Patient Follow-Up in Advanced CRC

Marwan G. Fakih, MD:This gentleman is a 57-year-old male with an excellent ECOG performance status of 0, who underwent a screening colonoscopy. The colonoscopy showed a left colonic tumor, which was biopsied and confirmed to be adenocarcinoma. The patient did not have any evidence of metastatic disease on further workup, and underwent a left hemicolectomy. The pathology showed a T3, N2 tumor with 5 out of 20 positive lymph nodes. Positive lymphovascular invasion was noted, no perineural invasion was noted. The tumor was evaluated for KRAS status and was noted to be KRAS mutated. The tumor is also microsatellite stable. The patient was offered adjuvant chemotherapy. He received 12 cycles of adjuvant chemotherapy with FOLFOX administered for the first 10 cycles. The last two cycles were 5-FU and leucovorin without oxaliplatin, secondary to grade 2 neuropathy. The patient was followed by observation and was noted to have disease recurrence. The patient has multiple metastatic lesions in the liver, was offered chemotherapy, and received FOLFIRI plus bevacizumab in the second-line treatment.

What was the risk for recurrence for this particular individual? This patient has high-risk features, a T3 tumor with N2 disease. We typically use different nomograms to evaluate the risk of recurrence for a patient. We know that there are different risk factors for recurrence, which include the number of positive lymph nodes, the grade of the tumor, the depth of invasion, as well as other clinical factors such as presence of obstruction or perforation. In this particular individual, we would have noted that his risk of recurrence without chemotherapy would likely exceed 50% or is about 50% to 55%. Therefore, the standard of care for this patient is to receive adjuvant chemotherapy as he did. The standard of care is oxaliplatin-based chemotherapy with either 5-FU or with capecitabine.

Given the risk for recurrence for this patient, the appropriate follow-up includes surveillance with CEA (carcinoembryonic antigen) tumor markers and with imaging studies. The current NCCN Guidelines are to obtain a CEA assay every 3 to 6 months in the first 2 years, and every 6 months for years 3, 4, and 5. Given the high risk of recurrence for this patient, imaging studies are also indicated. Those would include a CT scan of the chest, abdomen, and pelvis, and this is typically also performed on an every 6- to 12-months basis for 5 years. In our practice, we typically scan every 6 months in the first 2 years. The reason for such is that the highest risk of recurrence is in the first 2 years after surgery. On years 3, 4, and 5, we typically obtain CT scans on a yearly basis.

For stage IV disease, or patients with metastatic colorectal cancer, we obviously have those patients on systemic chemotherapy. It is very important to monitor those patients more closely. In that particular setting, a CT scan is obtained on an every-2-months basis. Now, it is important to note that while tumor markers may be helpful in assessing the likelihood of response, those are not the standard approach to following patients. Those are adjuvant exams or adjuvant tests in addition to CT scans and monitoring patients. In other words, the accuracy of a CEA in assessing response is not 100%. Therefore, a CT scan has to be done every 2 months in those patients, and no more than every 3 months.

Case Scenario 2:

• A 57-year old man presented for routine colonoscopy and was found to have a descending colon moderately differentiated adenocarcinoma. CEA pre-operatively was 6.
• Laparoscopic colectomy with colo-colonic anastomosis was performed. Final pathology showed a T3N2a (stage IIIb) lesion with 5/20 LNs positive. There was lymphovascular but no perineural invasion.
• Mutation testing revealed a KRAS mutation. The tumor was MSS.
• His ECOG performance status was 0.
• Following surgery, he was given adjuvant therapy with FOLFOX for 12 cycles with oxaliplatin help during the last two cycles because of grade 2 neuropathy.
• Six months later, follow-up imaging revealed recurrence and multiple metastatic hepatic lesions.
• The patient was started on FOLFIRI plus bevacizumab.