Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment

Abstract

The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) 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 PTR.OBJECTIVE To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality.DESIGN, SETTING, AND PARTICIPANTS CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible.INTERVENTIONS Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab. MAIN OUTCOMES AND MEASURESThe aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol.RESULTS A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics.CONCLUSIONS AND RELEVANCE Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR 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.

Long-Term Oncological Outcomes After Colorectal Anastomotic Leakage

“… 27 However, this improvement was not demonstrated in recent RCTs. 28 In accordance with previous studies, this study showed that survival worsens if AL occurs in stage IV RC patients. Clinical deterioration and surgical trauma-induced immunosuppression as a result of AL may induce disease progression in patients with metastatic disease.…”

“…Previous studies demonstrated that palliative resection of the primary tumor can improve overall survival in stage IV CRC patients 27. However, this improvement was not demonstrated in recent RCTs 28. In accordance with previous studies, this study showed that survival worsens if AL occurs in stage IV RC patients.…”

American Society of Clinical Oncology 2022 Annual Meeting Highlights for Radiation Oncologists

“…Sixty-day mortality and postoperative complications were not reported. Consistent with Japan Clinical Oncology Group (JCOG) 1007 and CAIRO4, 21 , 22 the authors of the pooled SYNCRONOUS and CCRe-IV study concluded resection of the primary tumor before chemotherapy does not prolong survival in patients with newly diagnosed stage IV colon cancer with synchronous unresectable metastases.…”

Survival for patients with metastatic colon cancer underwent cytoreductive colectomy in the era of rapid development of anticancer drugs: A real-world analysis based on updated population dataset of 2004–2018

“…WBC count and performance status were identified as significant risk factors for early mortality, whereas LDH levels were not found to be associated with early mortality. In a randomized controlled study of primary tumor resection combined with systemic therapy ( van der Kruijssen et al, 2021 ), patients with metastatic colorectal cancer who received systemic therapy after primary tumor resection had significantly higher 60-day mortality than patients who received systemic therapy alone. In the surgical group, factors such as serum lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and neutrophil count were associated with 60-day mortality.…”