Fertility-sparing surgery in young patients with cervical cancer

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Fertility-sparing surgery in young patients with cervical cancer Pr Catherine Uzan Chef de service Chirurgie et cancérologie gynécologique et mammaire, Pitié

Evaluation BEFORE surgery Cancer: stage, type Patient s age Desire for future pregnancy Imaging+++ Tumor Board, multidisciplinary decision (oncofertility network) Early specific oncofertility consultation

Key elements to stage Size (volume?) Clinical examination Nodes +/- Pathological review Histology MRI Lympho-vascular space involvement (LVSI) PET CT for advanced stage

IA1, IA2 (microscopic): conization

Conization Obstetrical risks (metanalysis Kirgiou Lancet 2006) Obstetrical risks Odd ratio (OR, IC 95%) Preterm delivery 2.59 (1.80-3.72) Premature rupture of the membranes 2.69 (1.62-4.46) Caesarean section 3.17 (1.07-9.40) Low birth weight (<2500g) 2.53 (1.19-5.36)

2015 6

New french recommandations (INCA) in 2017: Under colposcopy control to limit excision size No systematic second procedure if no margin HPV status more important in follow up 1997-2005 (552 678 singletons, 19049 preterm, 8 180 subsequent to Loop electrosurgical excision procedure): 6% increase in risk of pretem delivery per each additional millimeter of tissue excised (OR: 1,06 95% [1,03-1,09]) LEEP: RRX2 / no LEEP 2 or + LEEP: RR X4 / no LEEP 7

IB1, <2cm, no LVSI, N-: Radical trachelectomy De-escalation? (on going studies)

Radical trachelectomy Technique of Pr Dargent in 1987 Conditions Histological review <2cm No LVSI (discussed, demontrated risk factor) MRI: limited / isthma Desire of pregnancy (fertility?) Examination: size of cervix after previous conization During surgery Pelvic lymphadenectomy Frozen section for margin Definitive cerclage 9

Less radical surgery? Review of rate of parametrial involvement if N-, <2cm, no LVSI: 0.6% (Uzan 2009, Schmeler 2011) Gynecol oncol 2014 3 on going trials ConCerv (Shmeler): cohorte with less radical surgery, 25/100 SHAPE (Plante): randomization radical vs non radical, 700 pts GOG 278 (Covens): quality of life after non radical surgery, 200 to 600 pts

Clinical recommendation radical trachelectomy for fertility preservation in patients with early-stage cervical cancer. Int Gyn Cancer, Schneider et al 2012 Review VRT-ART If < 2 cm, Recurrence rate 3-6% Death rate 2-5% Same fertility Risk of preterm delivery RR=2-3 More info on VRT / ART >2cm, chemo and RT: option but limited experience

Fertility after trachelectomy (Bentivegna fertil steril 2016) Pregnancy rate 55% Live Birth rate 70% Prematurity rate 38% 12

Sexuality after trachelectomy While FSS may allow for post-treatment fertility, it may not confer a significant benefit with regard to sexual satisfaction or sexual QOL. Decision to perform FSS should not be dictated based on preservation of sexual functioning. 13

2-4 cm, N- French standard: Radical hysterectomy (RH) or brachytherapy-rh (5 year survival rate 95% Uzan et al 2012) Option to spare fertility: Neoadjuvant chemotherapy (NAC) trachelectomy / conization

Gynecol oncol 2014 28 patients <35y, > 2 cm or >50% stroma infiltration Dose-dense NAC (cisplatine-ifo for SCC/ cisplatin-doxo for ADK) Pelvic laparoscopy and simple trachelectomy Median FU 42 months 10 lost fertility 10/20 pregnant, 10 babies/ 8 wo (4 preterm) 20% recurred (2/4 DCD)

112 patients Cisplatine-ifosfamide FU / cisplatine ifosfamide placitaxel 6 recurrences (4 /28 in the largest series ) Review Bentivegna et al Lancet oncol 2016 16

> 4cm: Standard Chemo-radiation Brachytherapy Option to spare fertility: NAC trachelectomy???

N+ Standard Chemo-radiation Brachytherapy Option to spare fertility: NO

To inform patients Risk of non eligibility during surgery (N+ or invaded margin in frozen section) Switch to Chemo-radiation if N+ Results on fertility and pregnancy after this procedure De-escalation of surgery for limited lesions? Increase indications of conservative treatment???

How to improve our management? To evaluate stage, desire and needs of the patient To anticipate Risk of modification of treatment planification Explain all the possibilities Evolution of treatments (up-to-date) To collaborate Imaging Early consultation in oncofertility (network) Learn from one other-international register (patient included)

Brannstrom team Lancet 2014 Easier to preserve than to restore (for now ) Surgery duration 10-13h donor 4-6h recipient 9 patients (8 Rokitanski, 1 cervical cancer) 2 graft removal 7 persistent (1 year report in fertil steril 2015 Jan) 5 livebirth to the last report (2016)