4.6 Article

CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer-A Multicenter Analysis

Journal

CANCERS
Volume 14, Issue 8, Pages -

Publisher

MDPI
DOI: 10.3390/cancers14081954

Keywords

ovarian cancer; low-grade serous cancer; CA-125; survival

Categories

Funding

  1. Ovarian Cancer Research Fund [PPD/RPCI.07]
  2. US National Cancer Institute GAME-ON Post-GWAS Initiative [U19-CA148112]
  3. Wellcome Trust [076113]
  4. U.S. National Institutes of Health [U19-CA148112, CA1X01HG007491-01, R01-CA149429, R01-CA058598]
  5. Canadian Institutes of Health Research [MOP-86727]
  6. Ovarian Cancer Research Fund
  7. European Commission's Seventh Framework Programme [223175-HEALTH-F2-2009-223175]
  8. U.S. Army Medical Research and Materiel Command [DAMD17-01-1-0729]
  9. National Health & Medical Research Council of Australia [199600, 400413, 400281]
  10. Cancer Council of New South Wales
  11. Cancer Council of Victoria
  12. Cancer Council of Queensland
  13. Cancer Council of South Australia
  14. Cancer Council of Tasmania
  15. Cancer Foundation of Western Australia (Multi-State Applications) [191, 211, 182]
  16. Ovarian Cancer Australia
  17. Peter MacCallum Foundation
  18. National Kankerplan
  19. Ministry of Health, Labour and Welfare
  20. National Cancer Institute, Bethesda [R01- CA61107]
  21. Danish Cancer Society, Copenhagen, Denmark [94 222 52]
  22. Mermaid I project
  23. National Institutes of Health [R01-CA122443, P30-CA15083, P50-CA136393, R01-CA76016]
  24. Mayo Foundation
  25. Minnesota Ovarian Cancer Alliance
  26. Fred C. and Katherine B. Andersen Foundation
  27. Department of Defense [DAMD17-02-1-0666]
  28. Helse Vest
  29. Norwegian Cancer Society
  30. Research Council of Norway
  31. National Health and Medical Research Council (NHMRC) of Australia [APP1025142, APP1120431]
  32. Brisbane Women's Club
  33. Sherie Hildreth Ovarian Cancer (SHOC) Foundation
  34. Cancer Research UK [C536/A13086, C536/A6689]
  35. Imperial Experimental Cancer Research Centre [C1312/A15589]
  36. Princess Margaret Cancer Centre Foundation-Bridge for the Cure

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This study analyzed data from 176 women with low-grade serous ovarian cancer through a multi-center collaborative effort, revealing that elevated post-treatment CA-125 levels are significantly associated with poor survival, while FIGO staging and residual disease also impact patient outcomes.
Simple Summary Low-grade serous cancer (LGSC) accounts for approximately 5% of all ovarian cancers. It is characterized by its high resistance to chemotherapy. Cytoreductive surgery, therefore, is the primary treatment modality for this disease and previous studies have shown that complete removal of all visible tumor tissue should be achieved. In this study, 176 women with LGSC were included and most of them had advanced disease stages, where the disease had already spread. CA-125 is a biomarker that has been previously studied in ovarian cancer. We have found that CA-125 level following treatment of LGSC is an important and independent prognostic factor for progression-free and overall survival. It may be a better surrogate for the true amount of residual disease following treatment compared to the gross estimation of visible residual disease during surgery. Objective: Studies on low-grade serous ovarian cancer (LGSC) are limited by a low number of cases. The aim of this study was to define the prognostic significance of age, stage, and CA-125 levels on survival in a multi-institutional cohort of women with pathologically confirmed LGSC. Methods: Women with LGSC were identified from the collaborative Ovarian Cancer Association Consortium (OCAC). Cases of newly diagnosed primary LGSC were included if peri-operative CA-125 levels were available. Age at diagnosis, FIGO stage, pre- and post-treatment CA-125 levels, residual disease, adjuvant chemotherapy, disease recurrence, and vital status were collected by the participating institutions. Progression-free (PFS) and overall survival (OS) were calculated. Multivariable (MVA) Cox proportional hazard models were used and hazard ratios (HR) calculated. Results: A total of 176 women with LGSC were included in this study; 82% had stage III/IV disease. The median PFS was 2.3 years and the median OS was 6.4 years. Age at diagnosis was not significantly associated with worse PFS (p = 0.23) or OS (p = 0.3) (HR per year: 0.99; 95%CI, 0.96-1.01 and 0.98; 95%CI 0.95-1.01). FIGO stage III/IV was independently associated with PFS (HR 4.26, 95%CI 1.43-12.73) and OS (HR 1.69, 95%CI 0.56-5.05). Elevated CA-125 (>= 35 U/mL) at diagnosis was not significantly associated with worse PFS (p = 0.87) or OS (p = 0.78) in MVA. Elevated CA-125 (>= 35 U/mL) after completion of primary treatment was independently associated with worse PFS (HR 2.81, 95%CI 1.36-5.81) and OS (HR 6.62, 95%CI 2.45-17.92). In the MVA, residual disease was independently associated with PFS (0.022), but not OS (0.85). Conclusion: Advanced LGSC was associated with poor long-term prognosis. FIGO stage and abnormal post-treatment CA-125 level are key prognostic factors inversely associated with PFS and OS. Highlights: 1. Through a multi-center collaborative effort, data from 176 women with low-grade serous ovarian cancer were analyzed. 2. Although low-grade serous ovarian cancer is often considered indolent, the progression-free and overall survival are poor. 3. Elevated post-treatment CA-125 levels are independently associated with poor survival.

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