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Original Research| Volume 66, P114-124, October 2016

Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group, GINECO and NSGO

Published:August 25, 2016DOI:https://doi.org/10.1016/j.ejca.2016.07.014

      Highlights

      • To detect the effect of young age on survival in ovarian cancer patients.
      • A meta-database analysis of 5055 ovarian cancer patients.
      • Potential confounding and effect measure modification are considered.
      • Prognostic factors of survival are similar in patients under and over 40 years of age.
      • Young age at diagnosis of ovarian cancer improves survival.

      Abstract

      Objectives

      We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients < and >40 years of age with advanced epithelial ovarian cancer.

      Methods

      A total of 5055 patients of the AGO, GINECO, NSGO intergroup studies AGO-OVAR 3, 5, 7 and 9 were merged to identify 294 patients <40 years and 4761 patients ≥40 years. We conducted survival analyses and Cox proportional hazard regression models and additionally analysed a very homogeneous subcohort of 405 patients with serous epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and ≥5 chemotherapy cycles.

      Results

      For patients <40 years, the median PFS was 28.9 months and the median OS was 75.3 months, while the median PFS for patients ≥40 years was 18.1 months and the median OS was 45.7 months. Independent prognostic factors were similar in both age groups. In a multivariate analysis including prognostic factors potentially leading to confounding, young age appeared to improve PFS (hazard ratio [HR], 0.86; 95% confidence interval [CI]: 0.72–1.03) and OS (HR, 0.73; 95% CI: 0.59–0.91). The observed effect was even stronger in the subcohort of optimally treated patients with SEOC: PFS (HR, 0.34; 95% CI: 0.19–0.59) and OS (HR, 0.23; 95% CI: 0.09–0.56).

      Discussion

      Prognostic factors were similar in both age groups. Young age appeared a strong independent protective prognostic factor for PFS and OS in the subcohort.

      Keywords

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      References

        • De Angelis R.
        • Sant M.
        • Coleman M.P.
        • Francisci S.
        • Baili P.
        • Pierannunzio D.
        • et al.
        Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5-a population-based study.
        Lancet Oncol. 2013; https://doi.org/10.1016/S1470-2045(13)70546-1
        • Winter 3rd, W.E.
        • Maxwell G.L.
        • Tian C.
        • Sundborg M.J.
        • Rose G.S.
        • Rose P.G.
        • et al.
        Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study.
        J Clin Oncol. 2007; 25: 3621-3627https://doi.org/10.1200/JCO.2006.10.2517
        • Holschneider C.H.
        • Berek J.S.
        Ovarian cancer: epidemiology, biology, and prognostic factors.
        Semin Surg Oncol. 2000; 19: 3-10
        • Xu L.
        • Cai J.
        • Yang Q.
        • Ding H.
        • Wu L.
        • Li T.
        • et al.
        Prognostic significance of several biomarkers in epithelial ovarian cancer: a meta-analysis of published studies.
        J Cancer Res Clin Oncol. 2013; 139: 1257-1277https://doi.org/10.1007/s00432-013-1435-z
        • de la Rochefordiere A.
        • Asselain B.
        • Scholl S.
        • Campana F.
        • Ucla L.
        • Vilcoq J.R.
        • et al.
        Age as prognostic factor in premenopausal breast carcinoma.
        Lancet. 1993; 341: 1039-1043
        • Walker R.A.
        • Lees E.
        • Webb M.B.
        • Dearing S.J.
        Breast carcinomas occurring in young women (< 35 years) are different.
        Br J Cancer. 1996; 74: 1796-1800
        • Kroman N.
        • Jensen M.B.
        • Wohlfahrt J.
        • Mouridsen H.T.
        • Andersen P.K.
        • Melbye M.
        Factors influencing the effect of age on prognosis in breast cancer: population based study.
        BMJ. 2000; 320: 474-478
      1. Cancer statistics review, 1975-2010-SEER statistics. Available at: http://seer.cancer.gov/csr/1975_2010/. [accessed 27.03.14].

        • Pfisterer J.
        • Weber B.
        • Reuss A.
        • Kimmig R.
        • du Bois A.
        • Wagner U.
        • et al.
        Randomized phase III trial of topotecan following carboplatin and paclitaxel in first-line treatment of advanced ovarian cancer: a gynecologic cancer intergroup trial of the AGO-OVAR and GINECO.
        J Natl Cancer Inst. 2006; 98: 1036-1045https://doi.org/10.1093/jnci/djj296
        • du Bois A.
        • Lück H.J.
        • Meier W.
        • Adams H.P.
        • Möbus V.
        • Costa S.
        • et al.
        A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer.
        J Natl Cancer Inst. 2003; 95: 1320-1329
        • du Bois A.
        • Weber B.
        • Rochon J.
        • Meier W.
        • Goupil A.
        • Olbricht S.
        • et al.
        Addition of epirubicin as a third drug to carboplatin-paclitaxel in first-line treatment of advanced ovarian cancer: a prospectively randomized gynecologic cancer intergroup trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens.
        J Clin Oncol. 2006; 24: 1127-1135https://doi.org/10.1200/JCO.2005.03.2938
        • du Bois A.
        • Herrstedt J.
        • Hardy-Bessard A.C.
        • Müller H.H.
        • Harter P.
        • Kristensen G.
        • et al.
        Phase III trial of carboplatin plus paclitaxel with or without gemcitabine in first-line treatment of epithelial ovarian cancer.
        J Clin Oncol. 2010; 28: 4162-4169https://doi.org/10.1200/JCO.2009.27.4696
        • Yancik R.
        Ovarian cancer. Age contrasts in incidence, histology, disease stage at diagnosis, and mortality.
        Cancer. 1993; 71: 517-523
        • Wimberger P.
        • Lehmann N.
        • Kimmig R.
        • Burges A.
        • Meier W.
        • Hoppenau B.
        • et al.
        Impact of age on outcome in patients with advanced ovarian cancer treated within a prospectively randomized phase III study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group (AGO-OVAR).
        Gynecol Oncol. 2006; 100: 300-307https://doi.org/10.1016/j.ygyno.2005.08.029
        • Pignata S.
        • Vermorken J.B.
        Ovarian cancer in the elderly.
        Crit Rev Oncol Hematol. 2004; 49: 77-86
        • Hightower R.D.
        • Nguyen H.N.
        • Averette H.E.
        • Hoskins W.
        • Harrison T.
        • Steren A.
        National survey of ovarian carcinoma. IV: patterns of care and related survival for older patients.
        Cancer. 1994; 73: 377-383
        • Jørgensen T.L.
        • Teiblum S.
        • Paludan M.
        • Poulsen L.Ø.
        • Jørgensen A.Y.
        • Bruun K.H.
        • et al.
        Significance of age and comorbidity on treatment modality, treatment adherence, and prognosis in elderly ovarian cancer patients.
        Gynecol Oncol. 2012 Nov; 127: 367-374
        • Bozas G.
        • Dimopoulos M.A.
        • Kastritis E.
        • Efstathiou E.
        • Koutsoukou V.
        • Rodolakis A.
        • et al.
        Young age is associated with favorable characteristics but is not an independent prognostic factor in patients with epithelial ovarian cancer: a single institution experience.
        Oncology. 2006; 70: 265-272https://doi.org/10.1159/000094889
        • Duska L.R.
        • Chang Y.C.
        • Flynn C.E.
        • Chen A.H.
        • Goodman A.
        • Fuller A.F.
        • et al.
        Epithelial ovarian carcinoma in the reproductive age group.
        Cancer. 1999; 85: 2623-2629
        • Massi D.
        • Susini T.
        • Savino L.
        • Boddi V.
        • Amunni G.
        • Colafranceschi M.
        Epithelial ovarian tumors in the reproductive age group: age is not an independent prognostic factor.
        Cancer. 1996; 77: 1131-1136
        • Thigpen T.
        • Brady M.F.
        • Omura G.A.
        • Creasman W.T.
        • McGuire W.P.
        • Hoskins W.J.
        • et al.
        Age as a prognostic factor in ovarian carcinoma. The Gynecologic Oncology Group experience.
        Cancer. 1993; 71: 606-614
        • Lee C.K.
        • Pires de Miranda M.
        • Ledermann J.A.
        • Ruiz de Elvira M.C.
        • Nelstrop A.E.
        • Lambert H.E.
        • et al.
        Outcome of epithelial ovarian cancer in women under 40 years of age treated with platinum-based chemotherapy.
        Eur J Cancer. 1999; 35: 727-732
        • Xiao Q.
        • Yang H.P.
        • Wentzensen N.
        • Hollenbeck A.
        • Matthews C.E.
        Physical activity in different periods of life, sedentary behavior, and the risk of ovarian cancer in the NIH-AARP diet and health study.
        Cancer Epidemiol Biomarkers Prev. 2013; 22: 2000-2008https://doi.org/10.1158/1055-9965.EPI-13-0154
        • Péus D.
        • Newcomb N.
        • Hofer S.
        Appraisal of the Karnofsky Performance Status and proposal of a simple algorithmic system for its evaluation.
        BMC Med Inform Decis Mak. 2013; 13: 72https://doi.org/10.1186/1472-6947-13-72
        • Claus E.B.
        • Schildkraut J.M.
        • Thompson W.D.
        • Risch N.J.
        The genetic attributable risk of breast and ovarian cancer.
        Cancer. 1996; 77: 2318-2324https://doi.org/10.1002/(SICI)1097-0142(19960601)77:11<2318::AID-CNCR21>3.0.CO;2-Z
        • Rudaitis V.
        • Zvirblis T.
        • Kanopiene D.
        • Janulynaite D.
        • Griskevicius L.
        • Janavicius R.
        BRCA1/2 mutation status is an independent factor of improved survival for advanced (stage III–IV) ovarian cancer.
        Int J Gynecol Cancer. 2014 Oct; 24: 1395-1400
        • Alsop K.
        • Fereday S.
        • Meldrum C.
        • deFazio A.
        • Emmanuel C.
        • George J.
        • et al.
        BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group.
        J Clin Oncol. 2012 Jul 20; 30: 2654-2663
        • Harter Philipp
        • Hauke Jan
        • Heitz Florian
        • Reuss Alexander
        • Kommoss Stefan
        • Marme Frederik
        • et al.
        Incidence of germline mutations in risk genes including BRCA1/2 in consecutive ovarian cancer (OC) patients (AGO TR-1).
        J Clin Oncol. 2016; 34 (suppl; abstr 5538)
        • Omura G.A.
        • Brady M.F.
        • Homesley H.D.
        • Yordan E.
        • Major F.J.
        • Buchsbaum H.J.
        • et al.
        Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience.
        J Clin Oncol. 1991; 9: 1138-1150
        • Mackay H.J.
        • Brady M.F.
        • Oza A.M.
        • Reuss A.
        • Pujade-Lauraine E.
        • Swart A.M.
        • et al.
        Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer.
        Int J Gynecol Cancer. 2010; 20: 945-952https://doi.org/10.1111/IGC.0b013e3181dd0110