An active 42-year-old man reporting a two- to three-year history of intermittent rectal bleeding presents with, anorexia, fatigue and a 10-pound weight loss. Physical exam reveals enlargement of the liver and colonoscopy shows a mass in the sigmoid, consistent with colon cancer. CT demonstrates multiple (8+), large metastases in both lobes of the liver, but no extrahepatic disease. Considering the location and extent of liver involvement, conversion therapy was required. He completed seven cycles of preoperative FOLFOX with cetuximab and subsequent scan showed marked tumor shrinkage. Extended right hepatectomy, wedge resection of segment II and low anterior resection to remove the primary tumor were performed. All margins were tumor free. He received an additional 12 cycles of chemotherapy postoperatively and is now 24 months without evidence of disease.
Case Discussion:
This was an active 42-year-old man who presented with intermittent rectal bleeding for the previous two to three years, a several-month history of progressive anorexia leading to a 10-lb weight loss and progressive fatigue that began to interfere with everyday activities. Upon evaluation, his stool was heme-positive, he had an enlarged liver and laboratory tests showed elevated liver function. Colonoscopy showed a mass in the sigmoid colon, which was determined to be colon cancer. CT showed multiple (8+), large metastases in both lobes of the liver.
In young patients who have primary tumors and extensive liver involvement, a multidisciplinary approach is needed up front to determine whether surgery could lead to a possible cure or not. This allows you to define a plan of care for the patient and then proceed with the plan, rather than having the unfortunate scenario where someone is started on chemotherapy, is never assessed for a resection of the liver metastases, and despite achieving a good response to chemotherapy, disease becomes progressive. The question then becomes if the patient was ever a candidate for resection.
In this patient’s case, his disease was not considered initially resectable because of the size and location of the liver metastases. However, if the metastases were to shrink, disease could be potentially resectable. It would be a fairly complex surgery because of the concern regarding the volume of residual viable liver, and more importantly, some of the larger metastases were near the major vascular structures, so it might not be possible to obtain clear margins.
Because the primary tumor was not obstructing, the feeling was we could watch it. It did not require a stent. If there was a problem, there would be either a stent placement or surgery to deal with the primary tumor. Obviously one of the concerns in this setting, if you administer chemotherapy, is that the patient becomes neutropenic and then needs emergent surgery because of the primary tumor and it can become a life-threatening situation. That was discussed with the patient — one option would be to initially move forward and resect the primary tumor, and then proceed with chemotherapy, but the danger again is that he had these large metastases. Any delay in starting the chemotherapy would make it unlikely that he would ever proceed to surgery to remove the liver metastases. With his liver function tests already elevated, it would make it difficult to administer chemotherapy, if we had to wait four to six weeks.
He was started on a combination of FOLFOX and cetuximab (he was treated before the K-ras data came out). The decision to use cetuximab was based on early evidence that cetuximab was enhancing the activity of chemotherapy.
We chose to use cetuximab instead of bevacizumab because he had some bleeding from his primary tumor. We were also concerned that by using bevacizumab, the risk for a life-threatening episode of gastrointestinal bleeding would be increased.
The patient received seven cycles of FOLFOX and cetuximab and fared reasonably well. He had a moderate rash, but nothing that required any dose modification. He had some mild cytopenias and mild neuropathy, but got through it pretty well. A subsequent scan showed he had marked shrinkage of his tumor.
We then decided to move forward with surgery. He had an extended right hepatectomy and wedge resection of the residual disease in the left lobe, and a low anterior resection to remove the primary tumor. Even though no identifiable tumor was present in the colon, and only one of 20 lymph nodes around that portion of the colon showed any metastatic disease, the concern was that there might still be some microscopic disease. So the surgeons removed the whole right lobe, and then resected the area that had been involved in the left lobe.
After surgery, he completed 12 cycles of the same regimen he received prior to surgery. At this time, he has no evidence of recurrent disease 24 months after surgery, and he is running marathons again.
I believe his chances for a cure are good at this point. If you examine some of the published series, about 70 or 80 percent of recurrences in this situation occur within the first two years. Although there is still a risk for recurrence, the period associated with greatest risk of recurrence has passed.
