An educational tool to assist in the management of hepatic metastases in patients with colorectal cancer

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Case 44:

Discussant: RENE ADAM, MD

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Case Description:

A 48-year-old woman presented with asymptomatic primary colon cancer and approximately 20 highly distributed bilobar hepatic metastases. Disease was not found outside of the colon or liver. Preoperatively, she received eight cycles of FOLFOX. She experienced a drop in her CEA level and simultaneous decrease in the size and number of liver lesions. She was referred to a surgeon, who deemed the disease resectable, but she opted to delay surgery for a month due to the Christmas holiday. She reinitiated FOLFOX, but one month follow up revealed disease progression, precluding surgery at that point. She began an intensive second-line chemotherapy and demonstrated a response sufficient to proceed with resection. She underwent a two-stage hepatectomy, including removal of the primary tumor, left lobe lesions and right portal vein embolization (PVE) for the first stage. This was followed by intercurrent chemotherapy and subsequent right hepatectomy during the second stage. Six months postoperatively, she experienced disease recurrence in the left-liver remnant and was successfully treated with radiofrequency ablation (RFA) and further systemic therapy.

Case Discussion:

This 48-year-old woman, a physician, presented with a large tumor in her colon and 32 synchronous liver lesions. The challenge in this type of case is whether to operate on the hepatic lesions or to begin by using chemotherapy for the primary tumor. The optimal approach for this type of clinical scenario is debatable. However, the hepatic lesions were bilateral and, based on the conditions of her prognosis, we opted to begin with chemotherapy. The patient was not symptomatic from her primary tumor ­— she did not have any digestive symptoms.

Not all surgeons will take the same approach when treating a patient who has synchronous colon cancer with highly distributed bilobar metastases. Whereas some surgeons would resect the primary tumor first then begin chemotherapy — thinking that the primary tumor will have been addressed — like-minded surgeons believe that since the primary is asymptomatic and the hepatic metastases are much more life-threatening, it is best to begin by using systemic treatment. If you resect the primary tumor first and the patient experiences a complicated course, the chance to treat the metastases is lost. For that reason, we use systemic chemotherapy first, rather than performing a column resection first.

Because so many hepatic lesions were present, we were not sure if we could remove all the lesions. The decision to resect is partially based on whether the patient responds to chemotherapy. If the patient does not respond to the first choice of chemotherapy, the best option is to switch to another regimen. The priority is to use a systemic treatment because the disease is systemic.

After eight courses of FOLFOX, the patient’s CEA decreased from 450 to 200. Simultaneously, a decrease in the size and number of liver lesions was observed, prompting her evaluation for surgery at the end of the year (November or December of 2005). Although she was advised to undergo surgery right away, she refused stating that she would prefer to wait until after the holidays. Despite starting a new cycle of chemotherapy to prevent disease progression, tumor markers and the tumor size increased at the end of January. Surgery was no longer recommended because the patient developed progressive disease, and it is well known that the results of surgery are not good when disease progression is observed during chemotherapy. The patient was very upset because she felt that surgery was her only hope for a cure. This demonstrates the importance of proper timing of chemotherapy and surgery and also emphasizes what can happen when the medical and surgical oncologists are not working together early on.

We then decided to exchange the chemotherapy. The patient was intensively treated with second-line chemotherapy. Fortunately, she responded to chemotherapy.

Because her disease was bilateral, we performed a two-stage hepatectomy, first removing the left liver lesion and performing the colectomy at the same time. We also preformed a portal embolization to prepare the liver for the second-stage of the surgery — a right hepatectomy. The removal of the left lesions before the right was the only way to remove all of them without risking liver insufficiency. If all of the lesions had been removed at once, the remnant liver would be too small. Too small is defined as less than 30 percent of the total liver parenchyma when the patient has not received intensive chemotherapy. When using intensive chemotherapy, too small is defined as a remnant liver less than 40 percent.

The first postoperative course was uneventful. Instead of 12 lesions, we discovered 20 in the right liver and instead of six lesions in the left liver, she had 12. So, in contrast to the 20 lesions radiologically assessed, 32 liver lesions were removed in the first- and second-stage hepatectomy. We reinitiated the same chemotherapy prior to the second surgery, the right hepatectomy.

Portal vein embolization is used when the future remnant liver appears too small (ie, less than 30 percent of the total parenchyma when the patient has not received intensive chemotherapy or less than 40 percent, when the patient has received intensive chemotherapy). We try to prevent liver insufficiency postoperatively by performing a portal embolization in a way to encourage hypertrophy of the liver that will be left in place. Hypertrophy of the liver occurs quickly. In Europe, we wait about 1 or 1.5 months for the hypertrophy of the remnant liver before giving chemotherapy. We administer systemic therapy, but we wait two or three weeks for hypertrophy to be established because chemotherapy is antiregenerative, so the liver regeneration will be decreased. Afterward, we reinitiate chemotherapy. It is a sort of compromise between not administering chemotherapy too soon and not waiting too long because you want to prevent a new recurrence or progression of the disease.

Six months after surgery, the patient presented with a recurrence in the left remnant liver. The recurrence was treated by radiofrequency combined with chemotherapy. Tumor markers and CT scans — abdominal and chest CT scans — are preformed every four months.

At this time, it had been more than three years after the discovery of the colon tumor with the bilateral metastasis of the liver, and the patient has been treated efficiently. We are now more than three years after the initial diagnosis. My feeling is that if this patient has been treated only with chemotherapy, she probably would have died. Combining chemotherapy with surgery — even in two stages or through combining postoperative chemotherapy with radiofrequency — is the only way to provide the patient with a relatively good survival benefit.


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