HISTOLOGY AND PATTERN OF COLORECTAL CANCER METASTASES

NEW YORK (Reuters Health) - The histological subtype of a colorectal cancer strongly influences its metastatic pattern, researchers from The Netherlands report.

"The differences in metastatic patterns substantiate the importance of taking histological subtype into account during multidisciplinary board meetings, preoperative examination, and follow-up and highlight this variable as a stratification factor in future research initiatives on advanced disease," Dr. Niek Hugen from Radboud University Medical Center, Nijmegen, The Netherlands told Reuters Health by email.

About 20% of patients with colorectal cancer have metastatic disease at the time of presentation.

Previous papers have suggested that there are differences in metastatic patterns between mucinous adenocarcinoma (MC), adenocarcinoma (AC), and signet-ring cell carcinoma (SRCC).

Dr. Hugen and colleagues used autopsy results from 1679 patients with metastatic colorectal cancer and data from 88 patients from the Total Mesorectal Excision (TME) trial who had synchronous metastases to evaluate the patterns of metastases of the three histological subtypes.

Most MC (58.6%) and SRCC (70.7%) patients had metastases at multiple sites, compared with 49.9% of AC patients, according to the authors' report online February 6th in Annals of Oncology.

Liver metastases were present in 73.0% of AC patients and 52.2% of MC patients, compared with only 31.7% of SRCC patients.

Peritoneal metastases affected 48.2% of MC patients and 51.2% of SRCC patients, but only 20.1% of AC patients.

Lung metastases occurred in a third of all cases, with no significant differences among the subtypes.

Far more SRCC patients had metastases to distant lymph nodes (43.9%) compared to patients with MC (22.3%) or AC (19.9%).

Rare metastatic locations (heart, bone, and pancreas) were up to three times more common in SRCC than in MC or AC, the researchers note.

Results from patients in the TME trial were comparable to findings from the autopsy study.

"Knowledge of differences in metastatic patterns is important and may induce changes in clinical practice," Dr. Hugen said. "We found a high rate of peritoneal metastases in MC and SRCC patients, which should raise concern in case of tumor spillage during surgery. It has been advocated that MC patients should undergo resection of the tumor accompanied by perioperative intraperitoneal chemotherapy to improve survival."

"Moreover, our findings may also impact the design of follow-up," Dr. Hugen said. "Since liver and lung metastases are most common, regular imaging of chest and liver should be maintained. However, in case of unusual or indefinable lesions, other imaging techniques, such as PET-CT, should be employed at an earlier stage in MC and SRCC patients. Early detection of peritoneal metastases should be priority in these patient groups. It is debatable how the latter can be achieved, but a laparoscopic second-look procedure could be one of the possibilities that should be explored."

"The debate regarding the prognostic impact of MC has been ongoing," Dr. Hugen added. "Previously we have demonstrated that MC patients seem to have an equal benefit from adjuvant chemotherapy as AC patients. Conversely, we found that in advanced stage disease, MC patients have a poorer response to palliative chemotherapy, resulting in a worse survival. We think that the distinct metastatic pattern of MC may be one of the reasons for this difference in outcome."

"The findings were already known from daily clinical practice but not yet proven in a large patient cohort," Dr. Alexander Stein from Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany told Reuters Health by email. "This analysis did not check any intervention based on these findings, so we could only take prognostic information but nothing to predict our management."

"I think that these findings as they confirm previous smaller studies should help us individualize treatment strategies better with pathology and site of origin in mind," Dr. Tanios Bekaii-Saab from The Ohio State University in Columbus told Reuters Health. "Additionally, these findings may help change the paradigm for follow up of patients after curative resection."

"Pathology and site of origin matter when it comes to prognosis," Dr. Bekaii-Saab said. "Patients with SC and MC are likely to do worse given their predominantly peritoneal pattern of spread."

SOURCE: http://bit.ly/1g1ktJ5

Ann Oncol 2014.