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

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Case 26:

Discussant: AXEL GROTHEY, MD

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Case Description:

A 49-year-old man presented with primary cecal cancer with 10 of 37 regional positive lymph nodes and small synchronous bilobar liver lesions. PET/CT identified scattered metastases — six in the right lobe and one in the left lobe. All were deemed resectable. Due to the high-risk nature of his disease, he received FOLFOX and bevacizumab, and after four cycles, a follow-up scan showed progressive disease and he was switched to FOLFIRI and cetuximab. Treatment was well tolerated aside from significant rash. After four cycles CT showed some partial disease response and he was sent for surgery. He underwent resection of both the primary lesion and synchronous metastases. Ultrasound confirmed seven bilobar metastases. Five anatomical wedge resections and a nonanatomic wedge resection of the right liver lobe were performed in addition to RFA to the left liver lobe. Postoperatively he was found to have a K-ras mutant tumor and was thus treated with eight cycles of FOLFIRI and bevacizumab. After his treatment course PET/CT confirmed no evidence of disease and a normalization of tumor markers.

Case Discussion:

This 49-year-old man presented with a synchronous cecal cancer and seven small, scattered hepatic lesions. In addition, a number of regional lymph node metastases were visualized on imaging. It’s not that common that we see these initially on imaging — regional node metastases are usually identified in pathology. So we knew up front that this was a high-risk situation, given the synchronous lesions and number of regional node metastases.

Fortunately, six of the hepatic metastases were in the right lobe, one in the left and they were deemed resectable. However, whenever we see this appearance of small, scattered lesions, we are mindful that we’re probably not seeing all the metastases in the liver. From an oncologic perspective, it made more sense to treat the patient with chemotherapy before going to surgery.

Whether to use preoperative therapy is generally dependent on the presence of high-risk features for relapse. For example, in patients like this with synchronous primary and metastatic disease, I tend to offer neoadjuvant therapy because we don’t know anything about the biology of the tumor. We have only one snapshot in time, unlike a patient who presents with Stage II or III colon cancer and then two or three years later returns with resectable liver metastases. In the later, we know it took years to develop metastases and in those patients I might use only postoperative therapy. Of course, other factors need to be taken into consideration also.

Another scenario, which is quite common, is the patient with Stage III colon cancer who recurs within half a year or a year after adjuvant FOLFOX/chemotherapy. This patient would appear to have disease somewhat resistant to FOLFOX, so preoperative therapy with FOLFIRI establishes whether that is an effective alternative. If they don’t respond, then you spared that patient unnecessary postoperative therapy.

We treated this patient with four cycles of modified FOLFOX-6 and bevacizumab. We then evaluated him and found slight disease progression on imaging and an increase in his CEA level. We had to decide whether to proceed with surgery or try another systemic regimen first. If we went directly to surgery, the question would then be what to use postoperatively. We certainly wouldn’t use FOLFOX since the tumor had progressed on it, but the role of FOLFIRI has not been established in the adjuvant setting. So we needed to establish preoperatively whether it would be effective in this case.

We conferred with the surgeon and discussed the risk of the tumors becoming unresectable if we tried another regimen and they continued to grow. Since the tumors were small, the surgeon felt that even if they doubled, they would still be resectable.

We treated the patient with FOLFIRI and cetuximab. I saw this patient before the ASCO 2008 meeting, so we had no knowledge of the value of K-ras testing at the time. However today, I definitely would have checked the K-ras status of the primary colon tumor or hepatic metastases before treatment. The patient developed a significant rash in response to therapy, but otherwise tolerated it well.

After four cycles, we saw a CEA response and some improvement on the CT scan. The patient went to surgery and ultrasound confirmed that there were only seven lesions. This was reassuring, because we’ve had cases where patients went to surgery with five known lesions, but the resection was aborted because an ultrasound then revealed 30 lesions.

The surgeon performed five anatomical wedge resections and one nonanatomic wedge resection in the right lobe and treated the metastases in the left lobe with RFA. I believe the reason for the wedge resections — rather than a more aggressive approach — was to spare as much of the liver as possible. These lesions were located peripherally, so they were easily identified and wedged out. I believe this was the right approach, because in a high-risk case like this, additional resections might be required in the future and the more liver parenchyma remaining, the better.

As for the reason to treat the lesion in the left lobe with RFA, I can only assume that this was a centrally located lesion that was not easy to resect. All of the liver lesions were tiny — I believe we can reliably ablate lesions that are smaller than 1.5 to 2 centimeters. If the lesion is larger than two centimeters, then we know the overall outcome is much worse.

At the same time as the metastectomy, the patient underwent a right hemicolectomy. Ten out of 37 lymph nodes were positive. Sometimes liver metastases are resected first and then two weeks later, the primary tumor is removed. To perform both on the same day was a surgical call, but as you can see, this was a high-risk scenario.

After surgery, we had enough tissue to perform a K-ras analysis and found the tumor was mutant, so the cetuximab hadn’t worked. Postoperatively, we switched to FOLFIRI with bevacizumab and he received eight cycles. During his last cycle of systemic therapy, PET/CT showed no evidence of disease and his tumor markers had normalized.


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