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Primary Tumor Resection Followed by Systemic Treatment vs Systemic Treatment Alone in Metastatic Colorectal Cancer: 60-Day Mortality


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As reported in JAMA Surgery by van der Kruijssen et al, 60-day post–random assignment mortality results in the Danish/Dutch phase III CAIRO4 trial showed higher rates of mortality in patients with metastatic colorectal cancer who received primary tumor resection plus systemic treatment vs those receiving systemic treatment alone.

As stated by the investigators, “The role of primary tumor resection in synchronous patients with metastatic colorectal cancer who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from primary tumor resection.”

Study Details

The multicenter trial was conducted by the Danish and Dutch Colorectal Cancer Group at sites in Denmark and the Netherlands and included patients with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms. Patients were enrolled between August 2012 and December 2019; a total of 196 patients were randomly assigned to receive primary tumor resection followed by fluoropyrimidine-based chemotherapy with bevacizumab (n = 97) or fluoropyrimidine-based chemotherapy with bevacizumab (n = 99). The primary outcome measure of the current analysis was mortality through 60 days after random assignment.

Patients with metastatic colorectal cancer who were [randomly assigned] to primary tumor resection followed by systemic treatment had a higher 60-day mortality than patients [randomly assigned] to systemic treatment. Especially patients [randomly assigned] to the primary tumor resection arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited.
— van der Kruijssen et al

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Key Findings

Receipt of three or more cycles of systemic therapy within 60 days after random assignment occurred in 6% of patients in the primary tumor resection group and 77% of the systemic treatment group.

In intention-to-treat analysis, death occurred within 60 days from random assignment in 11 patients (11%, 95% confidence interval [CI] = 6%–19%) in the primary tumor resection group vs 3 patients (3%, 95% CI = 1%–9%) in the systemic treatment group (P = .03).

In the primary tumor resection group, two patients died before surgery, due to cerebrovascular injury and euthanasia; five died after primary tumor resection but before start of systemic therapy, four due to rapid disease progression and one due to surgical complications; and four died after primary tumor resection and systemic therapy, two due to toxicity related to systemic treatment, one due to sepsis without neutropenia, and one due to unknown reason. In the systemic treatment group, one patient died due to disease progression, one due to toxicity related to systemic treatment, and one due to colonic perforation before start of systemic treatment.

In per-protocol analysis, death occurred within 60 days in nine patients (10%, 95% CI = 5%–18%) in the primary tumor resection group vs two patients (2%, 95% CI = 1%–7%) in the systemic treatment group (P = .048). Among 90 patients in the primary tumor resection group who underwent resection, 4 (4.4%) died within 30 days after surgery.

In the primary tumor resection group, risk of 60-day mortality was significantly higher in patients with elevated levels of serum lactate dehydrogenase (P = .046), aspartate aminotransferase (P < .001), alanine aminotransferase (P = .002), and neutrophils (P = .04) vs patients with normal levels.

The investigators concluded, “Patients with metastatic colorectal cancer who were [randomly assigned] to primary tumor resection followed by systemic treatment had a higher 60-day mortality than patients [randomly assigned] to systemic treatment. Especially patients [randomly assigned] to the primary tumor resection arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited.”

Miriam Koopman, MD, PhD, of University Medical Center Utrecht, Utrecht University, is the corresponding author for the JAMA Surgery article.

Disclosure: The study was funded by the Dutch Cancer Society and Hoffmann-La Roche Ltd. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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