Surgical and chemotherapeutic advances in CLM resection
Up to 25 percent of patients diagnosed with colorectal cancer (CRC) initially present with liver metastases and up to 50 percent will develop them later in the course of their disease. About 15 percent of these patients are candidates for potentially curative surgical resection.
Fifteen years ago, the outlook was bleaker. The prognosis for metastatic CRC in general was poor, and hepatic resection, if offered at all, was limited to patients with three or four liver metastases. Since then, advances in surgical techniques and chemotherapeutic treatment modalities have helped improve tumor resectability and expanded the group of eligible patients to include those with multiple bilobar lesions and extrahepatic disease.
KMarie Reid Lombardo, M.D., M.S., a hepatobiliary and pancreas surgeon at Mayo Clinic's campus in Rochester, Minnesota, says five-year survival rates for patients with resectable colorectal liver metastases (CLM) now approach 60 percent. "We are almost treating CLM like a chronic disease. It is becoming increasingly common to bring patients back to surgery for recurrences," she says.
Still, the optimal selection of patients for hepatic resection is evolving and criteria for resectability vary among institutions and patients. Standard indications for resectability include the ability to:
- Obtain a complete resection
- Preserve at least two adjacent liver segments with adequate vascular inflow and outflow
- Preserve a liver remnant of at least 20 to 25 percent in a healthy liver
Yet Dr. Reid Lombardo points out: "You can't make blanket recommendations for surgery because treatment depends on presentation, and presentation is very heterogeneous. To assess more challenging surgical cases, we calculate the total liver volume, tumor volume and remnant liver volume against body mass. Although up to 80 percent of the liver can be removed, we prefer a buffer and don't like to take more than 70 percent. For a liver damaged by chemotherapy, we leave 40 percent of liver volume; for cirrhotic livers, the number is even higher."
Limited lung metastases aren't a contraindication for resection when pulmonary metatastectomy follows the primary surgery and hepatic resection. But outcomes are less positive than for liver-limited disease, with a five-year survival rate of approximately 30 percent.
The last decade has seen a rapid increase in novel chemotherapeutic strategies. At Mayo Clinic, most patients who have CLM undergo a preoperative neoadjuvant chemotherapy regimen with FOLFOX (folinic acid, 5-fluorouracil and oxaliplatin) or FOLFIRI (folinic acid, 5-FU and irinotecan).
"For very low-risk patients with easy-to-resect lesions, we may go straight to surgery, but we are leaning more toward upfront chemotherapy to maximize outcomes," Dr. Reid Lombardo explains. "We want to know if patients are going to respond to treatment, which can usually be determined in three or four cycles of FOLFOX. Response to chemotherapy is the best predictor of outcome; if the disease progresses during treatment, then surgery may not be beneficial."
When used to downsize tumors, chemotherapy can also permit the removal of metastases initially considered unresectable. But it doesn't improve disease-free or overall survival in patients with resectable hepatic tumors, according to a Mayo Clinic study published in 2009 in the Journal of Gastrointestinal Surgery.
Furthermore, chemotherapy negatively affects the liver, making it harder to resect and more susceptible to postoperative failure. Reducing liver insufficiency and ensuring adequate liver growth are essential. One approach is to use portal vein embolization (PVE) to induce preoperative hypertrophy in the future liver remnant. Studies have shown a 10 to 25 percent increase in remnant size after PVE. Another method uses radiofrequency ablation and other nonsurgical techniques to decrease tumor size prior to surgical resection. Ablating more-central tumors helps preserve the parenchyma and ensure adequate residual liver volume.
Dr. Reid Lombardo uses a triple-phase contrast CT protocol for preoperative assessment of the tumor load and intraoperative ultrasound to identify smaller lesions the original imaging studies may have missed. She also favors laparoscopic and robotic resections. Advantages of these less aggressive approaches include:
- Smaller incisions
- Less pain
- Decreased length of hospital stay
- Reduced bleeding
- Better wound healing
- Possibly easier repeat resections
- Fewer overall complications
"Laparoscopic liver resection has been available at Mayo Clinic since 2006, and we know the technology is safe and feasible for cancerous indications," she says. "Minimally invasive resection definitely requires a steeper learning curve and an experienced surgical team to ensure vascular control and complete tumor removal, but it has many benefits for patients."
Dr. Reid Lombardo says many patients with CLM are assumed to be unresectable and therefore not referred to highly experienced centers where they potentially could be treated; about 15 to 20 percent of patients eligible for surgical resection don't receive it. Patients referred with livers severely damaged by chemotherapy present other challenges.
"To avoid these problems, patients really need a multidisciplinary approach, where they are seen by hepatobiliary surgeons, gastroenterologists, medical and radiation oncologists, and interventional radiologists," Dr. Reid Lombardo says. "We can perform directed chemotherapy or radiation in the liver to downsize tumors with the hope and goal of surgery afterwards and can tailor chemotherapy based on KRAS mutations. We have an increased understanding of the biology of tumors and of surgical resection and what we can safely offer. And if we can't offer surgery, we can make recommendations for interventional radiation to help manage disease. This level of surgical and medical expertise is available for patients with CLM at all Mayo Clinic campuses."
For more information
Boostrom SY, et al. Impact of neoadjuvant chemotherapy with FOLFOX/FOLFIRI on disease-free and overall survival of patients with colorectal metastases. Journal of Gastrointestinal Surgery. 2009;13:2003.