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Accuracy of surveillance serum squamous cell carcinoma antigen for cervical cancer recurrence after definitive chemoradiation
  1. Victoria Shi1,
  2. Surbhi Grover2,
  3. Yi Huang1,
  4. Premal H Thaker3,
  5. Lindsay M Kuroki3,
  6. Matthew A Powell3,
  7. David G Mutch3,
  8. Jessika A Contreras1,
  9. Julie K Schwarz1,
  10. Perry W Grigsby1 and
  11. Stephanie Markovina1
    1. 1 Radiation Oncology, Washington University in St Louis, St Louis, Missouri, USA
    2. 2 Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
    3. 3 Obstetrics and Gynecology, Washington University in St Louis, St Louis, Missouri, USA
    1. Correspondence to Dr Stephanie Markovina, Radiation Oncology, Washington University in St Louis, St Louis 63110, Missouri, USA; smarkovina{at}wustl.edu

    Abstract

    Objective Recurrence remains a significant clinical problem for patients with cervical cancer, and early detection may improve outcomes. Serum squamous cell carcinoma antigen (SCCA) is a biomarker of prognosis and response to chemoradiotherapy. We hypothesized that elevated serum SCCA during surveillance is sensitive and specific for recurrence.

    Methods Pre-treatment and follow-up serum SCCA from patients treated with definitive-intent radiotherapy were measured via enzyme-linked immunosorbent assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory and analyzed retrospectively. Follow-up SCCA was defined as the value closest to recurrence, or as last available for patients without recurrence. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of follow-up SCCA for recurrence was determined for the whole cohort (Cohort 1), for patients with elevated (Cohort 2), and normal pre-treatment SCCA (Cohort 3). Patterns of failure were also evaluated.

    Results Of 227 patients in Cohort 1, 23% experienced recurrence, and 17% died of cervical cancer. Mean follow-up SCCA was 0.9 (±2.5) for patients with no recurrence and 6.0 (±18.7) for patients with recurrence (p=0.02). Sensitivity, specificity, PPV, and NPV of follow-up SCCA for recurrence in Cohort 1 were 38.5%, 97.1%, 80%, and 84.2%, and for patients in Cohort 2 were 54.5%, 95%, 78.3%, and 86.5%, respectively. Four of 86 patients in Cohort 3 had an elevated follow-up SCCA, two of these at the time of recurrence. Elevated pre-treatment SCCA and follow-up SCCA were associated with isolated pelvic recurrence.

    Conclusions Surveillance serum SCCA has high specificity and NPV for recurrence, and may be of limited utility in patients with normal pre-treatment SCCA.

    • Cervical Cancer
    • Uterine Cervical Neoplasms
    • Radiotherapy, Image-Guided
    • Radiotherapy, Intensity-Modulated

    Data availability statement

    Data are available upon reasonable request. The data used for this analysis may be available upon request in an anonymized way that is compliant with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and institutional practice under a data-sharing agreement. Only de-identified aggregated data will be provided.

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    Data availability statement

    Data are available upon reasonable request. The data used for this analysis may be available upon request in an anonymized way that is compliant with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and institutional practice under a data-sharing agreement. Only de-identified aggregated data will be provided.

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    Footnotes

    • X @SMarkovina2

    • Contributors VS contributed to conceptualization, methodology, data curation, formal analysis, and writing and editing of the manuscript, SG contributed to conceptualization, methodology, and editing of the manuscript, YH contributed to data curation, formal analysis, and editing of the manuscript, PT, LK, MP, DM, JC, and JS contributed to conceptualization, writing and editing of the manuscript. PG contributed to conceptualization, methodology, data curation, supervision, and editing of the manuscript. SM contributed to conceptualization, methodology, data curation, supervision, writing and editing of the manuscript, and serves as the guarantor of the manuscript. The authors thank Lena Zein for formatting of the manuscript and administrative support.

    • Funding SM is supported by NCI K08 CA237822-01, JKS is supported by U54CA274318 and R01CA181745.

    • Competing interests JS has research grant funding on cervical cancer from the National Institutes for Health (NIH), AACR-Bristol-Myers Squibb Female Investigator Grant. LK serves on the Society of Gynecologic Oncology (SGO) Diversity, Inclusion, Health Equity Committee. MP has grants from GSK, has received consulting fees from Merck, AstraZeneca, GSK/Tesaro, Eisai, Clovis Oncology, Immunogen, Seagen, and serves on committees for NRG Oncology/National Cancer Institute (NCI), Foundation for Women’s Cancer. PT has grant funding from Glaxo Smith Kline, Merck, and consulting fees from Immunon. She serves on the Data Safety Monitoring Board or Advisory Boards for Iovance, Astra Zeneca, Immunon, Novocure, Glaxo Smith Kline, Verastem, Clovis Oncology, Caris, R Pharm, Merck, Mersana, Immunogen, Aadi Pharmaceuticals, Seagen, Zentalis, and has stock options in Immunon. SM has cervical cancer grant funding from the NCI, American Cancer Society, American Society of Clinical Oncology (ASCO) and Conquer Cancer Foundation, leadership or fiduciary role in other board, society, committee or advocacy groups, paid or unpaid: National Comprehensive Cancer Network (NCCN) Thyroid Carcinoma Panel, NRG Oncology – Gynecologic Cancers Radiation Therapy Committee, K12 Paul Calabresi Program in Oncology, Alumni Advisory Council (AAC) Wisconsin Surgical Outcomes Research Program (WiSOR), American Society for Radiation Oncology (ASTRO), MDACC Moonshots Advisory Committee; other financial or non-financial interests: Principal Investigator of clinical trial, ClinicalTrials.gov Identifier: NCT03955978 – TSR-042. SG has grants or contracts from NCI, and receives consulting fees from GenesisCare USA, and speaking honoraria from Varian Medical Systems.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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