CA-125 Levels Are Predictive of Survival in Low-Grade Serous Ovarian Cancer—A Multicenter Analysis
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 1954 |
| Tidsskrift | Cancers |
| Vol/bind | 14 |
| Udgave nummer | 8 |
| Antal sider | 12 |
| ISSN | 2072-6694 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Funding: The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The OCAC OncoArray genotyping project was funded through grants from the U.S. National Institutes of Health (CA1X01HG007491-01 (C.I.A.), U19-CA148112 (T.A.S.), R01-CA149429 (C.M.P.) and R01-CA058598 (M.T.G.); Canadian Institutes of Health Research (MOP-86727 (L.E.K.) and the Ovarian Cancer Research Fund (A.B.). The COGS project was funded through a European Commission’s Seventh Framework Programme grant (agreement number 223175—HEALTH-F2-2009-223175). Funding for individual studies: AUS: The Australian Ovarian Cancer Study (AOCS) was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182). AOCS gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; BEL: National Kankerplan; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; MAL: Funding for this study was provided by research grant R01-CA61107 from the National Cancer Institute, Bethesda, MD, research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I project; MAY: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; NCO: National Institutes of Health (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666); NOR: Helse Vest, The Norwegian Cancer Society, The Research Council of Norway; OPL: National Health and Medical Research Council (NHMRC) of Australia (APP1025142, APP1120431) and Brisbane Women’s Club; ORE: Sherie Hildreth Ovarian Cancer (SHOC) Foundation; SRO: Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589); UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure.
Funding Information:
Conflicts of Interest: Penelope M. Webb and Anna DeFazio received grant funding and a speaker’s fee from AstraZeneca for an unrelated study of ovarian cancer. Supporting sources had no involvement in the decision to publish. The other authors report no conflict of interest.
Funding Information:
The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium that was funded by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The OCAC OncoArray genotyping project was funded through grants from the U.S. National Institutes of Health (CA1X01HG007491-01 (C.I.A.), U19-CA148112 (T.A.S.), R01-CA149429 (C.M.P.) and R01-CA058598 (M.T.G.); Canadian Institutes of Health Research (MOP-86727 (L.E.K.) and the Ovarian Cancer Research Fund (A.B.). The COGS project was funded through a European Commission?s Seventh Framework Programme grant (agreement number 223175?HEALTH-F2-2009-223175). Funding for individual studies: AUS: The Australian Ovarian Cancer Study (AOCS) was supported by the U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600, 400413 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania and Cancer Foundation of Western Australia (Multi-State Applications 191, 211, and 182). AOCS gratefully acknowledges additional support from Ovarian Cancer Australia and the Peter MacCallum Foundation; BEL: National Kankerplan; JPN: Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare; MAL: Funding for this study was provided by research grant R01-CA61107 from the National Cancer Institute, Bethesda, MD, research grant 94 222 52 from the Danish Cancer Society, Copenhagen, Denmark; and the Mermaid I project; MAY: National Institutes of Health (R01-CA122443, P30-CA15083, P50-CA136393); Mayo Foundation; Minnesota Ovarian Cancer Alliance; Fred C. and Katherine B. Andersen Foundation; NCO: National Institutes of Health (R01-CA76016) and the Department of Defense (DAMD17-02-1-0666); NOR: Helse Vest, The Norwegian Cancer Society, The Research Council of Norway; OPL: National Health and Medical Research Council (NHMRC) of Australia (APP1025142, APP1120431) and Brisbane Women?s Club; ORE: Sherie Hildreth Ovarian Cancer (SHOC) Foundation; SRO: Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589); UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure. Acknowledgments: We are grateful to the family and friends of Kathryn Sladek Smith for their generous support of the Ovarian Cancer Association Consortium through their donations to the Ovarian Cancer Research Fund. The OncoArray and COGS genotyping projects would not have been possible without the contributions of the following: Per Hall (COGS); Douglas F. Easton, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang (BCAC), Rosalind A. Eeles, Douglas F. Easton, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Antonis Antoniou, Lesley McGuffog, Fergus Couch and Ken Offit (CIMBA), Joe Dennis, Jonathan P. Tyrer, Siddhartha Kar, Alison M. Dunning, Andrew Lee, and Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, Javier Benitez, Anna Gonzalez-Neira and the staff of the CNIO genotyping unit, Jacques Simard and Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissi?re and Frederic Robidoux and the staff of the McGill University and G?nome Qu?bec Innovation Centre, Stig E. Bojesen, Sune F. Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. We pay special tribute to the contribution of Professor Brian Henderson to the GAME-ON consortium; to Olga M. Sinilnikova for her contribution to CIMBA and for her part in the initiation and coordination of GEMO until she sadly passed away on 30 June 2014 and to Catherine M. Phelan for her contribution to OCAC and coordination of the OncoArray until she passed away on 22 September 2017. We thank the study participants, doctors, nurses, clinical and scientific collaborators, health care providers, and health information sources who have contributed to the many studies contributing to this manuscript.
Funding Information:
Acknowledgments: We are grateful to the family and friends of Kathryn Sladek Smith for their generous support of the Ovarian Cancer Association Consortium through their donations to the Ovarian Cancer Research Fund. The OncoArray and COGS genotyping projects would not have been possible without the contributions of the following: Per Hall (COGS); Douglas F. Easton, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang (BCAC), Rosalind A. Eeles, Douglas F. Easton, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Antonis Antoniou, Lesley McGuffog, Fergus Couch and Ken Offit (CIMBA), Joe Dennis, Jonathan P. Tyrer, Siddhartha Kar, Alison M. Dunning, Andrew Lee, and Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, Javier Benitez, Anna Gonzalez-Neira and the staff of the CNIO genotyping unit, Jacques Simard and Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissière and Frederic Robidoux and the staff of the McGill University and Génome Québec Innovation Centre, Stig E. Bojesen, Sune F. Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. We pay special tribute to the contribution of Professor Brian Henderson to the GAME-ON consortium; to Olga M. Sinilnikova for her contribution to CIMBA and for her part in the initiation and coordination of GEMO until she sadly passed away on 30 June 2014 and to Catherine M. Phelan for her contribution to OCAC and coordination of the OncoArray until she passed away on 22 September 2017. We thank the study participants, doctors, nurses, clinical and scientific collaborators, health care providers, and health information sources who have contributed to the many studies contributing to this manuscript. Acknowledgements for individual studies: AUS: The AOCS also acknowledges the cooperation of the participating institutions in Australia, and the contribution of the study nurses, research assistants and all clinical and scientific collaborators. The complete AOCS Study Group can be found at www.aocstudy.org, accessed on 1 April 2022. We would like to thank all of the women who participated in this research program; BEL: We would like to thank Gilian Peuteman, Thomas Van Brussel, Annick Van den Broeck and Joke De Roover for technical assistance; OPL: Members of the OPAL Study Group (http://opalstudy.qimrberghofer.edu.au, accessed on 1 April 2022); SRO: We would like to thank all members of the Scottish Gynaecological Clinical Trials group and SCOTROC1 investigators; UHN: Princess Margaret Cancer Centre Foundation-Bridge for the Cure.
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© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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