotherapy alone.
- Another study published in the Journal of gastrointestinal surgery 3 found that total neoadjuvant therapy with either induction chemotherapy and chemoradiation or short-course radiotherapy followed by consolidative chemotherapy were associated with similar perioperative morbidity and complete response rates.
Clinical Outcomes
- A study published in the World journal of surgery 4 reported the long-term outcome of local excision after complete pathological response to neoadjuvant chemoradiation therapy for rectal cancer, with no local or distant recurrences detected in the remaining 20 patients after a median follow-up of 87 months.
- A study published in the Journal of the Chinese Medical Association 5 found that neoadjuvant concurrent chemoradiotherapy led to a high percentage of R0 resection and a low recurrence rate in locally advanced rectal cancer patients.
- A study published in Medicine 6 found that tumor length >4 cm was associated with decreased rate of pathological complete response in locally advanced rectal cancer patients who had chemoradiotherapy followed by surgery.
Predictive Factors for Pathological Complete Response
- The study published in Medicine 6 also found that complete clinical response was significantly associated with higher rate of pathological complete response.
- The study published in The British journal of surgery 2 found that long-course chemoradiotherapy with consolidation chemotherapy exhibited higher disease-free survival than long-course chemoradiotherapy alone.