Local Excision After Chemo Achieves Negative Margins in Rectal Cancer

A phase 2 trial presented at SSO met its primary end point by achieving negative margins in 79% of patients with node-negative rectal cancer.

Neoadjuvant chemotherapy and local excision allowed for organ preservation in a small cohort of those with node-negative low rectal cancer, resulting in margin negative local excisions in over 75% of patients with no decline in mental health or bowel function, according to results from a phase 2 trial (NCT03548961) presented in a press briefing at the 2025 Society of Surgical Oncology Annual Meeting.¹

Results demonstrated that 84% (n = 16/19) of patients underwent local excision, and negative margins were achieved in 79% of patients (n = 15/19); 53% (n = 10/19) of patients were downstaged. Pathologic complete responses (pCRs) were achieved in 31% of patients (n = 5/19). At the median follow-up of 26 months, no local recurrences were observed.

Mild declines in overall physical health were observed after chemotherapy, but levels returned to baseline at time of first follow-up survey per PROMIS global health scores; data from 16 patients were used for baseline, data from 12 patients were used prior to local excision, and data from 9 patients were used at follow-up.

Regarding FACIT-D scores, both FACIT-D and the diarrhea subscale were consistent all throughout the study period, with FACIT-D dropping subtly prior to local excision then rebounding at follow-up. Male sexual function scores, per the International Index of Erectile Dysfunction (IIEF), did not show any negative effect from study treatment. Female sexual function assessment 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,” presenting author Hannah Buettner, MD, a Complex General Surgical Oncology fellow at Fox Chase Cancer Center, stated in the presentation.¹ “Our approach adds to the mounting evidence for [organ preservation] and needs further investigation.”

The trial enrolled a total of 19 patients who received up to 6 cycles of leucovorin plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy followed by MRI pelvis flex sigmoidoscopy; if a patient had an incomplete response, future treatment was left to physician discretion, and if a patient had cT0-T2 or N0 status, they proceeded to full thickness transanal excision. If patients had positive margins after excision, they proceeded to treatment of physician’s discretion, and if they achieved negative margins, patients proceeded to concurrent radiation therapy then surveillance.

Eligible patients were 18 years or older with histologically proven adenocarcinoma of the lower rectum with clinical stage T1-T3; those who had N0 disease with high risk T1 and low risk T3 were allowed to enroll.² Additional eligibility criteria included an ECOG performance status of 0 or 1, no prior therapy for rectal cancer, normal organ and marrow function, and the ability and willingness to sign a written informed consent document.

Those who had contraindications to FOLFOX chemotherapy and pelvic radiation, receipt of other investigational agents, chemotherapy for other malignancies within 3 years of enrollment, any prior pelvic radiation, uncontrolled intercurrent illness, any prior malignancies that required systemic therapy within the past 3 years, and a history of allergic reactions to agents similar to those used in this study were not permitted to participate in the trial.

The trial’s primary end point was the proportion of patients with negative margins after local excision following neoadjuvant chemotherapy. Additional end points included PROMIS global health score, FACIT-D score, IIEF score, and female sexual function index score.

The study authors noted that in the phase 2 OPRA trial (NCT02008656), 29% of patients had node-negative disease, and 13% had clinical stage T4; the median distance from anal verge was 4.5 cm, and 44% had surgical resection, of which 94% had total mesorectal excision.

Additional, ongoing trials are further investigating organ preservation in node-negative rectal cancer (NCT03259035).

References

1. Wookey V, Buettner H, Farma J, et al. Phase II study of organ preservation using neoadjuvant chemotherapy and local excision in node-negative low rectal cancer. Presented at the 2025 Society of Surgical Oncology Annual Meeting; March 27-29, 2025; Tampa, FL.
2. Organ preservation in early rectal cancer patients. ClinicalTrials.gov. Updated April 2, 2024. Accessed March 27, 2025. https://tinyurl.com/4p7k3wfy