Immunotherapy-Enhanced Total Neoadjuvant Therapy Shows Promise for Organ Preservation in Early Rectal Cancer
核心洞察
The multicenter TORCH-E trial demonstrated that immunotherapy-based total neoadjuvant therapy achieved a 72.7% complete response rate and 60.6% organ preservation rate in early low rectal cancer (搜索) patients.
A separate retrospective study found that total neoadjuvant therapy achieved a 93.7% complete response rate and preserved organs in 87.5% of stage I rectal cancer (搜索) cases over a median 20-month follow-up.
Both studies suggest that total neoadjuvant therapy may offer a viable alternative to radical surgery for select patients with early-stage rectal cancer (搜索), particularly those with low-lying tumors where conventional surgery often results in permanent stoma.
Total neoadjuvant therapy (TNT) is emerging as a promising organ-preserving treatment option for patients with early-stage rectal cancer (搜索), with two recent studies demonstrating encouraging response rates and the potential to avoid radical surgery in select patients.
TORCH-E Trial Demonstrates Immunotherapy Enhancement
The multicenter, open-label, phase II TORCH-E trial explored an innovative immunotherapy-based total neoadjuvant therapy (iTNT) approach in patients with early low rectal cancer (搜索). The study enrolled 33 patients with histologically confirmed rectal adenocarcinoma (搜索) located within 5 cm of the anal verge, staged T2–T3b N0, where sphincter-preserving options are often limited.
The treatment protocol involved short-course radiotherapy (25 Gy in 5 fractions) followed by four cycles of CAPOX (capecitabine + oxaliplatin) combined with the anti-PD-1 (搜索) antibody toripalimab. Patients achieving clinical complete response were offered a "watch-and-wait" pathway or local excision, while those with residual disease were advised to undergo total mesorectal excision.
Following iTNT, 16 patients achieved clinical complete response and proceeded with the watch-and-wait strategy. Among surgical patients, pathologic complete response was observed in 8 of 8 patients who received local excision and in 5 of 9 patients treated with total mesorectal excision. This corresponded to a total complete response rate of 72.7% (24 of 33 patients) and an organ-preservation rate of 60.6%.
After a median follow-up of 24.1 months, five recurrence events were documented—four local regrowths and one metastatic recurrence. All cases of local regrowth were successfully managed with salvage TME, preserving overall disease control. The most frequent grade 3–4 adverse event was thrombocytopenia (27.3%), with no treatment-related deaths occurring.
Retrospective Analysis Confirms High Response Rates
A separate retrospective study published in Langenbeck's Archives of Surgery analyzed 16 patients with stage I rectal cancer (搜索) who declined total mesorectal excision and underwent TNT between 2015 and 2023. The study achieved a 93.7% complete response rate and 87.5% organ preservation rate, with no local recurrences observed over a median 20-month follow-up.
Among 11 patients who received TNT following partial response to chemoradiation, 9 (82%) achieved complete clinical response. In the group of 5 patients who received TNT after local excision, no local recurrence or distant metastasis was observed during follow-up.
"Our findings suggest that TNT may be a viable organ-preserving alternative for select patients with early-stage rectal cancer (搜索), particularly for low-lying tumors where conventional surgery often results in a permanent stoma," wrote the researchers.
Clinical Implications and Future Directions
Both studies highlight the potential of TNT to shift treatment paradigms in early rectal cancer (搜索) management. The TORCH-E results suggest that immune-based priming can amplify tumor regression even in microsatellite-stable early rectal cancers, offering a path toward organ-sparing management and better postoperative quality of life.
However, researchers acknowledge limitations including small sample sizes and relatively short follow-up periods. The retrospective study's authors noted that "reduced-dose TNT may be considered a potential treatment option for early-stage rectal cancer (搜索) patients in the future," while emphasizing that "larger prospective trials with various treatment protocols and extended follow-up periods are essential to validate the efficacy of TNT in patients with stage I rectal cancer (搜索)."
The TORCH-E investigators similarly called for validation in a larger, randomized phase III trial to confirm long-term oncologic outcomes and refine patient-selection criteria. These findings represent a significant step toward redefining rectal cancer (搜索) care for select patients, moving from radical resection toward functional cure with preserved organ integrity.