Top Line: Are there differences in survival outcomes when non-operative management is offered rather than mandatory surgery following total neoadjuvant therapy for locally advanced rectal cancer.
The Study: TNT improves survival outcomes in patients with resectable, locally advanced rectal cancer. Improved response rates have also led to increasing interest in non-operative management especially in patients who may require an abdominoperineal resection. However, there is limited direct comparison between the standard operative approach and non-operative management. OPRA and CAO/ARO/AIO-12 were both prospective, phase 2 trials that randomized patients with locally advanced rectal cancer to different TNT sequences prior to surgery (chemoradiation followed by chemo versus chemo followed by chemoradiation). Both found that chemoradiation followed by chemo resulted in higher pathologic complete response rates. While CAO/ARO/AIO-12 required all patients to proceed to surgery 6 weeks after TNT, OPRA allowed non-operative management for those with complete or near-complete response to TNT. This study performed a pooled analysis of 628 patients from both studies (51.6% from OPRA, 48.4% from CAO/ARO/AIO-12) to compare survival outcomes. They found no differences in local recurrence free survival, disease free survival, or overall survival between studies. There were also no differences in these outcomes when comparing TNT sequencing across trials.
TBL: This pooled analysis of two prospective trials suggests that non-operative management in appropriately selected patients does not compromise survival outcomes when compared to mandatory surgery following TNT for rectal cancer. | Williams, Ann Oncol 2025
The Study: TNT improves survival outcomes in patients with resectable, locally advanced rectal cancer. Improved response rates have also led to increasing interest in non-operative management especially in patients who may require an abdominoperineal resection. However, there is limited direct comparison between the standard operative approach and non-operative management. OPRA and CAO/ARO/AIO-12 were both prospective, phase 2 trials that randomized patients with locally advanced rectal cancer to different TNT sequences prior to surgery (chemoradiation followed by chemo versus chemo followed by chemoradiation). Both found that chemoradiation followed by chemo resulted in higher pathologic complete response rates. While CAO/ARO/AIO-12 required all patients to proceed to surgery 6 weeks after TNT, OPRA allowed non-operative management for those with complete or near-complete response to TNT. This study performed a pooled analysis of 628 patients from both studies (51.6% from OPRA, 48.4% from CAO/ARO/AIO-12) to compare survival outcomes. They found no differences in local recurrence free survival, disease free survival, or overall survival between studies. There were also no differences in these outcomes when comparing TNT sequencing across trials.
TBL: This pooled analysis of two prospective trials suggests that non-operative management in appropriately selected patients does not compromise survival outcomes when compared to mandatory surgery following TNT for rectal cancer. | Williams, Ann Oncol 2025