Diagnosis of mCRC

John Marshall, MD:This is a pretty typical case of metastatic colon cancer. The patient is 53 years old, probably never had a colonoscopy at this point. He presents to primary care and, ultimately, to a gastroenterologist with some abdominal complaints and rectal bleeding. He gets a colonoscopy, and there’s a finding of a descending mass, a mass in the descending colon. Biopsy is positive for adenocarcinoma and sent off for genetic testing.

In the meantime, he has a CT scan showing, unfortunately, metastatic disease. There’s one big spot in the lung and a bunch of spots in the liver. And that’s very important when we think about resectability and all of that. He’s symptomatic with this abdominal distension. Biopsy comes back, as I said, positive for adenocarcinoma. And genetic testing for RAS shows that there’s aKRASmutation. So, the patient has aKRAS-mutated left-sided colon cancer with metastases in the liver and the lungs, and has a little hypertension.

Mom had breast cancer, but there’s no other real family history of cancer. And the decision was made to go ahead and initiate therapy with chemotherapy. There are a bunch of choices here. I think the physician did what most physicians do in the United States, and that is oxaliplatin and a fluoropyrimidine—in this case, FOLFOX—plus bevacizumab. Primary is still in place, no surgery has happened to remove that primary, but even with the rectal bleeding, that was done. And in this guy’s case, it was a good decision. The cancer responds nicely. There’s a nice regression of the primary and of the other metastatic lesions, and chemotherapy is continued.

So, typically, now with metastatic colon cancer, we say folks are going to live 2 to 3 years. We’re learning more about being able to be more specific because we all know there are some patients who have a very short prognosis and others who have this forever prognosis—they do very, very well over a long period of time. And to date, we have just been treating them and seeing what happens.

A guy who has a really nice initial response like this would be one of those people that I’m thinking is going to be around a while. We now know, for example,BRAF-mutated tumors don’t do so well, they don’t respond as well. I’m more anxious about that person’s prognosis than a person like this. So, 2 to 3, or more, years is what we would tell the patient. At 53 years old, that’s still way too short.

In this case, the patient’s tumor was sent off for molecular testing, and this has been a really rapidly moving space as to what you need and when. And it wasn’t a year ago that we said, “Oh, if they’re metastatic, if they don’t have a high family history, you don’t need MSI.” But that’s completely different now. You must have microsatellite instability testing on every patient with colon cancer, regardless of stage, regardless of age, for 2 reasons: 1, of course, is to screen for the genetics. Is the patient a lynch patient? Do they have HNPCC (hereditary nonpolyposis colorectal cancer)? But honestly, more importantly now, we know that those patients with MSI-high colon cancers respond really well to the immunotherapy drugs, to the checkpoint inhibitors. And already on guidelines, you see MSI-high metastatic colon cancers being recommended checkpoint inhibitors. So, we absolutely want to know, in this guy right from the get-go, the RAS status.

Let’s make this guy, instead ofKRAS, mutatedKRASwild-type. Many doctors are stopping there and not doing any additional RAS testing. But there are another 20% or so of otherRASmutations that are seen. We also know that BRAF is a negative predictor for response to the EGFR therapies. So, what we’re doing is these broad profiles now so that I know everything, so I don’t have to keep up. I just test everything, and I’ll have in the bank what I need for an individual patient. It’s really important to have MSI, and it’s really important to have broad RAS and BRAF testing for every patient with metastatic colon cancer.

Transcript edited for clarity.

February 2013

• A 53-year old Caucasian man presented to his gastroenterologist complaining of rectal bleeding and abdominal tenderness
• PMH includes hypertension, well-controlled on a beta-blocker
• Family history; mother died from breast cancer
• He underwent colonoscopy with biopsy
  • Pathology results confirmed poorly-differentiated adenocarcinoma
  • Genetic testing was positive forKRASexon 2 codon 12 mutation
• CT scan of the abdomen, pelvis, and chest showed multiple liver lesions and a large nodule in the right lower pulmonary lobe.
• Diagnosis: Adenocarcinoma of the colon; staging, T4N0M1
• The patient was started on FOLFOX and bevacizumab, therapy is well-tolerated
• The second follow-up scan showed a marked decrease in volume of the primary tumor, two of the liver lesions, and the lung lesion.

March 2014

• The patient complains of intermittent shortness of breath but continues his normal activities
• Imaging shows slow but steady progression in the plural lesion
• Bevacizumab therapy was continued; the patient was also started on FOLFIRI
• Follow-up imaging shows continued regression of the lung lesion; patient continues to tolerate therapy with management of gastrointestinal distress

February 2017

• The patient complains of abdominal fullness, nausea, and constipation
• He continues to work full-time but feels sluggish
• MRI indicated diffuse metastatic disease in the peritoneum, consistent with carcinomatosis
• The patient was started on regorafenib 80 mg, with a plan to gradually increase to 160 mg if tolerated