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Metastatic colorectal cancer: timing and selecting best management options
Both medical oncologists and surgeons should be involved in the decision-making.
A 64-year-old woman without significant past medical history presented in June 2005 with several months of bleeding per rectum and was found to have a cT3N1M0 rectal adenocarcinoma (by transrectal ultrasound), 9 cm from the anus. She was enrolled in a phase-2 trial with neo-adjuvant concurrent radiation and chemotherapy with weekly oxaliplatin (Eloxatin, Sanofi Aventis) and infusional 5-fluorouracil. She received only four weeks of protocol therapy as the course was complicated by grade-3 diarrhea and grade-4 vomiting. She completed the planned preoperative radiation.
The patient underwent total mesorectal excision in October 2005; pathology demonstrated a T3N0 rectal adenocarcinoma. Postoperatively, she received three cycles of 5-FU/LV administered via the Roswell Park regimen as she refused FOLFOX or FOLFIRI.
She continued to do well until February 2007 when her surveillance CT scan of abdomen and pelvis showed a 3 cm mass in the right lobe of the liver. The CEA level went up from her baseline 2 to 34. Subsequently a PET scan demonstrated a hypermetabolic lesion in the right lobe of the liver as well as in the mid transverse colon (See figures 1 & 2).
A colonoscopy also revealed a mass in the mid transverse colon. She had no symptoms of the disease at that time.
How should her case be managed?
A) Chemotherapy with FOLFOX or FOLFIRI + bevacizumab (Avastin, Genentech)
B) FOLFIRI + cetuximab (Erbitux, ImClone)
C) Surgical resection of liver/colon lesions
D) Surgical resection of liver/colon lesions followed by combination chemotherapy
Wajeeha RazaqCASE DISCUSSION
Conventional management of metastatic colorectal cancer has largely been directed at palliation. Patients with untreated metastatic disease have a median survival of less than 10 months and a five-year survival of less than 5%. Chemotherapy using a 5-FU–based treatment regimen was considered the standard treatment but seldom produced long-term survival.
Over the past several years, the options for treating metastatic colon cancer have expanded and outcomes have been dramatically improved. Combinations of newer agents like irinotecan and oxaliplatin with FU — and later on with the addition of bevacizumab in the first-line setting — have improved the median survival of patients with stage IV disease to 24 months, but the five-year outcome is still dismal.
The failure of systemic chemotherapy to provide long-term survival in patients with metastatic disease has provided the basis for surgical resection of isolated pulmonary or hepatic metastases with encouraging five-year survival rates close to 60% in selected patients.
The combined treatment strategy of chemotherapy and surgical resection in metastatic colon cancer has increased the median survival beyond 30 months, a result never achieved before with any of the two modalities alone. There is still no agreement in terms of the best schedule and duration of chemotherapy and whether it should be administered before or after surgical resection of the metastases.
The necessity to control liver metastases in patients with rapidly evolving, technically unresectable disease represents a reasonable indication for neoadjuvant chemotherapy. A trial to assess the merits of preoperative vs. postoperative chemotherapy is in the planning stages by the American College of Surgeons Oncology Group.
Figure 1: Hypermetabolic liver mass.
Figure 2: Hypermetabolic transverse colon mass.Our patient underwent synchronous subtotal colectomy and partial liver resection in April 2007 without any major complications. Synchronous resection of both colon and liver is also debatable as there are many factors that determine whether these two procedures can be carried out simultaneously: expertise of the surgeon, extent of liver disease and fitness of the patient.
In this case, the colon tumor appeared to be a second primary and less likely to be the source of her metastatic disease than her original tumor. The patient recovered well postoperatively and was started on adjuvant FOLFIRI. Bevacizumab administration was delayed until the second cycle to avoid wound complications. Currently she is receiving chemotherapy and her CEA level declined to 2.
Pending the availability of definitive data, a considered opinion regarding management decisions is suggested. This decision should involve the medical oncologist and surgeon as well as the interventional radiologist when needed. The integration of novel effective systemic biochemotherapy and advanced surgical procedures for metastatic colorectal cancer has transformed the approach to this disease. The physician’s concern becomes less the lack of options but more the appropriate timing and selection of the best option at each point in the patient’s care.
Wajeeha Razaq is a third-year hem/onc fellow at St. Luke’s Roosevelt Hospital Center in New York.