PHOENIX – The standard sequential approach to treatment of patients with isolated synchronous liver metastases of colorectal cancer, entailing up-front removal of the primary tumor, is associated with growth of the metastases, according to results from a retrospective cohort study.
A team led by Dr. Alistair Slesser, a surgical registrar at the Royal Marsden Hospital in London, studied 114 patients with colorectal cancer who had synchronous liver metastases, meaning ones identified within a year of the cancer diagnosis, and no other metastases.
Results showed that patients whose initial treatment was resection of the colorectal primary tumor had ninefold higher odds of progression of their liver metastases at 3 months, compared with patients whose initial treatment was chemotherapy, he reported at the annual meeting of the American Society of Colon and Rectal Surgeons.
Although liver metastases showed regression during 3-6 months of treatment in both groups, the rate was somewhat slower in the primary tumor resection group.
"Our findings suggest that an up-front primary tumor resection is actually an adverse prognostic factor. Indeed, our results have demonstrated that up-front primary tumor resection seemed to negate the effects of the adjuvant therapy on the treatment of the liver metastasis," Dr. Slesser commented.
"How does this apply clinically? We would recommend that patients who have limited metastatic disease, instead of having an up-front primary tumor resection perhaps [they should] be treated with neoadjuvant chemotherapy first. Or perhaps another surgical approach, like a simultaneous resection, should be considered to negate the adverse effects of a primary tumor resection on the metastatic disease," he said.
"When patients have lesions which are suspicious for liver metastases, we would recommend that these patients [be] thoroughly investigated, and if metastatic disease is confirmed, then again, we would recommend that they have chemotherapy prior to any subsequent intervention," he added.
The mechanism leading to growth of liver metastases after primary tumor resection is unknown, according to Dr. Slesser. "There is possibly an association for ... biological reasons. The other reason is that perhaps when a patient has an up-front primary tumor resection, there is a delay in getting chemotherapy, and that can cause the progression that we see."
Session attendee Dr. Gary Dunn, of the University of Oklahoma, Oklahoma City, asked how much time elapsed between up-front resection and receipt of adjuvant chemotherapy in that group, and the variance in this measure, noting, "That will significantly affect your outcome, if some patients started at 6 weeks and some patients started at 12 weeks postop."
"Usually, patients waited 6 weeks before they started chemotherapy postoperatively," Dr. Slesser explained. "The majority of patients who had primary tumor resection had the adjuvant chemotherapy after the postoperative scan; the 3-month scan tends to be the postoperative scan."
Dr. Dunn further wondered about the comparability between groups of the chemotherapy received, asking what agents were used.
"At the Royal Marsden, the chemotherapy regimes tend to be quite uniform," Dr. Slesser replied. "Generally, all patients are on capecitabine [Xeloda] and oxaliplatin, with a monoclonal agent such as bevacizumab [Avastin]. They tend to get that when they have neoadjuvant chemotherapy."
Another attendee said, "Excellent paper, very well presented data, particularly considering there are a lot of retrospective series out there that are showing the up-front resection as a favorable prognostic indicator, which I don’t believe. ... But I would like to see a little more information about how the patients were treated subsequently. Were these patients who they were planning to get to surgery for resection, or were these patients who were treated for palliative intent? Did they have symptomatic primaries?"
"In the majority of these patients, the intent was curative surgery," Dr. Slesser replied. "We tried to exclude patients who were clearly referred for palliative treatment because we really wanted to assess patients who were referred for curative treatment."
Dr. David Shibata
Attendee Dr. David Shibata, of the Moffitt Cancer Center in Tampa, commented, "I think a critical question is that you have done a primary tumor resection and the liver tumor has tended to grow, which is not entirely surprising, but then in those cases, how many became unresectable from a liver standpoint?"
"About 60% ended up having hepatectomies," Dr. Slesser said, noting that the data reported looked only at the short-term time frame. "We do have further results, which will be in the paper, pertaining to survival. But the real aim of this study was to look at initial radiological progression of disease, because we thought that the primary tumor resection may be associated with a sudden increase in the size of metastasis."