Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer

Hermunen, Kethe; Soveri, Leena‐Maija; Boisen, Mogens K.; Mustonen, Harri; Dehlendorff, Christian; Haglund, Caj; Johansen, Julia S.; Österlund, Pia

doi:10.1080/0284186x.2020.1800086

Cited by 33 publications

(39 citation statements)

References 42 publications

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“…Several studies have investigated the prognostic importance of CEA and other biomarkers in the pre-and/or postoperative setting of radically resected CRC [7][8][9][10][11]20,39,40]. Interestingly, very few biomarker studies have investigated the post-adjuvant time point [17,18], which is one of the most important in ctDNA research [36,41].…”

Section: Discussionmentioning

confidence: 99%

“…Many researchers have adopted a strategy of combining multiple biomarkers to better identify patients with a high risk of CRC recurrence. Some have used the same biomarkers as in this study [7,45], while some have used additional biomarkers, such as D-dimer, Glasgow prognostic score, CRP, CRP/albumin ratio, and neutrophil-lymphocyte ratio [20], and plasma miRNA levels combined with CEA and CA19-9 [46]. Elevation of biomarkers, e.g., CEA, CA19-9, YKL-40, IL-6, and CRP, postoperatively or in conjunction with metastasectomy for mCRC has been associated with impaired OS [7,45].…”

Section: Discussionmentioning

confidence: 99%

“…Some have used the same biomarkers as in this study [7,45], while some have used additional biomarkers, such as D-dimer, Glasgow prognostic score, CRP, CRP/albumin ratio, and neutrophil-lymphocyte ratio [20], and plasma miRNA levels combined with CEA and CA19-9 [46]. Elevation of biomarkers, e.g., CEA, CA19-9, YKL-40, IL-6, and CRP, postoperatively or in conjunction with metastasectomy for mCRC has been associated with impaired OS [7,45]. In patients with localised CRC with normal CEA, elevated YKL-40 or CRP identified patients with a high risk of relapse [7].…”

Section: Discussionmentioning

confidence: 99%

“…An age-corrected percentile for YKL-40 was calculated according to the formula: percentile = 100/(1 + (YKL-40 −3 ) * (1.062ˆage) * 5000). Cut-off values were according to Hermunen et al [7]; age-corrected YKL-40 level as the 70.7th percentile of normal controls YKL-40; 4.5 pg/mL for IL-6; 10 mg/L for CRP; 5 µg/L for CEA; and 26 kU/L for CA19-9. Continuous log 2 transformed biomarker values were used in time varying analyses, otherwise elevated over cut-off versus normal values were used.…”

Section: Assessment Of Biomarkersmentioning

confidence: 99%

“…Despite technical advances in imaging, no additional survival benefit was observed when concomitant computed tomography (CT) imaging and CEA were used in a prospective randomised follow-up study [6]. The prognostic value of both preoperative and postoperative CEA has been described in several retrospective and post hoc studies [7][8][9][10][11]. However, the best surveillance algorithm for patients resected for stage II and III CRC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer

Lehtomäki

Mustonen

Kellokumpu‐Lehtinen

et al. 2021

Cancers

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In colorectal cancer (CRC), 20–50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II–IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32–11.69); 3.72 (1.99–6.95); 2.58 (1.18–5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64–5.73); 3.41 (1.55–7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38–7.04) and OS, HR 3.20 (1.39–7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0–53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Assessment Of Biomarkersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer

Lehtomäki

Mustonen

Kellokumpu‐Lehtinen

et al. 2021

Cancers

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Association of Inflammatory Biomarkers With Survival Among Patients With Stage III Colon Cancer

et al. 2023

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ImportanceThe association of chronic inflammation with colorectal cancer recurrence and death is not well understood, and data from large well-designed prospective cohorts are limited.ObjectiveTo assess the associations of inflammatory biomarkers with survival among patients with stage III colon cancer.Design, Setting, and ParticipantsThis cohort study was derived from a National Cancer Institute–sponsored adjuvant chemotherapy trial Cancer and Leukemia Group B/Southwest Oncology Group 80702 (CALGB/SWOG 80702) conducted between June 22, 2010, and November 20, 2015, with follow-up ending on August 10, 2020. A total of 1494 patients with plasma samples available for inflammatory biomarker assays were included. Data were analyzed from July 29, 2021, to February 27, 2022.ExposuresPlasma inflammatory biomarkers (interleukin 6 [IL-6], soluble tumor necrosis factor α receptor 2 [sTNF-αR2], and high-sensitivity C-reactive protein [hsCRP]; quintiles) that were assayed 3 to 8 weeks after surgery but before chemotherapy randomization.Main Outcomes and MeasuresThe primary outcome was disease-free survival, defined as time from randomization to colon cancer recurrence or death from any cause. Secondary outcomes were recurrence-free survival and overall survival. Hazard ratios for the associations of inflammatory biomarkers and survival were estimated via Cox proportional hazards regression.ResultsOf 1494 patients (median follow-up, 5.9 years [IQR, 4.7-6.1 years]), the median age was 61.3 years (IQR, 54.0-68.8 years), 828 (55.4%) were male, and 327 recurrences, 244 deaths, and 387 events for disease-free survival were observed. Plasma samples were collected at a median of 6.9 weeks (IQR, 5.6-8.1 weeks) after surgery. The median plasma concentration was 3.8 pg/mL (IQR, 2.3-6.2 pg/mL) for IL-6, 2.9 × 103 pg/mL (IQR, 2.3-3.6 × 103 pg/mL) for sTNF-αR2, and 2.6 mg/L (IQR, 1.2-5.6 mg/L) for hsCRP. Compared with patients in the lowest quintile of inflammation, patients in the highest quintile of inflammation had a significantly increased risk of recurrence or death (adjusted hazard ratios for IL-6: 1.52 [95% CI, 1.07-2.14]; P = .01 for trend; for sTNF-αR2: 1.77 [95% CI, 1.23-2.55]; P &lt; .001 for trend; and for hsCRP: 1.65 [95% CI, 1.17-2.34]; P = .006 for trend). Additionally, a significant interaction was not observed between inflammatory biomarkers and celecoxib intervention for disease-free survival. Similar results were observed for recurrence-free survival and overall survival.Conclusions and RelevanceThis cohort study found that higher inflammation after diagnosis was significantly associated with worse survival outcomes among patients with stage III colon cancer. This finding warrants further investigation to evaluate whether anti-inflammatory interventions may improve colon cancer outcomes.Trial RegistrationClinicalTrials.gov Identifier: NCT01150045

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Prognostic value of the postoperative carcinoembryonic antigen level in colorectal cancer: A meta‐analysis

Liu,

Jiang,

Cui

et al. 2024

World j. surg.

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BackgroundCarcinoembryonic antigen (CEA) is one of the commonly used preoperative biomarkers for colorectal cancer (CRC), but no meta‐analysis has evaluated the findings of all recently published studies to determine whether its postoperative level can serve as a prognostic indicator.MethodsWe conducted a systematic search for eligible literature from the PubMed, EMBASE, and Web of Science databases in October 2023. Studies that investigated the relationship between postoperative serum CEA levels and prognosis in CRC patients were included. Outcome indicators, including overall survival (OS), disease‐free survival (DFS), and progression‐free survival (PFS)/recurrence‐free survival (RFS), were analyzed using a fixed‐effects or random‐effects model. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used as effective values.ResultsThis meta‐analysis included 20 eligible studies involving 10,114 CRC patients from the East Asian and Western countries. A comprehensive analysis revealed that elevated postoperative CEA levels were associated with low OS (HR: 2.92, 95% CI: 2.36–3.62, and p < 0.000), DFS (HR: 2.81, 95% CI: 2.01–3.94, and p < 0.000), and RFS/PFS (HR: 2.52, 95% CI: 1.75–3.62, p < 0.000). A subgroup analysis by region, analysis type, distant metastasis, HR obtain method, sample size, postoperative measurement date, and study design demonstrated that the negative correlation observed between high serum CEA levels after surgery and poor prognosis was not significantly different between the subgroups.ConclusionWhen CEA levels are found to be elevated during postoperative follow‐up, more active intervention measures should be implemented to further improve the patient's survival outcomes.

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Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer

Cited by 33 publications

References 42 publications

Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer

Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer

Association of Inflammatory Biomarkers With Survival Among Patients With Stage III Colon Cancer

Prognostic value of the postoperative carcinoembryonic antigen level in colorectal cancer: A meta‐analysis

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