What is the best treatment approach for a patient with metastatic rectal carcinoma with liver-only metastasis?

From the Guidelines

The best treatment approach for a patient with metastatic rectal carcinoma with liver-only metastasis typically involves a multidisciplinary strategy combining systemic therapy and local treatments, with the most recent evidence suggesting the use of FOLFOX or FOLFIRI regimens combined with targeted therapy such as bevacizumab or cetuximab/panitumumab (if RAS wild-type) as the initial treatment.

Key Considerations

• The treatment approach should be individualized based on the patient's performance status, extent of disease, and potential for resection of both the primary tumor and liver metastases.
• Systemic chemotherapy with FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin) or FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) regimens is recommended, often combined with targeted therapy such as bevacizumab or cetuximab/panitumumab (if RAS wild-type) 1.
• For FOLFOX, typical dosing includes oxaliplatin 85 mg/m² IV day 1, leucovorin 400 mg/m² IV day 1,5-FU 400 mg/m² IV bolus day 1, then 2400 mg/m² continuous infusion over 46 hours, repeated every 2 weeks.
• After 2-3 months of chemotherapy, patients should be reassessed for surgical resection of both the primary tumor and liver metastases, either simultaneously or sequentially depending on extent of disease.
• For patients with initially unresectable liver metastases who respond to chemotherapy, conversion to resectability should be pursued, with resection carried out 3-4 weeks from the previous administration of chemotherapy alone or chemotherapy-anti-EGFR mAbs, or at least 5 weeks after chemotherapy-bevacizumab 1.
• If surgery isn't feasible, local ablative techniques like radiofrequency ablation, microwave ablation, or stereotactic body radiation therapy may be considered for liver metastases.

Rationale

• The approach combines systemic control of micrometastatic disease with definitive local treatment of visible disease, offering the best chance for long-term survival or even cure in selected patients with liver-limited metastatic disease.
• The most recent evidence from the ESMO clinical practice guideline for diagnosis, treatment, and follow-up of metastatic colorectal cancer recommends the use of FOLFOX or FOLFIRI regimens combined with targeted therapy as the initial treatment 1.
• The guideline also emphasizes the importance of individualizing treatment based on the patient's performance status, extent of disease, and potential for resection of both the primary tumor and liver metastases.

From the FDA Drug Label

The dominant site of disease was extra-abdominal in 56% of patients and was the liver in 38% of patients The addition of bevacizumab improved survival across subgroups defined by age (<65 years, ≥65 years) and sex. The addition of bevacizumab to FOLFOX4 resulted in significantly longer survival as compared to FOLFOX4 alone; median OS was 13.0 months vs. 10.8 months [hazard ratio (HR) 0.75 (95% CI: 0.63,0.89), p-value of 0. 001 stratified log-rank test]

The best treatment approach for a patient with metastatic rectal carcinoma with liver-only metastasis is bevacizumab in combination with chemotherapy, such as FOLFOX4, as it has been shown to improve overall survival compared to chemotherapy alone 2.

• Key points:
  • Bevacizumab has been shown to improve overall survival in patients with metastatic colorectal cancer, including those with liver-only metastasis.
  • The combination of bevacizumab with FOLFOX4 has been shown to result in significantly longer survival compared to FOLFOX4 alone.
  • The treatment approach should be individualized based on patient characteristics, such as age and performance status.

From the Research

Treatment Approaches for Metastatic Rectal Carcinoma with Liver-Only Metastasis

• The "liver-first approach" is a treatment strategy that prioritizes the resection of liver metastases before addressing the primary rectal tumor 3, 4.
• This approach has been shown to be safe and feasible, allowing most patients to undergo curative resections of both metastatic and primary disease 3, 4.
• Neoadjuvant chemotherapy can be used to downsize the liver metastases, making them more amenable to resection 5, 4.
• The use of neoadjuvant chemotherapy alone, without radiation, has been shown to achieve complete pathological response in some patients with stage IV rectal cancer and liver metastases 5.
• A multimodality approach, including surgery, chemotherapy, and radiation, can improve survival outcomes for patients with metastatic rectal carcinoma with liver-only metastasis 6, 7.
• The optimal treatment sequence and timing of therapeutic interventions are still a matter of debate, and a comprehensive multi-disciplinary team approach is necessary to optimize patient management 7.

Key Considerations

• The "liver-first approach" may be considered the preferred treatment schedule for patients with locally advanced rectal cancer and synchronous liver metastases 3.
• Local neoadjuvant treatment after liver resection may result in preoperative downsizing or even complete clinical response of the primary tumor 4.
• The reversed strategy may eliminate the negative oncologic impact of surgical complications after rectal surgery, as the liver metastases have already been addressed 4.