Fox Chase Cancer Center researchers have demonstrated that neoadjuvant chemotherapy followed by local excision may be a viable organ-preserving treatment option for patients with node-negative low rectal cancer, potentially sparing them from more extensive surgery and permanent colostomy bags.
Results from a phase II clinical trial (NCT03548961) presented at the Society of Surgical Oncology 2025 Annual Meeting showed that this approach achieved negative surgical margins in 79% of patients, with no local recurrences observed at a median follow-up of 26 months.
"As you can imagine, all patients would like to avoid, if possible, having a permanent colostomy. So when they're facing that surgical possibility, they really want to see if there's anything else that we can do," said Hannah Buettner, MD, a Complex General Surgical Oncology Fellow at Fox Chase, who presented the study findings.
Study Design and Patient Outcomes
The trial enrolled 19 patients with clinical stage T1-T3 low rectal adenocarcinoma whose imaging showed no evidence of cancer in their lymph nodes. Patients received up to six cycles of FOLFOX (leucovorin plus folinic acid, fluorouracil, and oxaliplatin) chemotherapy followed by MRI pelvis flex sigmoidoscopy to assess response.
Key findings included:
- 84% (16/19) of patients proceeded to local excision
- 79% (15/19) achieved the primary endpoint of negative margins
- 53% (10/19) experienced tumor downstaging
- 31% (5/19) achieved pathologic complete response
- No local recurrences were observed during the follow-up period
"Our results found that by pairing it with chemotherapy, local excision can be an appropriate level of surgery in more cases," Dr. Buettner explained. "There are a lot of benefits. It's a lower-risk procedure than total mesorectal excision, it has fewer side effects, and the recovery is shorter. The patient might be able to go home the same day as the procedure, as opposed to spending several days in the hospital with longer recovery."
Current Standard of Care vs. Organ Preservation
Currently, the standard of care for most patients with tumors in the lower rectum is total mesorectal excision (TME), which involves removing the affected rectum, surrounding fat, and lymph nodes. This intensive surgery often requires patients to have a permanent ostomy bag afterward. Only patients with early-stage T1 rectal cancer are typically eligible for local excision.
The Fox Chase approach represents a significant shift toward organ preservation in rectal cancer treatment. Patients who had incomplete responses after chemotherapy were treated at physician discretion, while those who achieved cT0-T2 or N0 status proceeded to full-thickness transanal excision. Patients with negative margins after excision received concurrent radiation therapy followed by surveillance.
Quality of Life Outcomes
An important aspect of the study was its assessment of patient-reported outcomes. The researchers found:
- Mild declines in overall physical health were observed after chemotherapy, but levels returned to baseline at the first follow-up survey
- Bowel function scores remained consistent throughout the study period
- Male sexual function showed no negative effects from the treatment
- Assessment of female sexual function was limited due to incomplete surveys
"Neoadjuvant chemotherapy and local excision allows for organ preservation in node-negative low rectal cancer and met its primary end point," Dr. Buettner stated. "Our approach adds to the mounting evidence for organ preservation and needs further investigation."
Research Team and Future Directions
Vanessa Wookey, MD, Assistant Professor in the Department of Hematology/Oncology at Fox Chase, was the lead author on the study, and Namrata Vijayvergia, MD, Assistant Chief of Gastrointestinal Medical Oncology, was the senior author.
The researchers acknowledge that larger studies with comparison arms are needed to further validate this approach. "Our study asked: Can we get patients to negative margins using neoadjuvant chemotherapy? The answer, so far, is yes," Dr. Buettner said. "Studying more patients and also having a comparison between patients who get total mesorectal excision versus local excision will be the next step in getting more robust data to help clinicians and patients make informed treatment decisions."
This study builds upon previous research, including the phase 2 OPRA trial, which included patients with node-negative disease. Additional ongoing trials are further investigating organ preservation approaches in node-negative rectal cancer.
For eligible patients with node-negative low rectal cancer, this organ-preserving strategy could represent a significant advancement in treatment options, potentially improving quality of life while maintaining oncologic outcomes.
