A 48-year-old woman presents with elevated CEA levels and a one-year history of rectal bleeding. Colonoscopy revealed a nonobstructing rectal adenocarcinoma eight centimeters above the anal verge, and subsequent CT revealed multiple synchronous liver metastases, some of which encased the portal vein. She was determined to have unresectable metastatic disease in the liver and, as she was not obstructed, began systemic chemotherapy with FOLFOX and bevacizumab. She had both a dramatic response to the primary lesion, which disappeared endoscopically, and to her hepatic metastases, which were reduced in volume by more than 50 percent and shrunk away from the main portal vein confluence. She proceeded with an extended right hepatectomy without difficulty or complication. Subsequently, she received three lines of FOLFOX and bevacizumab. As there was still an area of scarring in the rectum, she also underwent a low anterior resection for treatment of her primary rectal cancer. She fared well for 18 months, until the development of pulmonary metastases, which were treated with additional regimens of chemotherapy. She survived for nearly four years since initial diagnosis, but ultimately succumbed to her pulmonary metastases.
Case Discussion:
DR CURLEY: This was a 48-year-old woman who presented with elevated CEA levels and a one-year history of rectal bleeding. Colonoscopy revealed a nonobstructing rectal adenocarcinoma eight centimeters above the anal verge, and a subsequent CT scan revealed multiple synchronous liver metastases, some of which encased the portal vein. She was deemed to have unresectable metastatic disease in the liver.
Because she was not obstructed, a decision was made to proceed with systemic chemotherapy, and she began treatment with FOLFOX and bevacizumab. FOLFOX has become our first-line therapy for neoadjuvant therapy. We know that FOLFIRI can cause problems with the liver. If we have a patient that has a slight chance of having a resection, we use an oxaliplatin-based regimen, rather than irinotecan-based one because steatohepatitis has been associated with irinotecan. We do not feel the use of bevacizumab increases the risk of perforation of the colon. We are able to proceed with bevacizumab in these patients without a high risk.
If we feel a patient with synchronous metastatic disease has resectable disease, we use a perioperative approach and administer two to three months of chemotherapy up front — meaning four to six cycles — and then proceed with resection that may include both the colorectal primary tumor and the metastatic disease, if we feel the patient will tolerate that. We may perform staged resections and then finish with the chemotherapy. Our approach is customized based on the patient and what they are able to tolerate.
This patient showed a dramatic response in both her primary lesion, which disappeared endoscopically, and in her hepatic metastases, with a reduction in the volume by more than 50 percent. The lesions shrunk away from the main portal vein confluence.
She still had obvious metastatic disease in the liver, and that area was of greatest concern. An extended right hepatectomy was performed without difficulty or complication, and she subsequently received FOLFOX and bevacizumab for an additional three months after she recovered from her liver resection. Because she had a scarred area in the rectum, she underwent a low anterior resection as a final treatment for her primary rectal cancer. So, in all, she received chemotherapy followed by a liver resection, further chemotherapy and then the surgical treatment of the primary rectal tumor as her final treatment. Interestingly enough, she had some residual islands of adenocarcinoma in the wall of the rectum, and also some lymph nodes that showed probable prior metastatic disease in the mesorectum, evident as pools of mucin in this area.
We wait at least six weeks before surgery after treatment with bevacizumab, whether we are resecting the primary lesion or the metastatic disease. If we’re able to operate, we will essentially administer FOLFOX without the bevacizumab for one dose. Prior to surgery, the patient will have been without bevacizumab for six weeks and other chemotherapy for four weeks.
In general, the approach to resection of the primary tumor in patients who present with synchronous disease depends on the patient’s symptoms. Essentially, if the primary tumor is not obstructing, not bleeding excessively to the point in which you must perform surgically to deal with the primary tumor, our standard practice is to initiate treatment with systemic chemotherapy first. We’ve seen response in metastatic disease and in the primary lesion. This is true even in patients who we feel will not become candidates for surgical treatment of metastatic disease. They may have peritoneal seeding, or they may have multiple pulmonary metastases — multiple liver metastases. A subset of patients will ultimately succumb to their metastatic disease, but have enough of a response in their primary lesion that they never require surgical treatment. The choice of using surgical treatment as the first treatment depends on whether or not they have an obstructing lesion in the colon.
The patient did well for approximately 18 months thereafter but then developed pulmonary metastases that were treated with several additional regimens of chemotherapy. She survived for a total of almost four years after the diagnosis of her primary rectal adenocarcinoma, but ultimately succumbed to her pulmonary metastases.
