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Originally published as JCO Early Release 10.1200/JCO.2008.19.6451 on November 3 2008 © 2008 American Society of Clinical Oncology.
Carcinoembryonic Antigen Monitoring in Metastatic Colorectal Cancer: Words of Caution
Roswell Park Cancer Institute, Buffalo, NY To the Editor: In a carcinoembryonic antigen (CEA) kinetic study in patients with metastatic colorectal cancer, Iwanicki-Caron et al1 demonstrate that the CEA slope, using an exponential-regressive curve connecting the semi-logarithmic values of CEA, accurately predicts for chemotherapy response and progression free-survival. A CEA slope greater than + 0.05 predicted progression with a sensitivity of 85.7% and specificity of 85.1%. On another hand, a CEA slope less than 0.2 predicted a response with a sensitivity of 74.5% and a specificity of 84.7%. The authors conclude in their discussion "CEA allows an accurate evaluation of progression, response, and PFS during chemotherapy in patients with metastatic colorectal cancer."1 Before CEA monitoring is endorsed on a wide scale for monitoring patients with metastatic colorectal cancer, one should note several limitations associated with this assay. CEA sensitivity and specificity is not only tumor dependent, but is also dependent on the site of metastases. Indeed, CEA elevation can be lacking in the setting of metastatic colorectal cancer to lungs. Prior studies have suggested that only 15% patients with solitary lung metastases have a CEA elevation.2 Thus, the development of new lung metastases on computed tomography scan without a CEA elevation may be not be uncommon. Given the limited number of patients with isolated lung metastases (8% of the population) on the Iwanicki-Caron study,1 it would be difficult to make recommendations for this patient population. CEA can also be significantly impacted by chemotherapy. Fluorouracil, leucovorin, and oxaliplatin combination (FOLFOX) has been associated with a CEA surge in 10% of patient who experienced a clinical benefit.3-5 This is characterized by an initial CEA elevation despite a favorable antitumor activity. The rise can persist for 2 months before it recedes to a level below the baseline. To our knowledge, CEA surges have not been clearly attributed to rapid tumor lysis as suggested by the authors, but may rather be related to a direct effect of chemotherapy therapy on CEA RNA translation.6,7 Although CEA surge can be seen with other chemotherapy regimens such fluorouracil monotherapy or irinotecan, the incidence is highest in the setting of FOLFOX.3 Only 31% of the population on Iwanicki-Caron's study population received FOLFOX.1 The relevance of CEA slope in this population, especially its specificity in detecting progression, was not described. Even if we are to ignore the specific situations, one may also wonder in this era of improved radiographic monitoring if the sensitivities and specificities achieved, even with the cutoff slopes selected, are adequate for clinical decision making. In other words, are we ready to accept a disease monitoring modality which, at best, has a specificity of 85%? Significant inherent limitations to CEA testing continue to prevent it from being an adequate stand-alone assay for the monitoring of patients with metastatic colorectal cancer. While we agree that CEA monitoring may add some information to radiographic assessments, the standard monitoring of metastatic colorectal cancer should continue to be serial computed tomography scans. Given the clinically significant rates of false positivity and false negativity with CEA slopes, this modality should not be regarded as an acceptable alternative to radiographic imaging. AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. NOTES published online ahead of print at www.jco.org on November 3, 2008 REFERENCES
1. Iwanicki-Caron I, Di Fiore F, Roque I, et al: Usefulness of the serum carcinoembryonic antigen kinetic for chemotherapy monitoring in patients with unresectable metastasis of colorectal cancer. J Clin Oncol 26:3681-3686, 2008 2. Moertel CG, Fleming TR, Macdonald JS, et al: An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. JAMA 270:943-947, 1993 3. Ailawadhi S, Sunga A, Rajput A, et al: Chemotherapy-induced carcinoembryonic antigen surge in patients with metastatic colorectal cancer. Oncology 70:49-53, 2006[CrossRef][Medline] 4. Fakih MG, Padmanabhan A: CEA monitoring in colorectal cancer: What you should know. Oncology (Williston Park) 20:579-587, 2006[Medline] 5. Sørbye H, Dahl O: Carcinoembryonic antigen surge in metastatic colorectal cancer patients responding to oxaliplatin combination chemotherapy: Implications for tumor marker monitoring and guidelines. J Clin Oncol 21:4466-4467, 2003 6. Ohtsukasa S, Okabe S, Yamashita H, et al: Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs. J Cancer Res Clin Oncol 129:719-726, 2003[CrossRef][Medline] 7. Aquino A, Formica V, Prete SP, et al: Drug-induced increase of carcinoembryonic antigen expression in cancer cells. Pharmacol Res 49:383-396, 2004[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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