Interaction Between Primary Tumor Resection, Primary Tumor Location, and Survival in Synchronous Metastatic Colorectal Cancer

Kruijssen, Dave E. W. van der; Brouwer, Nelleke; Kuil, Auke J S van der; Verhoeven, Rob H.A.; Elias, Sjoerd G.; Vink, Geraldine R.; Punt, Cornelis J.A.; Wilt, Johannes H. W. de; Koopman, Miriam

doi:10.1097/coc.0000000000000823

Cited by 11 publications

(4 citation statements)

References 48 publications

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“…Population-based data from the Netherlands and the United States suggest that primary tumor location might have predictive value for the effect of PTR. During the first 3 months after PTR, the mortality rate was demonstrated to be high in patients with right-sided colon cancer compared with patients with left-sided colon cancer who underwent PTR …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…The CAIRO4 trial randomized patients with colorectal cancer and unresectable metastases with no severe signs or symptoms attributable to the primary tumor to systemic treatment alone versus primary tumor resection followed by systemic treatment. 110 Among the 196 patients analyzed, 60-day mortality was increased in the primary tumor versus chemotherapy-alone group (11 vs. 3%). On the basis of these two studies, there does not appear to be a role for routine primary tumor resection among asymptomatic patients with unresectable synchronous metastases.…”

Section: Primary Tumor Management In Unresectable Stage IV Diseasementioning

confidence: 95%

The Ugly: Metastatic Colon Cancer—Surgical Options

Dossa,

Weiser

2024

Clin Colon Rectal Surg

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Over 50% of patients with colorectal cancer develop metastatic disease. Although systemic therapy remains the backbone of palliative treatment, select patients may be candidates for surgical resection with curative intent. Given increasing evidence of the association between metastasectomy and prolonged survival, surgery has acquired an increasingly central role in the management of liver, lung, and peritoneal metastases. This is compounded by accumulating advances in local and systemic treatments that have allowed for expansion of the resectability pool, bringing the potential for curative surgical treatment to increasing numbers of patients with stage IV disease. However, as the boundaries of resectability are pushed, patient selection and consideration of tumor-related and technical factors are imperative to the identification of patients for whom surgery would be of the greatest benefit.

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“…Of these, 48 studies were selected for full-text screening, but only 10 were included in the nal analysis. [1,[7][8][9][12][13][14][15][16][17] The 38 omitted studies were omitted because they enrolled patient prior to 2004 (n = 17) or were not RCTs or RCSs with su cient PSM or IPTW (n = 21). The 10 selected studies in the nal analysis addressed at least one index related to the outcomes.…”

Section: Study Selectionmentioning

confidence: 99%

Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis

Lai

Chern

et al. 2023

Int J Colorectal Dis

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The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. MethodsThe PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. ResultsAfter reviewing 3,626 articles, we identi ed 10 studies including a total of 38,947 patients. OS differed signi cantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identi ed no signi cant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas signi cant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed signi cantly between the treatment arms (risk ratio [RR] 3.47; 95% CI: 1.21-9.96; p = 0.02). ConclusionsIn RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. By contrast, in RCSs, PSM or IPTW provided improved OS. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required.

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Interaction Between Primary Tumor Resection, Primary Tumor Location, and Survival in Synchronous Metastatic Colorectal Cancer

Cited by 11 publications

References 48 publications

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

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

The Ugly: Metastatic Colon Cancer—Surgical Options

Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis

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