CEA as a blood-based biomarker in anal cancer

Background: The clinical utility of a blood-based biomarker in squamous cell carcinoma of the anus (SCCA) is unknown. We analyzed carcinoembryonic antigen (CEA), a commonly employed assay for patients with colorectal adenocarcinoma, as a serum biomarker for patients with biopsy-proven SCCA. Materials and Methods: Medical records from 219 patients with biopsy-proven SCCA at the University of Texas MD Anderson Cancer Center were reviewed under an IRB-approved protocol from 2013 to 2020 to assess for correlations between CEA levels and corresponding clinical and pathologic characteristics. Results: The mean CEA among subgroups by clinical status at the time of presentation to our institution was highest among those patients with metastatic SCCA to visceral organs (M-V, 20.7 ng/mL), however this finding was not statistically significant by ANOVA (p = .74). By clinical subgroup, the percentage of patients with an abnormally elevated CEA was highest in those patients with metastatic disease to lymph nodes (M-L, 41.2%) followed by recurrent/unresectable SCCA (36.8%), and metastatic SCCA to visceral organs (M-V, 35.2%), and was statistically significant between groups (Fisher’s exact test p = .02). Using RECIST criteria for tumor progression and disease response, the mean change in CEA for patients with progression was an increase in 19 ng/mL, compared to a change of –7.3 ng/mL in those with disease response (p = .004). We likewise assessed whether CEA levels were associated with survival outcomes for all patients with metastatic SCCA, and found no correlation between CEA and likelihood for survival in a ROC analysis (multivariate, age-adjusted analysis for CEA cutoff of 8, HR = 1.01, 95% CI 0.52–1.96). Conclusions: Despite interesting patterns of abnormally high CEA in SCCA patients with advanced disease, and correlation of increased CEA with disease progression (and conversely decreased CEA with disease response), CEA is not associated with survival outcomes in SCCA, and is not a clinically relevant biomarker in this disease.

[1]  P. Ascierto,et al.  Pembrolizumab for advanced anal squamous cell carcinoma (ASCC): Results from the multicohort, phase II KEYNOTE-158 study. , 2020 .

[2]  A. Jemal,et al.  Cancer statistics, 2020 , 2020, CA: a cancer journal for clinicians.

[3]  A. Vincent-Salomon,et al.  Clinical Validity of HPV Circulating Tumor DNA in Advanced Anal Carcinoma: An Ancillary Study to the Epitopes-HPV02 Trial , 2018, Clinical Cancer Research.

[4]  A. Vincent-Salomon,et al.  Prognostic Impact of Residual HPV ctDNA Detection after Chemoradiotherapy for Anal Squamous Cell Carcinoma , 2018, Clinical Cancer Research.

[5]  C. Brigand,et al.  Surgery Is an Effective Option after Failure of Chemoradiation in Cancers of the Anal Canal and Anal Margin , 2017, Oncology.

[6]  J. Albanell,et al.  Phase Ia and Ib studies of the novel carcinoembryonic antigen (CEA) T-cell bispecific (CEA CD3 TCB) antibody as a single agent and in combination with atezolizumab: Preliminary efficacy and safety in patients with metastatic colorectal cancer (mCRC). , 2017 .

[7]  P. Sharma,et al.  Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study. , 2017, The Lancet. Oncology.

[8]  D. Mant,et al.  Blood Measurement of Carcinoembryonic Antigen Level for Detecting Recurrence of Colorectal Cancer. , 2016, JAMA.

[9]  A. Rashid,et al.  Clinicopathologic Features Associated With Human Papillomavirus/p16 in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal. , 2015, The oncologist.

[10]  S. Devesa,et al.  Anal Cancer Incidence in the United States, 1977–2011: Distinct Patterns by Histology and Behavior , 2015, Cancer Epidemiology, Biomarkers & Prevention.

[11]  B. Vogelstein,et al.  PD-1 blockade in tumors with mismatch repair deficiency. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  T. Vuong,et al.  Squamous anal cancer: patient characteristics and HPV type distribution. , 2013, Cancer epidemiology.

[13]  J. Ledermann,et al.  Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. , 2013, The Lancet. Oncology.

[14]  Charles R. Thomas,et al.  Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  H. Adami,et al.  [Sexually transmitted infection as a cause of anal cancer]. , 1997, Ugeskrift for laeger.

[16]  B. Morson,et al.  Pathology of anal cancer. , 1968, Proceedings of the Royal Society of Medicine.

[17]  O. Børmer,et al.  Carcinoembryonic antigen in anal carcinoma. , 1992, Acta oncologica.