What are the treatment options for achieving long-term survival in patients with liver metastasis?

Treatment Options for Long-Term Survival in Patients with Liver Metastases

Surgical resection of liver metastases offers the best chance for long-term survival and potential cure in selected patients with liver metastases, with 5-year survival rates ranging from 30-50% depending on patient selection. 1

Surgical Management

• Surgical resection should be considered for solitary or confined liver metastases, particularly for colorectal liver metastases (CRLM), which have the most favorable outcomes 1
• In patients with normal liver function, up to 70% of liver volume can be removed without risk of post-operative liver failure 1
• Resectability requires assessment by a multidisciplinary team including experienced liver surgeons and radiologists to determine if complete resection with adequate residual liver function is possible 1
• All hepatic metastases should be referred to tertiary centers where large-volume hepatic resections are performed 1

Patient Selection Criteria

• Key factors for surgical candidacy include:
  • Low operative risk 1
  • Feasibility of complete resection 1
  • Absence of uncontrollable extrahepatic disease 1
  • No disease progression under chemotherapy 1
• The number of metastases is less important than the ability to achieve complete resection with adequate functional liver remnant 1

Perioperative Management

• Perioperative combination chemotherapy with FOLFOX improves progression-free survival by 7-8% at 3 years in patients with resectable liver metastases 1
• The standard approach is 3 months (six cycles) of chemotherapy before and 3 months after surgical resection 1
• Oncologists should refer patients with liver metastases to surgeons before starting chemotherapy, as chemotherapy can make well-responsive metastases difficult to locate and can compromise liver quality 1

Conversion Therapy for Initially Unresectable Disease

• Initially unresectable liver metastases can become resectable after downsizing with chemotherapy 1
• For patients with initially unresectable liver metastases, there is a strong correlation between response rate and resection rate 1
• Standard combination chemotherapy regimens (FOLFIRI or FOLFOX) have been reported to facilitate resection in 7-40% of patients with initially unresectable metastases 1
• The addition of targeted agents (bevacizumab or cetuximab) may further improve response rates 1
• Pathological response to chemotherapy is a surrogate for predicting outcome 1

Alternative Local Therapies

• For patients not considered fit for operative intervention, radiofrequency ablation has been shown to be a safe and effective treatment 1
• Portal vein embolization can be used to induce hypertrophy of the remnant liver in patients requiring extensive resections 2
• Two-stage hepatectomy may be considered for extensive bilobar disease 2
• Ablation techniques can be combined with hepatic resection to reduce local recurrence or destroy contralateral tumor deposits 2

Management of Extrahepatic Disease

• Resection of resectable lung metastases offers 25-35% 5-year survival rates in carefully selected patients 1
• Long-term survival has been reported for patients who undergo resection of pulmonary metastases after curative resection of hepatic colorectal metastases 1
• Long-term survival following resection of adrenal and splenic metastases has been documented 1
• Isolated bone metastases that are easily controlled by radiotherapy do not necessarily preclude liver resection 1

Special Considerations for Different Primary Tumors

• Colorectal liver metastases have the most favorable outcomes after resection, with 5-year survival rates of 30-50% 1, 3
• Neuroendocrine tumor liver metastases also have favorable outcomes with 5-year overall survival ranging from 41-100% after resection 1
• For breast cancer liver metastases, liver surgery can be considered as an adjuvant treatment to systemic therapy in selected patients 1
• The treatment approach differs by primary tumor type - for colorectal cancer, surgery has the key role with chemotherapy as adjuvant, while for breast cancer, systemic therapy is primary with surgery as adjuvant 1

Follow-up After Resection

• Unfortunately, 60-75% of patients will experience relapse following resection of hepatic metastases, with the majority occurring in the liver 1
• Despite high recurrence rates, repeat hepatectomy can be considered for recurrent disease 3
• A recent study showed significant long-term survival can be achieved after recurrence in many patients, with a 10-year overall survival rate of 50.4% 1

Pitfalls and Caveats

• Pretreatment with neoadjuvant chemotherapy in patients with initially resectable disease may compromise the patient's chance of cure, as 20% of tumors will progress during chemotherapy 1
• Complete radiological remission of metastases does not mean absence of disease, as microscopic viable tumor cells often remain 1
• Patients who undergo liver resection at low-volume hospitals are at higher risk of postoperative complications and death than those at high-volume hospitals 1
• There is no role for partial palliative resection of metastases 1