REMOVING LIVER METASTASES FIRST SAFE IN COLORECTAL CANCER

NEW YORK (Reuters Health) - Patients with synchronous colorectal liver metastases (sCRLM) who have their liver metastases removed before the primary tumor may do no worse than those who have their primary tumor removed first, according to a new study from the U.K.

"Controversy exists whether to remove the colon or rectal tumor first, to operate on the liver initially, or to have a combined approach," said Dr. Dean Tsarwhas of Northwestern University Feinberg School of Medicine, who was not involved in the study.

"These authors proved that after correcting for prognostic variables, whether removing the liver metastasis first or delaying liver surgery until after the primary colorectal cancer has been removed, the outcome is the same regarding survival or cancer recurrence," he told Reuters Health by email.

For the study, Fenella Welsh, a surgeon at Hampshire Hospitals Foundation Trust in Basingstoke, U.K., and colleagues collected clinical, pathological and follow-up data from consecutive patients undergoing hepatic resection for sCRLM at one medical center between 2004 and 2014.

Of the 582 patients, who were in their sixties and seventies, 98 had their liver resected first and 467 had their primary colorectal tumor resected first (the classic approach). The researchers excluded 17 patients having simultaneous bowel and liver resection.

The median pre-op Basingstoke Predictive Index (BPI) was significantly higher in the liver-first group than in the primary tumor-first group (8.5 vs. 8), the team reports in the British Journal of Surgery, online February 10. Median follow-up was 34 months.

The five-year disease-free survival rate was lower in the liver-first group than in the primary-first group (23% vs. 45.6%; p=0.001), but there was no difference in five-year cancer-specific survival rates (51% vs. 53.8%; p=0.379) or in overall survival (44% vs. 49.6%; p=0.305).

After matching for pre-op BPI, the difference in disease-free survival was no longer significant (37% vs. 41.2%; p=0.083); cancer-specific survival was 51% vs. 53.2% (p=0.616) and overall survival 47% vs. 49.1% (p=0.846).

"In the largest single-center series to date of the liver-first approach to sCRLM and the first study that has attempted to define criteria for this strategy, we have shown that patients are not disadvantaged by a liver-first approach," Welsh told Reuters Health by email.

Dr. Afsaneh Barzi of the Keck School of Medicine at the University of Southern California in Los Angeles raised questions about the study.

"Combination chemotherapy and targeted agents are significant factors in long-term survival and cure rates," she told Reuters Health by email. "Outcomes without knowledge of the details of chemotherapy and colorectal cancer molecular subtypes are difficult to interpret and translate into an actionable message."

"Unfortunately, chemotherapy data such as timing, kind and duration of drugs, response rates, and molecular subtypes are unavailable; and how these patients were followed after surgery, their frequency of scans, carcinoembryonic antigen testing, and physician visits are also not given. Therefore, this study does not clarify which surgical approach is preferred and thus does not have an impact on the current practice patterns," cautioned Dr. Barzi, who was not involved in the research.

Dr. Alan P. Venook, of the University of California San Francisco School of Medicine, noted that in the decade since this study began in 2004, the patterns of care have changed greatly.

"Most patients get chemotherapy before their liver resection, and patients who do poorly don't go forward with liver resection," he told Reuters Health. "Therefore, the patients with liver metastases who get resected have been pre-chosen to have favorable biology."

"Immediately removing the primary cancer is instinctive and appropriate in symptomatic patients, patients with blockage for example. But it does not necessarily have to be the first step, and if other cancer is nearby, you can lose a couple of months of time by taking out the primary," said Dr. Venook, who also was not involved in the study.

Regarding further research, Welch said, "Some doctors advocate randomized controlled trials to determine the optimal surgical approach for patients with sCRLM. We don't believe that is feasible in this heterogeneous group of patients and would instead advocate individualized patient care."

SOURCE: bit.ly/1M8vp9o

Br J Surg 2016.