Risk-Adapted Neoadjuvant Chemoradiotherapy in Rectal Cancer: Final Report of the OCUM Study

Area of Science:

• Oncology
• Surgical Oncology
• Radiotherapy

Background:

• Rectal cancer treatment often involves neoadjuvant chemoradiotherapy (nCRT) to reduce locoregional recurrence (LR).
• Identifying patients who benefit most from nCRT is crucial for optimizing treatment strategies and minimizing toxicity.
• Risk stratification based on tumor proximity to the mesorectal fascia is a key factor in treatment decisions.

Purpose of the Study:

• To evaluate if neoadjuvant chemoradiotherapy (nCRT) for rectal cancer can be limited to high-risk patients.
• To determine if restricting nCRT to high-risk individuals compromises oncological outcomes.
• To assess the safety and efficacy of upfront surgery versus nCRT followed by surgery based on risk stratification.

Main Methods:

• A prospective multicenter interventional study involving 1,099 rectal cancer patients (cT2-4, any cN, cM0).
• Patients were stratified into low-risk (mesorectal fascia distance >1 mm) and high-risk (distance ≤1 mm and/or specific tumor characteristics) groups.
• Treatment arms included upfront total mesorectal excision (TME) for low-risk and nCRT followed by TME for high-risk patients, with a primary endpoint of 5-year LR rate.

Main Results:

• Of 884 patients treated per protocol, 530 (60%) had upfront surgery and 354 (40%) received nCRT.
• The 5-year LR rates were 2.9% after upfront surgery and 5.7% after nCRT.
• High-risk patients (n=271) showed the worst outcomes, with a 5-year LR rate of 5.9% and distant metastasis rate of 34.5%.

Conclusions:

• Neoadjuvant chemoradiotherapy (nCRT) can be safely omitted in low-risk rectal cancer patients.
• Upfront surgery is a viable option for low-risk rectal cancer patients, achieving favorable oncological outcomes.
• High-risk rectal cancer patients may require intensified neoadjuvant therapy to improve their prognosis.