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Fertility Sparing in Gynecological Cancers

Fertility Sparing in Gynecological Cancers . Fırat Ortaç, MD Güven Hospital Department of Obstetrics and Gynecology . Cancer Treatment. Objective. Adverse Effects Psychological effects Cosmetic problems Loss of organ function Sexual and reproductive dysfunction. Cure.

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Fertility Sparing in Gynecological Cancers

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  1. Fertility Sparing in Gynecological Cancers Fırat Ortaç, MD Güven Hospital Department of Obstetrics and Gynecology

  2. Cancer Treatment Objective Adverse Effects • Psychological effects • Cosmetic problems • Loss of organ function • Sexual and reproductive dysfunction Cure Fertility sparing surgery

  3. Goals of Fertility-SparingSurgery(FSS) Preservation of reproductive potential Preservation of hormonal function Preservation of healthy body image No compromise in curability

  4. FSS Objectives • Similiar oncologic outcomes to standard therapy • Favorable obstetric outcome • Benefits > risks • Low morbidity

  5. Defining prognostic factors Evidence-based Data Physician Fertility Sparing Surgery

  6. Fertility-Sparing in Gynecologic Oncology • The patient and family must be: • aware of the problem • involved in the final decision • Once the fertility has been completed, demolitive procedure should be considered

  7. Fertility-Sparing in Gynecologic Oncology • Age • Desire to preserve fertility • Tumor factors Histologic type, grade, others • Stage of disease

  8. Principles in Treatment of Early-Stage Cervical Cancer • Patient’s general status • Desire of fertility • Tumor factors • Depth and width of invasion • Size of cervical lesion • LVSI

  9. Traditional treatment of early stage cervical cancer beyond micro-invasion Radical hysterectomy + PPLND Loss of fertility

  10. LVSI Pelvik lenf nodu metastazı Pelvik rekürens Lenfadenektomi – Radikal cerrahi

  11. Spread of Cervical Cancer • Laterally (Dominant)  Parametrium • Vertically (rare) • Stage Ib and IIa  0% • Stage IIb  20%

  12. Fertility Sparing Surgery inEarly-Stage Cervical Cancer ID<3 mm LVSI(-) CONIZATION MARGIN (-) FOLLOW-UP

  13. Cold Conization

  14. CONIZATION < 10 mm Does not affect fertility potential Clin. Exp.Obstet. Gynecol, 1992: 19(1):40-2

  15. Effect of Con on Pregnancy Outcome < 15 mm NO EFFECT Frencezy A, 1995 Haffenden DK, 1993 Tan L, 2004 < 18 mm > 15 mm 25% PRETERM LABOR 18% PROM Sadler L. Et al., Am J Med Ass, 2004 > 18 mm

  16. Fertility Sparing SurgeryinEarly-Stage Cervical CancerStage Ia1 (LVS +)Stage Ia2 (LVS )Stage Ib-IIa (2cm) Desire of fertility Lymph Node Dissection (L/S, L/T) Node (+) Node (-) Sentinel Lymph Node RT RAT RVT

  17. Sentinel lymph node

  18. Radical Trachelectomy 1994 Dargent

  19. Vaginal Radical Trachelectomy (VRT)inEarly-Stage Cervical Cancar by Dargent in Lyon, France Modification of the Schauta-Stoeckel technique of vaginal radical hysterectomy Preservation of the upper endocervix and uterine corpus L/S Pelvic lymphadenectomy

  20. Radical Trachelectomy(RT)

  21. VRT-AbRT Indications • Patient who desires preservation of fertility • FIGO Stage Ia1 (+LVSI), Ia2, Ib1 • Lesions  2 cm in diameter • Limited endocervical involvement - MRI and colposcopy

  22. Surgıcal procedure • Lymph node dissection(Sentinel lymph node) • Parametrectomy • Trachelectomy (FS analyse- free margin 5-8 mm) • Cervical circlage

  23. RT Feasibility • No evidence of lymph node metastasis (Frozen section at L/S)(ultrastaging) • Upper endocervical margins free of tumor (Frozen section)

  24. VRT Results • Dargent (Lyon) 82 • Plante and Roy (Quebec) 44 • Covens (Toronto) 58 • Shepherd (London, UK) 40 • Total 224

  25. VRT Oncologic Outcome (N:24) Follow-up (months) 30 Recurrences 7(3.1%) • Parametrium 3 • Pelvic side wall1 • Distant 3 No cervico-uterine recurrence

  26. Pregnancy Results after VRT Fertil Steril 2005;84:156

  27. VRT Conclusions • Abdominal way is possible • The risk of recurrence is unchanged • Fertility is preserved • But pregnancies are at high risk • An international study is required to confirm indications and limits of this conservative technique

  28. Preserving Fertility in Endometrial Cancer 2% -14 % of endometrial cancer  40 years Up to 25% PCOS G1 Early stage Respond to progestin treatment

  29. Preserving Fertility in Endometrial Cancer Stage Ia, G1 Standart treatment TAH + BSO

  30. Preserving Fertility in Endometrial Cancer Endometrial Cancer Fertility Desire Pretreatment Evaluation Tumor Grade Depth of MI Tumor Size Hormone receptor status Flow cytometric analysis Favorable prognosis

  31. Preserving Fertility in Endometrial Cancer Inclusion Criteria • Age < 40 years • Nulliparous status • Endometrioid Carcinoma • G1 • Presence of PgR • Normal serum levels of CA 125 (<35 u/mL) and CEA (< 5 ng/mL) • Tumor DNA index < 1.3 • Absence of MI or extrauterine spread (by vaginal USG and MRI) ,surgıcal staging

  32. Pretreatment Evaluation History (infertility...) Physicial Examination TVUSG D&C Abdominopelvic/ endovajinal coil MRI Ca-125 Laparoscopic evaluation Response to Progesterone or Staging Laparotomy

  33. Preserving Fertility in Endometrial Cancer • Explain the patient the risk of conservative treatment • Evaluate the patient for prognosis • Medical treatment (Megestrol acetate 40-160 mg/d , MPA 30 mg/d  Tamoxifen 30 mg/d or GnRHa) • Repeated D&C; hysteroscopy (+tubal blockage) • No residual disease • Assisted reproduction • Elective hysterectomy when the patient no longer desires to maintain fertility

  34. Progestogenic Agents MPA 30/mg/ day Megace 40-160 /mg/day IUD / Prog Response Rate Hyperplasia with Atypia %83-94 End. Ca %57-75.6 Duration of Treatment Range 3-6 months Median 9 months Recurrens Hyperplasia with Atypia % 13 End. Ca % 11-50

  35. There is no consensus Which progesterone formulation to use What schedule to use What dose to use How long to treat How often to resample

  36. Preserving Fertility in Endometrial Cancer 72 cases in literature Positive response histologically documented 55 cases (76%)

  37. Endometrial Cancer Literature Overview (1966-2006) No pts.= 53 80% were nulliparous In 96% of them the tumor was well differentiated At least 36 pregn. were obtained by ART 70% of pts. Underwent a hysterectomy after completing gestation

  38. Uterine Leiomyosarcoma (LMS) • Diagnosis • Pre-operative? • Intra-operative frozen section? • Histopathological evaluation ofhysterectomy or myomectomyspecimen.

  39. Uterine LMS Incidence patients operated for presumed leiomyoma 0.1-0.3%

  40. Fertility Sparing Surgery inLMS • Safe margin: 3-5 mm. ? • <10 mitoses/per 10 HPF • Solitary pedinculated mass

  41. Fertility Sparing Surgery inLMS Accurately restage the patients • Color doppler USG • Hysteroscopy • Chest X-ray • MRI or CT scan

  42. Fertility Sparing SurgeryinLMS Cesarean section Multiple uterine biopsies should be taken. Delivery

  43. Fertility Sparing SurgeryinLMS • Between 1982-1996 (8 patients) • Median age: 29 • All nulliparous • Tumor was confined to myoma • Mean mitotic count 6 per 10 HPF • 3 pregnancies • Median follow-up 42 months • 7 patients alive • One patient died (26 months after diagnosis). Lissoni A (Gynecol Oncol 70(3): 348-50 (1998)

  44. Fertility Sparingin Epithelial Ovarian Cancer and Borderline Tumors

  45. Fertility Sparing Surgeryin Epithelial Ovarian Cancer and Borderline Tumors Optimal Staging: • USO or cystectomy (in BOT) • Peritoneal washing and cytology • Inspection of the contralateral ovarian surface, biopsies of any suspicious lesions Wedge resection of the opposite ovary? • Staging biopsies of the peritoneal cavity • Sampling of retroperitoneal lymph nodes or radical lymphadenectomy since 1990 • Omentectomy, appendectomy.

  46. Fertility Sparing Surgeryin Borderline Tumors • Recurrence rate in the patients underwent conservative surgery for border-line tumors is %7 Gynecol Oncol 55;552-6, 1994.

  47. Border-line Tumors of the Ovary Conservative Management and Pregnancy Outcome Cancer 1998 Jan, 1;82(1):141-6 • Retrospective review • 82 patients • 39 patients underwent conservative management • Three patients had a contralateral recurrence (7%) • 22 pregnancies were achieved.

  48. Invasive Epithelial Ovarian Cancer and Border-Line Tumors Desire for fertility Endometrial biopsy Optimal Staging FROZEN Stage Ic-III • Selected cases • Requested by patients herself • Preliminary reports. Stage Ia G1 and Border-line Stage Ia G2, G3 No further treatment Chemotherapy

  49. Can conservative surgical approach be used in selected young patients with ovarian cancer who would usually undergo radical operations. Cancer 1998 Jan, 1;82(1):141-6 • Retrospective study between 1980-1994 • 10 patients with high grade or limited extraovarian disease • Stage Ia G3 2 • Stage Ic 2 • Stage IIIa 2 • Stage IIIc 4 • All patients were given adjuvant CT • All patients were alive median follow-up 70 months • 9 patients were menstruating regularly • Three had became pregnant.

  50. Ovarian Cancer Treatment with Fertility-Sparing Therapy • Stage IA and IC epithelial ovarian cancer • 1965 to 2000, n=52 • 20 (%38) received chemotherapy • 9 (17%) eventual TAH • 5(10%) recurred, 2 died • 24 (46%) attempted, 17 (33%) conceived • 26 term, 5 SAb • 33% take home baby Schilder et al., Gynecol Oncol, 2002

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