Postchemo Disappearance of Liver Mets Doesn't Mean Cure

ATLANTA—Chemotherapy may render some liver metastases of colorectal cancer no longer visible by preoperative CT and ultrasound imaging (see also article on page 21), but viable cancer cells are still present in about four in five of these sites. This was the key finding of a study presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (abstract 3501).

"Most patients with colorectal liver metastases receive systemic chemotherapy if the metastases are unresectable or before surgery, and the tumor response to chemotherapy is assessed on imaging with CT scans," said Bernard Nordlinger, MD, of the Hpital Ambroise Par, Boulogne, France. "Complete response on imaging is defined as the disappearance of target lesions and is considered the best indicator of the efficacy of chemotherapy, but the significance of complete response of liver metastases on imaging after chemotherapy is not certain."

Dr. Nordlinger and his colleagues conducted a study to assess the correlation between complete response on imaging and complete pathologic response, and to determine if liver metastases that disappear on imaging after chemotherapy can be considered as cured. Searching the records of 586 consecutive patients treated for liver metastases of colorectal cancer at their institution between 1998 and 2004, the investigators identified 38 who met study inclusion criteria (presence of up to 10 liver metastases before treatment, and disappearance on CT and ultrasound imaging of at least one liver metastasis after chemotherapy).

The patients underwent triple-phase helical CT scanning combined with ultrasound before starting chemotherapy and after every three to four cycles. Three criteria were required to document disappearance of liver metastases: no more visible lesion at the initial site, no ring enhancement, and no calcification.

At the time of surgery, surgeons carefully inspected and palpated the liver, and performed intraoperative ultrasound at each of the initial sites of liver metastases. The preoperative finding of disappearance was confirmed if no lesion and no calcification were identified. For liver metastases that had been judged as initially resectable before their disappearance, surgeons resected the site. For initially unresectable bilobar metastases that became resectable after disappearance of some metastases, surgeons re-sected visible metastases and left the sites that had disappeared in place.

All resected specimens were examined pathologically, with special attention to the sites of metastases. After surgery, patients continued the chemotherapy regimen given preoperatively and underwent clinical, CT, and ultrasound examination every 4 months for 2 years and then every 6 months thereafter, he said.

Study Findings

Preoperative chemotherapy was associated with the disappearance on CT and ultrasound images of 66 liver metastases in the 38 patients. The maximal initial diameter of the metastases was 20 mm, on average, and all of the metastases that disappeared measured less than 45 mm.

Of the 66 metastases that had disappeared on imaging:

• 20 were still macroscopically identifiable in the liver at the time of surgery and were resected, both resected and ablated, or left in place; all of these had viable tumor cells.

• 15 were not identifiable at surgery, but the site was resected and was identifiable microscopically in the resected specimen; 12 of these had viable tumor cells.

• 31 were not identifiable at surgery, and the site was left in place; 23 of these were associated with a recurrence at the same site within a year.

Therefore, 55 (83%) of the 66 metastases that had disappeared on preoperative imaging had in fact not been cured. "Complete response by CT scan in patients who have received chemotherapy for colorectal liver metastases does not mean cure in most patients," Dr. Nordlinger concluded.