Surgical resection has long been the bedrock approach to treat and extend the survival of FLC patients. As the Guideline recommends:
“Because FLC is only somewhat responsive to systemic therapies, surgery plays a critical role in treatment. Therefore, aggressive surgical approaches, including multiple debulking surgeries or extreme resections, may be warranted.”
An initial assessment that a patient is not a good surgical candidate should be tempered by the strong evidence that in FLC, unlike many other cancers, “Enabling surgery in patients initially considered unresectable is associated with superior outcomes.” Such data leads knowledgeable surgeons to offer surgery to many patients with advanced FLC. In particular, whereas for some cancers the presence of metastatic disease rules out initial surgery, many FLC patients with known metastases at the time of diagnosis undergo resection and/or liver transplantation.
Furthermore, repeated surgery to treat recurrent disease in the liver and to remove new metastases both are common in FLC. Studies indicate that these procedures can extend survival for some years, with occasional reports of resection of recurrent disease being “curative,” or at least followed by many disease-free years.
Several factors may account for the prevalent use and qualified success of aggressive surgery in FLC, compared to many other cancers:
- The young age of FLC patients and their generally robust health prior to diagnosis
- Tee absence of underlying liver disease (unlike HCC)
- The relatively slow progression and genetic stability of many FLC tumors
- The usefulness of debulking to manage hyperammonemic encephalopathy (brain dysfunction caused by too much ammonia in the blood)
The same factors led to the Guideline recommendation that “Patients with FLC should be considered for liver transplant if they have unresectable disease confined to the liver,” regardless of whether they meet the strict “Milan criteria” for patients with liver cancer to receive a cadaveric liver via the Organ Procurement and Transplantation Network (OPTN). Those who are not eligible for a liver through OPTN must find a willing living donor. Fortunately, liver transplantation requires only blood type matching, which is much less restrictive than the matching for HLA transplantation antigens that is required for other organs.
Aggressive pre-operative procedures and non-transplant resections are likewise endorsed by the Guideline. This includes use of neoadjuvant chemotherapy and locoregional therapy to shrink the total tumor or areas impinging on critical blood vessels, thereby facilitating resection of the tumor. It also encompasses staged resection procedures (sequential surgeries), which take advantage of the ability of healthy liver tissue to regenerate rapidly. This allows a patient to have more extensive surgery without ever falling below the total liver functional capacity required to sustain life.
The Guideline also recommends that, “Even when complete resection is not possible, patients with FLC may be considered for debulking surgery.” Altogether, it is not unusual for a patient to have a double-digit number of surgical procedures, spread over many years.
However, despite the emphasis on surgery’s key role in FLC treatment, the Guideline also recognizes that, in the long run, resection is rarely curative. Recurrence has been reported as late as 18 years after apparently complete removal of a primary liver tumor. Even when not evident from preoperative imaging, spread of the cancer to local lymph nodes is common, and can presage systemic metastatic disease.