A General Cutoff Level Combined With Personalized Dynamic Change of Serum Carcinoembryonic Antigen Can Suggest Timely Use of FDG PET for Early Detection of Recurrent Colorectal Cancer

Huang, Yu‐Chen; Lee, Pei-Ing; Liu, Mei-Ching; Chen, Chien-Chih; Huang, Kuo‐Cheng; Huang, Andrew T.

doi:10.1097/rlu.0000000000000900

“…One was the definition of an “elevated” pCEA level. Because the elevation of preoperative pCEA was associated with the development of tumor stage, the traditional use of a single pCEA cutoff value for prognostic assessment may not be suitable for all CRC patients at other stages [ 11 – 13 ]. Many recent studies suggested the significance of using different cutoff values for prognostic evaluation [ 12 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Preoperative Serum Carcinoembryonic Antigen Varies with Lymph Node Metastasis Status in Colorectal Cancer

Jia

¹

,

Li

²

,

Teng

³

et al. 2021

Journal of Oncology

4

1

0

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Background. Preoperative serum level of carcinoembryonic antigen (pCEA) is generally recognized as a prognostic factor for colorectal cancer (CRC), but the stage-specific role of pCEA in colorectal cancer remains unclear. Objective. We investigated the prognostic significance of pCEA levels in different tumor stages of nonmetastatic CRC patients. Methods. Six hundred and fifteen CRC patients at stage I–III were retrospectively analyzed. All of them received curative tumor resection. The X-tile program was used to generate stage-specific cutoff values of pCEA for all patients and two subpopulations (lymph node-positive or -negative). The prognostic significance of pCEA was assessed using Kaplan–Meier analysis and Cox proportional hazards regression analysis. A nomogram model that combined pCEA score and clinical feature indexes was established and evaluated. Results. Two cutoff values were identified in the study population. At a cutoff value of 4.9 ng/mL, a significantly higher 5-year overall survival (OS) rate (82.16%) was observed in the pCEA-low group (<4.9 ng/mL) compared with 65.52% in the pCEA-high group (≥4.9 ng/mL). Furthermore, at the second cutoff value of 27.2 ng/mL, 5-year OS was found to be only 40.9%. Stratification analysis revealed that preoperative serum level of pCEA was an independent prognostic factor (OR = 1.991, P < 0.01 ) in the subpopulation of lymph node metastasis (stage III) patients, and the relative survival rates in the pCEA-low (≤4.9 ng/mL), pCEA-medium (4.9–27.2 ng/mL), and pCEA-high (≥27.2 ng/mL) groups were 73.4%, 60.5%, and 24.8%, respectively ( P < 0.05 ). However, no such effect was observed in the lymph node nonmetastasis (stage I and II) subgroup. The established nomogram showed acceptable predictive power of the 5-year OS rate (C-index: 0.612) in lymph node-positive CRC patients, with an area under the curve value of 0.772, as assessed by ROC curve analysis. Conclusions. Pretreatment serum CEA levels had different prognostic significance based on the lymph node metastasis status. Among stage III CRC patients, pCEA was an independent prognostic factor. Five-year OS rates could be predicted according to the individual pCEA level at the different cutoff values.

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“…In the FACS trial, recurrences were missed in patients who had experienced a gradual rise in CEA level, and it was suggested previously that this might be avoided by considering the trend in a series of results over time. In the CEAwatch trial, further investigation was based on CEA trend, on the basis of evidence from other studies that it provides better diagnostic yield than a single measurement.…”

Section: Introductionmentioning

confidence: 99%

Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence in the FACS randomized clinical trial

Shinkins

¹

,

Primrose

²

,

Pugh

³

et al. 2018

British Journal of Surgery

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“…A recent report on interpreting CEA trend in order to initiate positron emission tomography scans to detect recurrence is based on very small numbers and does not report a comparable threshold. 36 Interestingly, in the context of our finding that a negative trend had diagnostic value, Ito et al 37 reported that a slow reduction in the CEA level following primary surgical treatment was predictive of recurrence (presumably residual disease) in the early period after primary surgery.…”

Section: -35mentioning

confidence: 72%

What carcinoembryonic antigen level should trigger further investigation during colorectal cancer follow-up? A systematic review and secondary analysis of a randomised controlled trial

Shinkins

¹

,

Nicholson

²

,

James

³

et al. 2017

Health Technol Assess

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Background Following primary surgical and adjuvant treatment for colorectal cancer, many patients are routinely followed up with blood carcinoembryonic antigen (CEA) testing. Objective To determine how the CEA test result should be interpreted to inform the decision to undertake further investigation to detect treatable recurrences. Design Two studies were conducted: (1) a Cochrane review of existing studies describing the diagnostic accuracy of blood CEA testing for detecting colorectal recurrence; and (2) a secondary analysis of data from the two arms of the FACS (Follow-up After Colorectal Surgery) trial in which CEA testing was carried out. Setting and participants The secondary analysis was based on data from 582 patients recruited into the FACS trial between 2003 and 2009 from 39 NHS hospitals in England with access to high-volume services offering surgical treatment of metastatic recurrence and followed up for 5 years. CEA testing was undertaken in general practice. Results In the systematic review we identified 52 studies for meta-analysis, including in aggregate 9717 participants (median study sample size 139, interquartile range 72–247). Pooled sensitivity at the most commonly recommended threshold in national guidelines of 5 µg/l was 71% [95% confidence interval (CI) 64% to 76%] and specificity was 88% (95% CI 84% to 92%). In the secondary analysis of FACS data, the diagnostic accuracy of a single CEA test was less than was suggested by the review [area under the receiver operating characteristic curve (AUC) 0.74, 95% CI 0.68 to 0.80]. At the commonly recommended threshold of 5 µg/l, sensitivity was estimated as 50.0% (95% CI 40.1% to 59.9%) and lead time as about 3 months. About four in 10 patients without a recurrence will have at least one false alarm and six out of 10 tests will be false alarms (some patients will have multiple false alarms, particularly smokers). Making decisions to further investigate based on the trend in serial CEA measurements is better (AUC for positive trend 0.85, 95% CI 0.78 to 0.91), but to maintain approximately 70% sensitivity with 90% specificity it is necessary to increase the frequency of testing in year 1 and to apply a reducing threshold for investigation as measurements accrue. Limitations The reference standards were imperfect and the main analysis was subject to work-up bias and had limited statistical precision and no external validation. Conclusions The results suggest that (1) CEA testing should not be used alone as a triage test; (2) in year 1, testing frequency should be increased (to monthly for 3 months and then every 2 months); (3) the threshold for investigating a single test result should be raised to 10 µg/l; (4) after the second CEA test, decisions to investigate further should be made on the basis of the trend in CEA levels; (5) the optimal threshold for investigating the CEA trend falls over time; and (6) continuing smokers should not be monitored with CEA testing. Further research is needed to explore the operational feasibility of monitoring the trend in CEA levels and to externally validate the proposed thresholds for further investigation. Study registration This study is registered as PROSPERO CRD42015019327 and Current Controlled Trials ISRCTN93652154. Funding The main FACS trial and this substudy were funded by the National Institute for Health Research Health Technology Assessment programme.

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A General Cutoff Level Combined With Personalized Dynamic Change of Serum Carcinoembryonic Antigen Can Suggest Timely Use of FDG PET for Early Detection of Recurrent Colorectal Cancer

Abstract: A posttreatment CEA level rise to greater than 13 ng/mL is suggestive of the optimal use of FDG PET, and so is a mild increase below 13 ng/mL at an increase rate over 3.34.

Cited by 9 publications

References 31 publications

Prognostic Significance of Preoperative Serum Carcinoembryonic Antigen Varies with Lymph Node Metastasis Status in Colorectal Cancer

Prognostic Significance of Preoperative Serum Carcinoembryonic Antigen Varies with Lymph Node Metastasis Status in Colorectal Cancer

Serum carcinoembryonic antigen trends for diagnosing colorectal cancer recurrence in the FACS randomized clinical trial

What carcinoembryonic antigen level should trigger further investigation during colorectal cancer follow-up? A systematic review and secondary analysis of a randomised controlled trial

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