Analysis of 114 serous borderline ovarian tumours Vancraeynest E, Moerman Ph, Leunen K, Amant F, Neven P, Vergote I

Aanleiding Onderzoek naar aanleiding van 2 artikels: - Uzan et al [5]: onderzocht PF voor invasief herval en de impact op OS van FPS. Geen invloed op OS na FPS. - Trillsch et al [4]: hoger risico op herval bij jongere populatie zonder verhoogd risico op invasief herval. Echter hoger risico op invasief herval bij oudere populatie.

Doel van de studie Overall survival (OS) en progression-free interval (PFI) Invloed van fertiliteitssparende (FPS) vs radicale chirurgie (RS) op OS en PFI bij patiënten met sereuze borderline tumoren

Sereuze ovariële borderline tumoren 10-20% van ovariële epitheliale tumoren Afwezigheid van destructieve stromale invasie Papillair vs micropapillair 1/3 ≤ 40 jaar 85 % FIGO stadium I OS: 95 % FIGO I, 70-85% FIGO II-IV 11 % herval en 2-4 % invasief herval Lange follow-up gezien laattijdig herval

Methode Retrospectief Primaire diagnose van SBOT (exclusie micro-invasie) Alleen eerste herval 1 patholoog FIGO 2014 classificatie Kaplan-Meier methode voor OS en PFI COX proportional hazards model voor prognostische factoren herval

Patiënt en tumor karakteristieken 114 patiënten 46% ≤ 40 jaar (53 van 114) Mediane leeftijd 44 jaar (17-77j) Mediane FU: 6 jaar (3,8-11,1j) 66% FIGO stadium I (75 van 114) 33% peritoneale implanten, 9% micropapillair

Karakteristieken van behandeling 18% laparoscopie, 82% laparotomie 33% FPS: 76% USO, 16% USO + cystectomie, 8% cystectomie 67% RS: 8% BSO, 87% BSO + HT, 5% USO + HT 71% volledige staging

Herval 12% herval (14/114) 1,7% invasief (2/114)10,5% BOT (12/114) 7 ovarieel 5 ipsilateraal 2 contralateraal 2 USO 3 cystectomie2 USO Tijd tot invasief herval : 59 en 83 maanden Tijd tot BOT herval: 33 maanden

OS en PFI 5j-OS: 97%5j-PFI: 89%

Invloed van FPS vs RS op PFI Risico op progressie is hoger bij patiënten met fertiliteitssparende chirurgie. P=0,0075

Invloed van FPS vs RS op OS Geen statistisch significant verschil in overleving tussen FPS en RS P=0,1125

Prognostische factoren voor herval 95% confidence interval Variable Hazard Ratio Lower limit Upper limitP-valueN obs.N events Age: >40y vs <=40y Surgery: Conservative vs Radical Cons. surg.: cystectomy vs USO Staging: Complete vs incomplete FIGO: III vs I/II Surg.: Laparoscopy vs Laparotomy Type: micropapillary vs papillary Implants: Yes vs No Bilateral BOT vs unilateral Residual tumor: Yes vs No CA125 preop (+1000 U/l) Binary variables: HR>( (<)1: Higher (lower) risk of progression for higher level

Prognostische factoren voor invasief herval Te laag aantal (2) Kenmerken: - Laaggradig - Micropapillaire variant - Niet-invasieve implanten - FIGO III - Levend (88 en 134 maanden na herval)

BESLUIT Uitstekende prognose Kleine kans op herval, invasief herval en overlijden => Fertiliteitssparende chirurgie bij jonge patiënten met stadium I is verantwoord.

Bronnen Trillsch F, Mahner S, Ruetzal JD, Harter P, Ewald-Riegler N, Jaenicke F, Du Bois A. Clinical management of borderline ovarian tumors. Expert review of Anticancer Therapy 2010; 10 (7): Trillsch F, Mahner S, Woelber L, Vettorazzi E, Reuss A, Ewald- Riegler N, et al. Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study. Ann Oncol 2014 March 3; 25 (7): Fischerova D, Zikan M, Dundr P, Cibula D. Diagnosis, treatment and follow-up of borderline ovarian tumors. Gynecol Oncol 2012; 17: Tropé CG, Kaern J, Davidson B. Borderline ovarian tumours. Best Pract Res Clin Obstet Gynaecol## ; 26(3): Morice P, Uzan C, Fauvet R, Sebastien G, Duvillard P, Darai E. Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence. Lancet Oncol 2012; 13: Du Bois A, Ewald-Riegler N, De Gregorio N, Reuss A, Mahner S, Fotopoulou C, et al. Borderline tumours of ovary: A cohort study of the Arbeitsgmeinschaft Gynakologische Onkologie (AGO) study group. Eur J Cancer 2013; 49: Du Bois A, Ewald-Riegler N, Du Bois O, Harter P. Borderlinetumoren des Ovars – eine systematische Übersicht. Geburtshilfe Frauenheilkd 2009; 69: Avril S, Hahn E, Specht K, Hauptmann S, Höss C, Kiechle M, Höfler H, Schmalfeldt B. Histopathologic features of ovarian borderline tumors are not predictive of clinical outcome. Gynecol Oncol 2012; 127: Cadron I, Leunen K, Van Gorp T, Amant F, Neven P, Vergote I. Management of borderline ovarian neoplasms. J Clin Oncol 2007 Jul; 25 (20): Silva EG, Gershenson DM, Malpica A, et al. The recurrence and the overall survival rates of ovarian serous borderline neoplasms with noninvasive implants is time dependent. Am J Surg Pathol 2006; 30: Prat J. The results of conservative (fertility-sparing) treatment in borderline ovarian tumors vary depending on age and histological type. Ann Oncol 2014; 25: Messalli E, Grauso F, Balbi G, Napolitano A, Seguino E, Torella M. Borderline ovarian tumors: features and controversial aspects. Eur J Obstet Gynecol Reprod Biol 2013 Nov 13; 167: Jeong-Yeol P, Dae-Yeon K, Yong-Hyeok K, Yong-Man K, Kyu-Rae K, Young-Tak K, Joo-Hyun N. Micropapillary pattern in serous borderline ovarian tumours: does it matter? Gynecol Oncol 2011 Dec; 123 (3): Uzan C, Nikpayam M, Ribassin-Majed L, Gouy S, Bendifallah S, Cortez A, et al. Influence of histological subtypes on the risk of an invasive recurrence in a large series of stage I borderline ovarian tumor including 191 conservative treatments. Ann Oncol 2014 April 8; 25 (7):

Trimbos JB, Vergote I, Bolis G, Vermorken J, Mangioni C, Madronal C. Impact of adjuvant chemotherapy and surgical staging in early- stage ovarian carcinoma: European organisation for research and treatment of cancer adjuvant chemotherapy in ovarian neoplasm trial. J Natl Cancer Inst 2003; 95 (2): Patrono MG, Minig L, Diaz-Padilla I, Romero N, Rodriguez Moreno JF, Garcia-Donas J. Borderline tumours of the ovary, current controversies regarding their diagnosis and treatment. Ecancermedicalscience 2013; 7: 379. Farthmann J, Hasenburg A, Weil M, Fotopoulou C, Ewald-Riegler N, Bois O, et al. Quality of life and sexual function in patients with borderline tumours of the ovary. A substudy of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) study group ROBOT study. Support Care Cancer 2015; 23 (1): Kennedy AW, Hart WR. Ovarian papillary serous tumors of low malignant potential (serous borderline tumors) – A long term follow- up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma. Cancer 1996; 78 (2): Seidman JD, Kurman RJ. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol 2000 May; 31 (5): Kristensen GS, Schledermann D, Mogensen O, Jochumsen KR. The value of random biopsies, omenectomy, and hysterectomy in operations for borderline ovarian tumors. Int J Gynecol Cancer 2014; 24: Prat J, De Nictolis M. Serous borderline tumors of the ovary. A long- term follow-up study of 137 cases, including 18 with a micropapillary pattern and 20 with microinvasion. Am J Clin Pathol 2002; 26 (9): Höhn AK, Einenkel J, Wittekind C, Horn LC. Neue FIGO- Klassifikation des Ovarial-, Tuben- und primären Peritonealkarzinoms. Pathologe 2014; 35: Fadare O, Oluwole MD. Recent developments on the significance and pathogenesis of lymph node involvement in ovarian serous tumors of low malignant potential (borderline tumors). Int J gynecol Cancer 2009; 19(1): Trillsch F, Mahner S, Vettorazzi E, Woelber L, Reuss A, Baumann K, et al. Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study. Br J Cancer 2015 Jan 6; 1 (1): 1-7. Romeo M, Pons F, Barretina P, Radua J. Incomplete staging surgery as a major predictor of relapse of borderline ovarian tumor. World J Surg Oncol 2013; 11: 1-7. Ewald-Riegler N, Du Bois O, Fisseler-Eckhoff A, Kommoss PH, Traut A, Hils R, Du Bois A. Borderline tumors of the ovary: clinical course and prognostic factors. Oncology 2012; 35: Poncelet C, Fauvet R, Boccara J, Darai E. Recurrence after cystectomy for borderline ovarian tumors: results of a French multicenter study. Ann Surg Oncol 2006; 13: