Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Ovarian cancer: the duplicity of CA125 measurement

Nature Reviews Clinical Oncology volume 7, pages 335–339 (2010)Cite this article

Subjects

Abstract

Since it was first described in 1981, CA125 has held an important role in monitoring patients with ovarian cancer. CA125 is elevated in 80% of patients with epithelial ovarian cancer at initial diagnosis and correlates well with response to therapy. CA125 monitoring is used for the follow up of patients with epithelial ovarian cancer, and elevations in CA125 measurements often antedate any signs, symptoms or radiographic evidence of disease by several months. Unfortunately, data favoring early therapeutic intervention for recurrent ovarian cancer is lacking, especially in patients with isolated CA125 elevations. In asymptomatic patients, elevations in CA125 have been associated with considerable anxiety and deterioration in quality of life without any significant gains in survival. Patients with ovarian cancer should, therefore, be counseled regarding the advantages and shortcomings of intensive CA125 testing. While some patients may benefit from early detection of recurrent disease and be candidates for secondary cytoreductive surgery, others may choose to delay therapy until they develop symptoms of disease recurrence. The results of a clinical trial suggest that withholding treatment in the event of isolated rising CA125 levels will not negatively impact these patients overall survival, highlighting the need for improved salvage therapies for recurrent ovarian cancer.

Key Points

  • Despite years of research the function of CA125 remains elusive

  • CA125 correlates well with response to initial therapy but suffers from poor specificity for the diagnosis of early ovarian cancer

  • In the follow-up of patients with epithelial ovarian cancer, elevations in CA125 often antedate any signs, symptoms or radiographic evidence of disease by several months

  • Data favoring early therapy for recurrent ovarian cancer are lacking especially in asymptomatic patients with isolated elevations in their CA125 measurements

  • Patients with epithelial ovarian cancer should be appropriately counseled regarding the advantages and shortcomings of CA125 testing

  • Patients may choose to delay therapy until they develop signs and symptoms of disease recurrence in the event of isolated rising CA125 levels

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: MRC OV05/EORTC 55955 Trial schema.

Similar content being viewed by others

References

  1. Bast, R. C. Jr et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J. Clin. Invest. 6 8, 1331–1337 (1981).

    Article  Google Scholar 

  2. Bast, R. C. Jr et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N. Engl. J. Med. 309, 883–887 (1983).

    Article  Google Scholar 

  3. Partridge, E. et al. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet. Gynecol. 113, 775–782 (2009).

    Article  CAS  Google Scholar 

  4. Menon, U. et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 10, 327–340 (2009).

    Article  Google Scholar 

  5. Rustin, G. J., van der Burg, M. E., on behalf of MRC and EORTC collaborators. A randomized trial in ovarian cancer (OC) of early treatment of relapse based on CA125 level alone versus delayed treatment based on conventional clinical indicators (MRC OV05/EORTC 55955 trials) [abstract]. J. Clin. Oncol. 27 (Suppl. 18s), a1 (2009).

    Article  Google Scholar 

  6. Menczer, J. Re: “clinical implications of a rising serum CA-125 within the normal range in patients with epithelial ovarian cancer: a preliminary investigation”. Gynecol. Oncol. 96, 906–907; author reply 907 (2005).

    Article  Google Scholar 

  7. Armstrong, D. K. Relapsed ovarian cancer: challenges and management strategies for a chronic disease. Oncologist 7 (Suppl. 5), 20–28 (2002).

    Article  CAS  Google Scholar 

  8. O'Brien, T. J. et al. The CA 125 gene: an extracellular superstructure dominated by repeat sequences. Tumour Biol. 22, 348–366 (2001).

    Article  CAS  Google Scholar 

  9. Yin, B. W. & Lloyd, K. O. Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16. J. Biol. Chem. 276, 27371–27375 (2001).

    Article  CAS  Google Scholar 

  10. Bast, R. C. Jr et al. CA 125: the past and the future. Int. J. Biol. Markers 13, 179–187 (1998).

    Article  CAS  Google Scholar 

  11. Kenemans, P., Verstraeten, A. A., van Kamp, G. J. & von Mensdorff-Pouilly, S. The second generation CA 125 assays. Ann. Med. 27, 107–113 (1995).

    Article  CAS  Google Scholar 

  12. Kenemans, P., van Kamp, G. J., Oehr, P. & Verstraeten, R. A. Heterologous double-determinant immunoradiometric assay CA 125 II: reliable second-generation immunoassay for determining CA 125 in serum. Clin. Chem. 39, 2509–2513 (1993).

    CAS  PubMed  Google Scholar 

  13. Gubbels, J. A. et al. Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol. Cancer 5, 50 (2006).

    Article  Google Scholar 

  14. Rump, A. et al. Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J. Biol. Chem. 279, 9190–9198 (2004).

    Article  CAS  Google Scholar 

  15. Kaneko, O. et al. A binding domain on mesothelin for CA125/MUC16. J. Biol. Chem. 284, 3739–3749 (2009).

    Article  CAS  Google Scholar 

  16. Thapi, D. et al. MUC16 gene expression in human ovarian cancer cells and cisplatin resistance. AACR Meeting Abstracts, a881 (2006).

  17. Thapi, D. et al. MUC16 gene up-regulates gene transcripts associated with cisplatin resistance in human ovarian cancer cells. AACR Meeting Abstracts, a2327 (2007).

  18. Hawkins, R. E., Roberts, K., Wiltshaw, E., Mundy, J. & McCready, V. R. The clinical correlates of serum CA125 in 169 patients with epithelial ovarian carcinoma. Br. J. Cancer 60, 634–637 (1989).

    Article  CAS  Google Scholar 

  19. [No authors listed] Chemotherapy for advanced ovarian cancer. Advanced Ovarian Cancer Trialists Group. Cochrane Database of Systematic Reviews, Issue 1. Art No: CD001418. doi: 10.1002/14651858.CD001418 (2000).

  20. Krivak, T. C., Tian, C., Rose, G. S., Armstrong, D. K. & Maxwell, G. L. A Gynecologic Oncology Group Study of serum CA-125 levels in patients with stage III optimally debulked ovarian cancer treated with intraperitoneal compared to intravenous chemotherapy: an analysis of patients enrolled in GOG 172. Gynecol. Oncol. 115, 81–85 (2009).

    Article  Google Scholar 

  21. Juretzka, M. M. et al. CA125 level as a predictor of progression-free survival and overall survival in ovarian cancer patients with surgically defined disease status prior to the initiation of intraperitoneal consolidation therapy. Gynecol. Oncol. 104, 176–180 (2007).

    Article  CAS  Google Scholar 

  22. Cannistra, S. A. Cancer of the ovary. N. Engl. J. Med. 351, 2519–2529 (2004).

    Article  CAS  Google Scholar 

  23. International Collaborative Ovarian Neoplasm Group. Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet 360, 505–515 (2002).

  24. Ozols, R. F. et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J. Clin. Oncol. 21, 3194–3200 (2003).

    Article  CAS  Google Scholar 

  25. Rustin, G. J., Marples, M., Nelstrop, A. E., Mahmoudi, M. & Meyer, T. Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels. J. Clin. Oncol. 19, 4054–4057 (2001).

    Article  CAS  Google Scholar 

  26. Vergote, I. et al. Re: new guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. Gynecologic Cancer Intergroup. J. Natl Cancer Inst. 92, 1534–1535 (2000).

    Article  CAS  Google Scholar 

  27. Tuxen, M. K., Soletormos, G., Rustin, G. J., Nelstrop, A. E. & Dombernowsky, P. Biological variation and analytical imprecision of CA 125 in patients with ovarian cancer. Scand. J. Clin. Lab Invest. 60, 713–721 (2000).

    Article  CAS  Google Scholar 

  28. Bridgewater, J. A. et al. Comparison of standard and CA-125 response criteria in patients with epithelial ovarian cancer treated with platinum or paclitaxel. J. Clin. Oncol. 17, 501–508 (1999).

    Article  CAS  Google Scholar 

  29. Rustin, G. J., Nelstrop, A. E., Tuxen, M. K. & Lambert, H. E. Defining progression of ovarian carcinoma during follow-up according to CA 125: a North Thames Ovary Group Study. Ann. Oncol. 7, 361–364 (1996).

    Article  CAS  Google Scholar 

  30. Tuxen, M. K., Soletormos, G. & Dombernowsky, P. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up. Scand. J. Clin. Lab Invest. 62, 177–188 (2002).

    Article  CAS  Google Scholar 

  31. Therasse, P. et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J. Natl Cancer Inst. 92, 205–216 (2000).

    Article  CAS  Google Scholar 

  32. Wilder, J. L. et al. Clinical implications of a rising serum CA-125 within the normal range in patients with epithelial ovarian cancer: a preliminary investigation. Gynecol. Oncol. 89, 233–235 (2003).

    Article  CAS  Google Scholar 

  33. Santillan, A. et al. Risk of epithelial ovarian cancer recurrence in patients with rising serum CA-125 levels within the normal range. J. Clin. Oncol. 23, 9338–9343 (2005).

    Article  Google Scholar 

  34. Gadducci, A., Cosio, S., Conte, P. F. & Genazzani, A. R. Consolidation and maintenance treatments for patients with advanced epithelial ovarian cancer in complete response after first-line chemotherapy: a review of the literature. Crit. Rev. Oncol. Hematol. 55, 153–166 (2005).

    Article  Google Scholar 

  35. Eisenhauer, E. A., Vermorken, J. B. & van Glabbeke, M. Predictors of response to subsequent chemotherapy in platinum pretreated ovarian cancer: a multivariate analysis of 704 patients. Ann. Oncol. 8, 963–968 (1997).

    Article  CAS  Google Scholar 

  36. Fleming, L. W. Playing the waiting game ... the asymptomatic patient with recurrent ovarian cancer detected only by rising Ca125 levels. Scott. Med. J. 46, 81–83 (2001).

    Article  CAS  Google Scholar 

  37. Hacker, N. F. & Friedlander, M. Treatment of recurrent ovarian cancer. Chang. Gung. Med. J. 27, 570–577 (2004).

    PubMed  Google Scholar 

  38. Rubin, S. C., Randall, T. C., Armstrong, K. A., Chi, D. S. & Hoskins, W. J. Ten-year follow-up of ovarian cancer patients after second-look laparotomy with negative findings. Obstet. Gynecol. 93, 21–24 (1999).

    CAS  PubMed  Google Scholar 

  39. Rubin, S. C. et al. Prognostic factors for recurrence following negative second-look laparotomy in ovarian cancer patients treated with platinum-based chemotherapy. Gynecol. Oncol. 42, 137–141 (1991).

    Article  CAS  Google Scholar 

  40. Obermair, A. & Sevelda, P. Impact of second look laparotomy and secondary cytoreductive surgery at second-look laparotomy in ovarian cancer patients. Acta Obstet. Gynecol. Scand. 80, 432–436 (2001).

    Article  CAS  Google Scholar 

  41. Greer, B. E. et al. Implications of second-look laparotomy in the context of optimally resected stage III ovarian cancer: a non-randomized comparison using an explanatory analysis: a Gynecologic Oncology Group study. Gynecol. Oncol. 99, 71–79 (2005).

    Article  Google Scholar 

  42. Hurteau, J. et al. A randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with an evaluation of serum vascular endothelial growth factor: A Gynecologic Oncology Group study. Gynecol. Oncol. 116 (Suppl.) a2 (2010).

    Google Scholar 

  43. Janicke, F. et al. Radical surgical procedure improves survival time in patients with recurrent ovarian cancer. Cancer 70, 2129–2136 (1992).

    Article  CAS  Google Scholar 

  44. Segna, R. A., Dottino, P. R., Mandeli, J. P., Konsker, K. & Cohen, C. J. Secondary cytoreduction for ovarian cancer following cisplatin therapy. J. Clin. Oncol. 11, 434–439 (1993).

    Article  CAS  Google Scholar 

  45. Gadducci, A. et al. Complete salvage surgical cytoreduction improves further survival of patients with late recurrent ovarian cancer. Gynecol. Oncol. 79, 344–349 (2000).

    Article  CAS  Google Scholar 

  46. Salani, R. et al. Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome. Cancer 109, 685–691 (2007).

    Article  Google Scholar 

  47. Tay, E. H., Grant, P. T., Gebski, V. & Hacker, N. F. Secondary cytoreductive surgery for recurrent epithelial ovarian cancer. Obstet. Gynecol. 99, 1008–1013 (2002).

    PubMed  Google Scholar 

  48. Ayhan, A. et al. The role of secondary cytoreduction in the treatment of ovarian cancer: Hacettepe University experience. Am. J. Obstet. Gynecol. 194, 49–56 (2006).

    Article  Google Scholar 

  49. Chi, D. S. et al. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer 106, 1933–1939 (2006).

    Article  Google Scholar 

  50. Onda, T. et al. Secondary cytoreductive surgery for recurrent epithelial ovarian carcinoma: proposal for patients selection. Br. J. Cancer 92, 1026–1032 (2005).

    Article  CAS  Google Scholar 

  51. Tebes, S. J. et al. Cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma. Gynecol. Oncol. 106, 482–487 (2007).

    Article  Google Scholar 

  52. Scarabelli, C., Gallo, A. & Carbone, A. Secondary cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma. Gynecol. Oncol. 83, 504–512 (2001).

    Article  CAS  Google Scholar 

  53. Eisenkop, S. M., Friedman, R. L. & Spirtos, N. M. The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma. Cancer 88, 144–153 (2000).

    Article  CAS  Google Scholar 

  54. Harter, P. et al. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Ann. Surg. Oncol. 13, 1702–1710 (2006).

    Article  Google Scholar 

  55. Zang, R. Y. et al. Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: who benefits? Cancer 100, 1152–1161 (2004).

    Article  Google Scholar 

  56. Benedetti Panici, P. et al. Secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer. Ann. Surg. Oncol. 14, 1136–1142 (2007).

    Article  Google Scholar 

  57. Karam, A. K. et al. Tertiary cytoreductive surgery in recurrent ovarian cancer: selection criteria and survival outcome. Gynecol. Oncol. 104, 377–380 (2007).

    Article  Google Scholar 

  58. Guppy, A. E. & Rustin, G. J. CA125 response: can it replace the traditional response criteria in ovarian cancer? Oncologist 7, 437–443 (2002).

    Article  CAS  Google Scholar 

  59. Parker, P. A. et al. The associations between knowledge, CA125 preoccupation, and distress in women with epithelial ovarian cancer. Gynecol. Oncol. 100, 495–500 (2006).

    Article  Google Scholar 

  60. Havrilesky, L. J. et al. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol. Oncol. 110, 374–382 (2008).

    Article  CAS  Google Scholar 

  61. Allard, J., Somers, E., Theil, R. & Moore, R. G. Use of a novel biomarker HE4 for monitoring patients with epithelial ovarian cancer [abstract]. J. Clin. Oncol. 26, a5535 (2008).

    Article  Google Scholar 

  62. [No authors listed] BiPar Sciences presents interim phase 2 results for PARP inhibitor BSI-201 at San Antonio Breast Cancer Symposium. Cancer Biol. Ther. 8, 2–3 (2009).

  63. Burger, R. A., Sill, M. W., Monk, B. J., Greer, B. E. & Sorosky, J. I. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J. Clin. Oncol. 25, 5165–5171 (2007).

    Article  CAS  Google Scholar 

  64. Rauh-Hain, J. A. & Penson, R. T. Potential benefit of sunitinib in recurrent and refractory ovarian clear cell adenocarcinoma. Int. J. Gynecol. Cancer 18, 934–936 (2008).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology at the David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS 24-130, Los Angeles, 90095, CA, USA

    Amer K. Karam

  2. Women's Cancer Research Institute at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, 90048, CA, USA

    Beth Y. Karlan

Authors
  1. Amer K. Karam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beth Y. Karlan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beth Y. Karlan.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karam, A., Karlan, B. Ovarian cancer: the duplicity of CA125 measurement. Nat Rev Clin Oncol 7, 335–339 (2010). https://doi.org/10.1038/nrclinonc.2010.44

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2010.44

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer