Liver-first Approach to Colorectal Cancer with Synchronous Hepatic Metastases

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“The liver-first approach for patients with colorectal cancer with synchronous liver metastases is possible but is associated with a wide range of survival outcomes, despite protocol similarities between studies,” according to a review of four cohort studies identified by a literature search.

“All liver-first protocols administered neoadjuvant chemotherapy as the first intervention, using conventional oxaliplatin-based or irinotecan hydrochloride–based chemotherapy regimens augmented by biological agents, such as bevacizumab [Avastin], from the time of availability of these latter agents,” the researchers reported. “Liver resection was the first operative step (and the second intervention). Chemoradiotherapy was administered after liver resection in those patients with rectal primary tumors. Two protocols provided further adjuvant oxaliplatin- or irinotecan-based chemotherapy after resection of the primary tumor. Two protocols addressed the phenomenon of patients with a primary tumor that resolved after adjuvant chemotherapy by the adoption of a watch and wait policy.”

Study Data

The total number of patients in all four studies analyzed was 121, with 90 patients (74%) completing the full protocol and 23 patients (19%) experiencing disease progression during the protocol period. “Among the studies providing data on the hepatic burden of metastases, all report multiple lesions, with a majority of patients having bilobar disease,” the researchers noted. A total of 73 patients (60%) of the original 121 patients developed either progressive or recurrent disease.

“A theoretical disadvantage of the liver-first approach is the delay to chemoradiotherapy for rectal tumors. Despite this, 91 of the 121 patients (75%) in the starting cohort underwent colorectal cancer resection,” the researchers stated. “A potential advantage of the liver-first approach,” they continued, “is that a small number of patients (4 of 121) had a complete response to treatment, with resolution of the primary tumor, and thus did not require colorectal resection. This option for observation is clearly not available with the classic approach.”

In an accompanying editorial, Andrew Klein, MD, MBA, of Cedars-Sinai Medical Center in Los Angeles stated that the investigators “correctly recognized that, among these 4 cohorts of patients, the heterogeneity of survival rates, which varied from 31% to 90%, precluded meaningful group analysis.”

Dr. Klein also challenged the researchers’ conclusion that their analysis supports the need for a clinical trial comparing liver-first vs bowel-first approaches. “The pivotal factor limiting improvement in patient outcomes appears to be responsiveness to chemotherapy,” he stated. “Controlling progression of tumor growth during the protocol period …, as well as converting unresectable hepatic lesions to resectable, will be predicated on the development of increasingly effective chemotherapeutic agents, not the timing of surgical extirpation.” ■

Jegatheeswaran S, et al: JAMA Surg 148:385-391, 2013.

Klein A: JAMA Surg 148:392, 2013.