Recurrent Metastatic Colorectal Cancer

Tanios Bekaii-Saab, MD, FACP:This patient did well and continued to follow-up routinely with his oncologist and surgeon with scans and blood tests, including CEA levels. And he continued to feel well except he kept on complaining of some fatigue in the area. Now comes April 2015, where the patient shows up to his medical oncologist’s office and gets through a routine evaluation. His CA was starting to get elevated. That certainly got the oncologist concerned, so the oncologist sends the patient to first get a scan, which showed suspicious lesions in the liver. And then, that was followed by a PET CT scan, which essentially suggested that there was, indeed, disease recurrence with PET-avid lesions in the liver and multiple lobes of the liver, multiple small lesions. Thankfully, there was no cancer anywhere else, so the liver was the only area that lit up on the PET scan suggesting that this is now metastatic recurrent disease.

The oncologist, along with the surgeon, decided that a biopsy would confirm that this is indeed cancer originating from the colon, coming back in the liver. And so, a biopsy was performed, which essentially confirmed that this is adenocarcinoma consistent with colon primary, confirming that his cancer is, indeed, back and in the liver. So, the patient at that time was started on infusional 5-FU with oxaliplatin—what we call FOLFOX—along with bevacizumab. Unfortunately, the patient did not have mutation testing for his tumor. I think, today, it’s critical that all patients who get diagnosed with stage 4 colon cancer have mutation testing from the get-go. It helps with essentially planning the whole treatment of the patient, and it will help us make decisions sometimes for some patients in the first-line setting. At least what needs to happen is allRASmutations, aBRAFmutation, and MSI testing.

And why is it important? So,RASmutations tell us whether there’s a mutation in RAS that would adamantly be a patient who would never be eligible for an EGFR inhibitor, like cetuximab or panitumumab. That’s important to keep in mind. It also tells us a little bit about the overall prognosis. Those that haveRASmutations tend to do a little worse. Now in the presence of known mutation, patients would be eligible at some point for EGFR inhibitors, and we’ll have that discussion. But also, we have to test those patients for aBRAFmutation. And BRAF is also prognostic, but also could alter how we’ll treat those patients. For example, if the patient had aRASwild-typeBRAF-mutated tumor, rather than treating those patients with a FOLFOX/bevacizumab regimen—this is where we have data that would suggest FOLFOXIRI plus bevacizumab—this is a young patient where a more aggressive triplet regimen plus bevacizumab is likely to make a bigger difference than FOLFOX plus bevacizumab. So, it would be, I think, important to do that.

Now comes the MSI testing. It’s mandatory, I think, and it’s now in the NCCN guidelines and other guidelines. In our institution, we do, across the board for all stages from 1 to 4, MSI testing. And it’s important for multiple reasons. If it’s high, especially with a patient with a family history, it may give us a hint that this cancer is driven by the genetics of the patient. And that has implications not just for the patient, but also for the family of the patient—earlier screenings, etc. So, I think it’s important to at least do those tests.

Now there’s also an argument in some institutions, especially large institutions like ours, that we should do a more expanded testing beyond just RAS, RAF, and MSI. Look at HER2, look at FGFR, look at a number of different targets. That’s because in institutions like ours, we also have many of different trials that have different target therapies. I wouldn’t recommend it across the board, frankly, at this point of time in the absence of clinical trials that would be available to patients. But in institutions like ours and larger institutions as well, I think it would make sense to expand it even beyond the minimum required, which right now would be RAS, BRAF, and MSI for all patients. I think that has to be obtained before any treatment decisions have to be made.

Transcript edited for clarity.

November 2012

• A 51-year-old man was referred to gastroenterology for screening colonoscopy.
• Family history includes pancreatic cancer on his father’s side and pre-menopausal breast cancer in his aunt.
• Colonoscopy revealed a 3-cm mass, proximal to the hepatic flexure.
• Biopsy confirmed the lesion to be of adenocarcinoma histology.
• At the time, the patient underwent right hemicolectomy revealing a moderately differentiated tumor. Fifteen lymph nodes were removed and tested negative for metastatic disease, denoting stage T3N0M0 colon cancer.
• The patient healed without complications and received no further treatment.

April 2015

• The patient continued to feel well, except for occasional fatigue and diarrhea.
• Routine evaluation showed elevated carcinoembryonic antigen.
• PET/CT scan revealed several small lesions in multiple lobes of the liver that were PET avid
• Biopsy was performed and confirmed the liver lesions to be metastases from colon cancer
• The patient was referred to a local oncologist and started on infusional 5-FU and oxaliplatin (FOLFOX) in combination with bevacizumab.
• CT scan 2 months after starting treatment showed a partial response to therapy; at 4 months the patients tumor continued to shrink
• Oxaliplatin was discontinued; subsequently the patient received maintenance therapy with capecitabine and bevacizumab, resulting in continued disease control

February 27, 2017

• The patient has had stable disease for 22 months and remains on bevacizumab maintenance therapy.
• He appears generally well and free of symptoms.