Adjuvant chemotherapy is not associated with improved overall survival with stage I endometrioid ovarian cancer patients in a SEER cohort

The objectives of this study was to investigate the prognostic significance of adjuvant chemotherapy in early-stage endometrioid ovarian cancer (EnOC) patients, especially those with grade II stage IA and IB and grade I stage IC, that are not explicitly recommended in the current National Comprehensive Cancer Network (NCCN) guidelines. This was a retrospective cohort study based on the Surveillance, Epidemiology and End Results (SEER) database, comprising 875 cases diagnosed with stage I EnOC from 2010 to 2018, of whom 441 (50%) and 434 (50%) received and did not receive chemotherapy, respectively. The Kaplan-Meier method was used for survival analysis, and the Cox multivariate regression analysis was performed to identify independent prognostic factors. Stratified survival analysis for adjuvant chemotherapy based on the recommendations of the NCCN Guidelines in stage I EnOC patients with different substages and grades showed that in this cohort adjuvant chemotherapy did not improve the survival of any of the stage I stratified substages group (p = 0.076, HR: 0.600, 95% CI: 0.342–1.054). Age ≥60 (p = 0.000, HR: 3.609, 95% CI: 2.156–6.039) and elevated CA125 (p = 0.028, HR: 2.480, 95% CI: 1.103–5.577) were independent risk factors associated with worse survival in stage I EnOC patients. In conclusion, chemotherapy would be unnecessary for stage I EnOC patients to improve the overall survival no matter substage and grade in our cohort.

Adjuvant chemotherapy; Stage I; Endometrioid carcinoma; SEER Program

[1] Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, Harvey JD, et al. Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019: a systematic analysis for the global burden of disease study 2019. JAMA Oncology. 2022; 8: 420–444.

[2] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2021; 71: 209–249.

[3] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA: A Cancer Journal for Clinicians. 2021; 71: 7–33.

[4] Huang CY, Cheng NM, Wang PH. Risk factors associated with epithelial ovarian cancer in women with endometriosis. Taiwanese Journal of Obstetrics & Gynecology. 2020; 59: 353–355.

[5] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68: 394–424.

[6] Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA: A Cancer Journal for Clinicians. 2018; 68: 284–296.

[7] Pierson WE, Peters PN, Chang MT, Chen LM, Quigley DA, Ashworth A, et al. An integrated molecular profile of endometrioid ovarian cancer. Gynecologic Oncology. 2020; 157: 55–61.

[8] Nasioudis D, Latif NA, Simpkins F, Cory L, Giuntoli RL 2nd, Haggerty AF, et al. Adjuvant chemotherapy for early stage endometrioid ovarian carcinoma: an analysis of the National Cancer Data Base. Gynecologic Oncology. 2020; 156: 315–319.

[9] Kumar A, Le N, Tinker AV, Santos JL, Parsons C, Hoskins PJ. Early-stage endometrioid ovarian carcinoma: population-based outcomes in british columbia. International Journal of Gynecologic Cancer. 2014; 24: 1401–1405.

[10] Oseledchyk A, Leitao MM Jr, Konner J, O’Cearbhaill RE, Zamarin D, Sonoda Y, et al. Adjuvant chemotherapy in patients with stage I endometrioid or clear cell ovarian cancer in the platinum era: a surveillance, epidemiology, and end results cohort study, 2000–2013. Annals of Oncology. 2017; 28: 2985–2993.

[11] Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, et al. International collaborative ovarian neoplasm trial 1 and adjuvant chemotherapy in ovarian neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. Journal of the National Cancer Institute. 2003; 95: 105–112.

[12] Satoh T, Hatae M, Watanabe Y, Yaegashi N, Ishiko O, Kodama S, et al. Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer: a proposal for patient Selection. Journal of Clinical Oncology. 2010; 28: 1727–1732.

[13] Hall E, Finch A, Jacobson M, Rosen B, Metcalfe K, Sun P, et al. Effects of bilateral salpingo-oophorectomy on menopausal symptoms and sexual functioning among women with a BRCA1 or BRCA2 mutation. Gynecologic Oncology. 2019; 152: 145–150.

[14] Li S, Zhu Z. Chemotherapy is not necessary for early-stage serous and endometrioid ovarian cancer after undergoing comprehensive staging surgery. Journal of Ovarian Research. 2020; 13: 91.

[15] Dinkelspiel HE, Tergas AI, Zimmerman LA, Burke WM, Hou JY, Chen L, et al. Use and duration of chemotherapy and its impact on survival in early-stage ovarian cancer. Gynecologic Oncology. 2015; 137: 203–209.

[16] Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, et al. Rethinking ovarian cancer: recommendations for improving outcomes. Nature Reviews Cancer. 2011; 11: 719–725.

[17] Köbel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Medicine. 2008; 5: e232.

[18] Young RC, Walton LA, Ellenberg SS, Homesley HD, Wilbanks GD, Decker DG, et al. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. The New England Journal of Medicine. 1990; 322: 1021–1027.

[19] Chan JK, Tian C, Fleming GF, Monk BJ, Herzog TJ, Kapp DS, et al. The potential benefit of 6 vs. 3 cycles of chemotherapy in subsets of women with early-stage high-risk epithelial ovarian cancer: an exploratory analysis of a gynecologic oncology group study. Gynecologic Oncology. 2010; 116: 301–306.

[20] Colombo N, Sessa C, Bois AD, Ledermann J, McCluggage W, McNeish I, et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. International Journal of Gynecologic Cancer. 2019; 29: 728–760.

[21] Crafton SM, Cohn DE, Llamocca EN, Louden E, Rhoades J, Felix AS. Fertility‐sparing surgery and survival among reproductive-age women with epithelial ovarian cancer in 2 cancer registries. Cancer. 2020; 126: 1217–1224.

[22] Hollis RL, Thomson JP, Stanley B, Churchman M, Meynert AM, Rye T, et al. Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome. Nature Communications. 2020; 11: 4995.