1. Francesco Fanfani Gynecologic Oncology Dpt. Obstetrics & Gynecology Catholic University - Rome francesco.fanfani@rm.unicatt.it Radical trachelectomy in patients who wish to conceive

2. Actual fertility-sparing treatments at Catholic University – Rome, Italy Operative ISC+HT Conization plus LPS LFN ± CT Borderline tumors Early stage Borderline tumors Early stage

3. The 2nd most frequent cancer in European young women IARC, 1999. EU, female (age 15–49) New cancers: 106,906 28% of all and 39% of stage I are <40 years old Definite trend toward deferral of childbearing into the late 30s and early 40s has been documented. A higher and higher proportion of patients will be diagnosed with CC before having started or completed their childbearing program

5. FERTILITY PRESERVATION APPROACHES: WHICH? Radical trachelectomy Vaginal (RVT) Abdominal (RAT) Laparoscopic RVT Laparoscopic RAT Neo-adjuvant CT + RT Neoadjuvant CT + conization

6. General inclusion criteria: Detailed informed consent Age < 40 years Strong desire to retain fertility No clinical evidence of impaired fertility Stage IA1 with LVSI – IB1 No small-cell neuroendocrine carcinoma Tumor volume < 2 cm (Colposcopy/US/MRI) Stroma infiltration < 50% No pelvic/aortic nodes (CT or PET-CT)

8. Intraoperative assessment: No extra-uterine spread No lymph node or SLNs metastasis Adequate margin of healty stroma assured Frozen section

10. RADICAL TRACHELECTOMY: A LITTLE HISTORY RADICAL TRACHELECTOMY: A LITTLE HISTORY First description of “colpohisterectomia largita subfundica” for microcarcinoma and in situ cervical carcinoma Aburel, ’32,’73,’81 Development of Radical Vaginal Trachelectomy (RVT) Dargent, ‘94 Radical Abdominal Trachelectomy (RAT) is popularized Smith, ’97 RAT with ligation of the uterine arteries Rodriguez, ’01 Total laparoscopic radical trachelectomy proposed as an alternative approach Cibula, ‘05

13. Rob L. et al Lancet Oncol 2010

14. Fertility outcome in early CC pts undergoing RVT undergoing RVT Only 40% of women administered fertility preservation procedure attempts to conceive Need to psycho-physically recover from surgery No partner at time of study Other not addressed reasons THE ABANDONMENT OF FERTILITY IS WORTH FURTHER CAREFUL INVESTIGATION

15. In 25-30% of cases attempting to conceive infertility is found Infertility status was already known prior to fertility preserving surgery In case of post-surgical infertility: 75% related to the “cervical factor”: absence of cervical mucus cervical stenosis :15% 12% related to anovulation 12% idiopathic (subclinical salpingitis?) Patients should be evaluated for their fertility status before surgery Should infertility be a contra-indication to fertility preserving surgery? - Cases of spontaneous pregnancy -Role of ART Fertility outcome in early CC pts undergoing RVT undergoing RVT

16. Trachelectomy ( 700 cases since1994) Obstetrical results Oncological results Obstetrical results Safety Early miscarriages: 20% Tardive miscarriages: 10% pPROM + Pre-term deliveries: 30% Gien et al, Gyn Onc 2010

18. Maneo 16 pts FIGO stage IA2-IB1. Landoni Follow up69 months Relapses0 Obstetric follow up 9/16 pts planned to conceive Miscarriage1 spontaneous (first trimester) Spontaneous deliveries at term 2 (1 pt) Casarean sections7 Prophylactic cerclage 7 (first trimester) 11 pts FIGO stage IA2-IB1. Follow up20 months Relapses0 Obstetric follow up 3/6 pts planned to conceive Miscarriage0 Spontaneous deliveries at term 3 Casarean sections 0 Prophylactic cerclage 0

19. This was a prospective single-institution study, including consecutive patients with early-stage CC (FIGO stages IA2– IB1).

20. Inclusion Criteria 1.Tumoral volume ≤ 20 mm 2.No previous CT and/or RT. 3.No preoperative suspicious lymph nodes. 4. Age ≤ 45 years. 5. FIGO stage IA2-IB1.

22. Follow up20 months (12-111) Recurrence0 Follow up5/13 pts (40%) tried to conceive Miscarriage/CT0 Deliveries (no preterm)2 (40%) [2 pts] FIVET3 (60%), no pregnancy Cervical cerclage0

23. 37 IB1 CC submitted to simple conization + pelvic LFN Median tumor 11.7 mm (8-25) Follow up 66 months (6-168) 1 (2.7%) pelvic lymph node recurrence 22 pregnancies, in 17 pts (45.9%) and 14 live babies 2 (5.4%) preterm deliveries (27-32 w) 3 (8.1%) first trimester miscarriages, 1 (2.7%) second trimester, 1 (2.7%) GEU. 5 (13.5%) wanted hysterectomy (after 3-12 ys); 1 residual microinvasive adenocarcinoma was found

24. UCSC algorithm fo early stage CC desiring FS surgery LPS removal of pelvic lymphatic center frozen section -ve+ve RHCold knife conization -ve margin/nodes+ve nodes+ve margin -ve nodes FU Adjuvant Therapy

25. UCSC ongoing trials  Chemo-conization for FIGO stage IB1-IIA1 larger than 2 cm.  SLN in FIGO stage IB1-IIA1 smaller or equal to 2 cm.  Prospective avaluation of QoL after cone biopsy with respect to trachelectomy

26. Take home messages Early stage cervical women should be counseled about the possibilities of a fertility-sparing management. Early stage cervical women should be counseled about the possibilities of a fertility-sparing management. Strict inclusion criteria have to be applied. Strict inclusion criteria have to be applied. Management of young women with early gynecologic cancer should therefore be individualized with the risk of conservative therapy balanced against the dangers and advantages of more radical therapy. Management of young women with early gynecologic cancer should therefore be individualized with the risk of conservative therapy balanced against the dangers and advantages of more radical therapy. The field of oncofertility requires therefore a multidisciplinary approach which should include a specialized team. The field of oncofertility requires therefore a multidisciplinary approach which should include a specialized team.

27. Thank you for your attention