Se ha denunciado esta presentación.
Utilizamos tu perfil de LinkedIn y tus datos de actividad para personalizar los anuncios y mostrarte publicidad más relevante. Puedes cambiar tus preferencias de publicidad en cualquier momento.

Fertility preservation in Cancer Cervix

Lecture delivered at BOGSCON 2014 (Annual Conference of Bengal Obstetric and Gynaecological Society) held at ITC SOnar, Kolkata, January, 2014

  • Sé el primero en comentar

Fertility preservation in Cancer Cervix

  1. 1. FERTILITY PRESERVATION IN CANCER CERVIX
  2. 2. Cervical Cancer • Sexual dysfunction, loss of fertility* • Reduced autonomic responses- engorgement, lubrication and orgasm • Significant dysparaeunia- due to vaginal shortening and stenosis * Bergmark K, Avall-Landqvist E, Dickman PW, Henningsohn L, Steineck G. Vaginal changes and sexuality in women with a history of cervical cancer. N Eng J Med 1999;340:1383-1389 • Surgical morbidity-  rarely severe  short-lived or at least stable  treatable  can preserve the ovarian function
  3. 3. Radical Trachelectomy • Initial tendency of small Cx tx to spread laterally into the parametria and LN, rather than verticaly into uterus/ vagina • Theoretically possible to resect cervix, parametria and lymphnodes- preserving uterus, adnexa and vagina • Like partial nephrectomy/ gastrectomy/ pneumonectomy/ colectomy • Structures removed-  Majority of the Cx  Part of parametria and paracolpos  Part of uterosacral ligament  1-2 cm of vaginal cuff  Descending cervicovaginal branch of uterine artery is ligated  Permanent encirclage of the cervical stump  Pelvic lymph nodes • Done abdominally, vaginally, laparoscopically
  4. 4. Abdominal Trachelectomy Author N Stage Estimated blood loss Complications Live Birth Recurrence Smith et al. 1997 1 IB Rodiguez et al. 2001 3 IAI-IA2 417 1 abscess 1 0 Palfalvi 2003 1 IBI 1 Del Priore et al. 2004 1 IBI Pelvic, 6 mth Ungar et al. 2005 33 IA2-IB2 6% amenorrhoea 2 0 (47 mth) Abu-Rustum et al. 2005 2 IBI 0 0 Ungar et al. 2006 91 IA2-IB2 656 4.8% amenorrhoea 6 2.4% Cibula et al. 2005 3 IA2-IBI 350-3500 1 ileus, 1 bladder atony Bader et al. 2005 1 IB1 0 1 Abu-Rustum et al. 2006 5 IBI 280 positive margin- needed completion Sx 0 0
  5. 5. Laparoscopically Assisted vaginal trachelectomy (Dargent Procedure) • 1987- Dargent described modification of Schauta- Americh radical hysterectomy to preserve uterine function* • 1st laparoscopic complete pelvic lymph node dissection- then removal of cervix along with proximal portion of parametrium * Dargent D. A new future for Schauta's operation through pre-surgical laparoscopic retroperitoneal pelviscopy. Eur J Gynecol Oncol 1987;8:292 • Plante et al- after 2 decades- oncologic outcomes are comparable to radical hysterectomy for similar sized lesions** ** Plante M, Renaud MC, Harel F, et al. Vaginal radical trachelectomy: an oncologically safe fertility-preserving surgery. An updated series of 72 cases and review of the literature. Gynecol Oncol 2004;94:614
  6. 6. Selection Criteria Eligibility criteria • Roy M, Plante M. Pregnancies after radical vaginal trachelectomy for early-stage cervical cancer. Am J Obstet Gynecol 1998;179(6):1491 1. Desire to preserve fertility 2. No clinical evidence of impaired fertility (relative C/I) 3. Lesion size ≤2.5 cm 4. FIGO stage 1A1 with LVSI, 1A2 and 1B1 5. Sq cell or adeno Ca 6. No involvement of the upper endocervical canal as determined by colposcopy/ MRI 7. No mets to regional LN • Can be done in women >40 years (reduced fertility) or those with completed family • Experience over 10 years in the Memorial Sloan-Kettering Cancer Center- 48% of women undergoing radical hysterectomy would have been candidate for trachelectomy* * Sonoda Y, Abu-Rustum NR, Gemignani ML, et al. A fertility sparing alternative to radical hysterectomy: how many patients may be eligible? Gynecol Oncol 2004;95:534-
  7. 7. * Abdominal radical trachelectomy Oncologic Outcome Authors Number Recurrences Deaths Plante and Roy 100 2 (2.0%) 1 (1.0%) Covens and Steeed 121 7 (5.8%) 4 (3.3%) Shepherd et al. 112 3 (2.7%) 2 (1.8%) Hertel et al. 100 4 (4.0%) 2 (2.0%) Dargent and Mathever 95 4 (4.2%) 3(3.1%) Ungar et al.* 91 2 (2.2%) 0 Total 619 22 (3.5%) 12 (1.9%)
  8. 8. Recurrences • Unusual recurrences- Vesico-vaginal septum and bladder- needs very meticuous surgical technique and dissection in proper plane to prevent dissemination of Tx cells * * Morice P, Dargent D, Haie-Meder C, Duvillard P, Castaigne D. First case of a centropelvic recurrence after radical trachelectomy: literature review and implications for the preoperative selection of patients. Gynecol Oncol 2004;92:1002-1005 • Recurrence in Cx itself- 2 cases 1. Bali- 7 yrs follow up (Recurrence or new primary-?) 2. Bader- 6 mnth FU- detected by Pap smear • 2 recurrences after Abd trachelectomy- both having bulky Cx (3.8 cm, 5 cm respectively) ** • Role of abd trachelectomy in bulky Cx ? ** Ungar L, Plafalvi L, Smith JR, et al. Update on and long term follow up of 91 abdominal radical trachelectomies. Gynecol Oncol 2006;101:S20(abst). • Alternative- Neo-adjuvant chemotherapy to reduce the size of the lesions- then radical trachelectomy • Experience in 3 cases- all had complete response to chemo and none had residual ds- still experimental • Plante M, Lau S, Brydon L, et al. Neoadjuvant chemotherapy followed by vaginal radical trachelectomy in bulky stage 1B1 cervical cancer: case report. Gynecol Oncol 2006;101:367
  9. 9. Follow up • Shepherd JH, Mould T, Oram DH. Radical trachelectomy in the early stage carcinoma of the cervix: outcome as judged by recurrence and fertility rates. BJOG 2001;108(8):882 • Every 3-4 months for 1st 2-3 years • Then every 6 months for next 2 years • Then every year • Colposcopy, cytology and RV examination • Colposcopy and cytology- frequently unsatisfactory because SCJ is not often visualized and cytology often meets only squamous cells • Atypical glandular cells from lower uterine segment is often picked up by cyto- false +ve results • Singh et al- 200 smears- most unsatisfactory, 2% atypical gladular cells (suspicious), only 2 cases true recurrence- abnormality long before clinical features* * Singh N, Titmuss E, Aleong JC, et al. A review of post-trachelectomy isthmic and vaginal smear cytology. Cytopathology 2004;15:97 • Shepherd- use of endoCx cytobrush for cytology and MRI 6, 12, 24 mth • Needs expert radiologists to interprete MRI** ** Sahdev A, Jones J, Shepherd JH, et al. MR imaging appearances of the female pelvis after trachelectomy. Radiographics 2005;25:41
  10. 10. Risk of recurrence • Size ≥2 cm* • LVSI* • Adeno Ca** *Plante M, Renaud M-C, Francois H, Roy M, Vaginal radical trachelectomy: an oncologic safe fertility preserving surgery. An updated series of 72 cases and review of the literature. Gynecol Oncol 2004;94:614-623 **Hertel H, Kohler C, Hillemanns P, et al. Radical vaginal trachelectomy (RVT) combined with laparoscopic pelvic lymphadenectomy: prospective multicenter study of 100 patients with early cervical cancer. Gynecol Oncol 2006:103;506-511
  11. 11. Obstetric outcomes Author Pregnancy 1st trimester loss Therapeutic abortions 2nd trimester loss 3rd trimester delivery Delivery <32 wks Delivery >32 wks Plante and Roy 59 10 (16%) 3 (4%) 2 (5%) 44 (75%) 3 (7%) 41 (93%) Dargent and Mathevet 56 11 (18%) 3 (5%) 8 (14%) 34 (61%) 5 (15%) 29 (85%) Shepherd et al. 52 15 (29%) 2 (4%) 7 (13%) 28 (54%) 7 (25%) 21 (75%) covens and Bernardini 45 8 (16%) 0 3 (7%) 34 (77%) 6 (18%) 28 (82%) Hertel et al. 14 1 (7%) 2 (14%) 0 11 (78%) 3 (27%) 8 (73%) Ungar et al. 10 4 (40%) 0 0 6 (60%) 1 (17%) 5 (83%) Total 236 49 (20%) 10 (4%) 20 (8%) 157 (66%) 25 (15%) 132 (85%)
  12. 12. Obstetric Outcomes (Contd.) • 1st trimester loss- not higher than that in general population • 2nd trimester loss- significantly higher • Prematurity <32 wk- 15% • Prematurity <28 wk (↑ morbidity) - <10% • Majority deliver at term • Prematurity rate particularly higher after multiple pregnancy in post-trachelectomy- needs special consideration before IVF-ET • Birth weight- Not significantly different as vasculat flow to uterine artery is preserved (Klemm et al. 2005) • Abdominal trachelectomy- Obst outcome similar but chance of ligating uterine arteries higher- risk of IUGR
  13. 13. Eitiology of pregnancy loss • Mechanical - uterus enlarges→ short Cx cannot offer much support to LUS→ Cx more likely to dilate prematurely • Infective- main eitiology →short Cx cannot form effective protective mucus plug between vagina and the membranes→ subclinical chorioamnionitis → PPROM and preterm labour
  14. 14. Obstetric Management • Consultation with specialist in fetal-maternal medicine • Prophylactic antibiotics and steroid to accelerate fetal lung maturity- unclear but strongly recommended by Shepherd* * Shepherd JH, Mould T, Oram DH. radical trachelectomy in early stage carcinoma of the cervix: outcome as judjed by recurrence and fertility rates. Br J Obstet Gynaecol 2001;108:882-885 • Needs USG assessment of neo-cervix (length, diameter, funneling) regularly** ** Petignat P, Stan C, Megevand E, Dergent D. Pregnancy after trachelectomy: a high risk condition of preterm delivery. Report of a case and review of the literature. Gynecol Oncol 2004;94:575-577 • Delivery should be planned at 38-39 weeks by elective CS due to permanent encerclage
  15. 15. Decision for trachelectomy • Many women, even after choosing such Sx, decide not to attempt pregnancy • Uncertain long-term survival results • There are considerable challenges to overcome • Needs pre-op counseling • In case of recurrence- total radical Sx/ RT
  16. 16. Conisation • 1A1- LEEP, Cold knife/ Laseconisation • Lymphatic spread extremely low (<1%)- no need of lymphadenectomy • Entire cone should be blocked- to prepare adequate number of sections • Needs careful colposcopic exam of vagina- as most recurrences occur from this area • 5-year survival with optimal care >95%* * Gadducci A, Sartori E, Maggino T et al. The clinical outcome of patients with stage 1a1 and 1a2 squamous cell carcinoma of the uterine cervix: a Cooperation Task Force (CTF) study. cancer J 2003;24:513-516
  17. 17. • Cone biopsy- Both diagnostic and Risk of residual disease * therapeutic • No LVSI, both endocervical margins and curettage -ve for Ca/ dysplasia • Roman LD, Felix JC, Muderspach LI, et al. Risk of residual invasive disease in women with microinvasive squamous cancer in a conisation specimen. Obstet Gynecol. 1997;90:759 • Hopkins MP. Adenocarcinoma in situ of the cervix: the margins must be clear. Gynecol Oncol. 2000;79:4-5 Conisation (Contd.) Sq Cell Ca Adeno Ca Both endocx curette and margin -ve 4% 3% Only endocx margin +ve 22% 7% Both +ve 33%
  18. 18. Management of Stage IA2 • May be individualized using non-FIGO information to stratify the patients as per H/P features  LVSI (presence/ Absence)  Degree of differentiation  Type of Tx (Adeno-/ Squamous Ca)  Tx volume (higher risk at upper limit of 1A2) • Low risk- like 1A1 • High risk- conisation + LN dissection • Radical trachelectomy + LN dissection
  19. 19. Ovarian Transposition • Transposing ovaries out of the planned RT field- if RT is required • 1st described ovarian transposition to keep the ovaries outside the radiation field* • No case of iatrogenic menopause in that series (4 cases) * Lemevel A, Bourdin S, Harousseau J, et al. Ovarian transposition by laparoscopy before radiotherapy in the treatment of Hodgkin's disease. cancer 1998;83:1420 • Bisharah and Tulandi- recommends transection of the ovarian lig and transposition of the ovaries without affecting fallopian tubes- positioning ovaries antero- laterally at the level of ASIS** ** Bisharah M, Tulandi T. Laparoscopic preservation of ovarian function: an underused procedure. Am J Obstet Gynecol 2003;188:367 • Ovarian reserve may be tested- ovarian volume, AFC, AMH, Inhibin B
  20. 20. Results • Normal ovarian function seen in <50% cases* * Fenny DD, Moore DH, Look KY, et al. The fate of the ovaries after radical hysterectomy and ovarian transposition. Gynaecol Oncol. 1995;56:3 * Anderson B, LaPolla J, Turner D, et al. Ovarian transposition in cervical cancer. Gynecol Oncol. 1993;49:206 • Risk of ovarian mets- 0.5% (sq cell Ca) and 1.7% (adenoca)- thus incurs a small risk** ** Sutton GP, Bundy BN, Delgado G, et al. Ovarian metastasis in stage IB carcinoma of the cervix: a Gynecologic Oncology Group (GOG) study. Am J Obstet Gynecol.1992;166:50 • In a series of 37 consecutive cases- clear cell adenoCa of vagina and Cx, ovarian dysgerminoma and sarcoma • Pregnancy rates in women trying for conception- 15% (4/27) for clear cell Ca of vagina/ Cx, 80% (8/10) in ovarian Tx *** ***Morice P, Thiam-Ba R, Castaige D, et al. Fertility results after ovarian transposition for pelvic malignancies treated by external irradiation and brachytherapy. Hum Reprod 1998;13:660
  21. 21. Alternatives • Oocyte retrieval • IVF and cryopreservation (ART procedure) • Cryopreservation of unfertilized oocytes- under research- low fertility rates • Autologous orthotoptic/ heterotopic transplantation after cryopreservation- can restore fertility • Ovarian tissue can tolerate ischaemia for at least 3 hours • Success depends on post-grafting ischaemia time after effective revascularization techniques • Ethics Committee of ASRM- the physician should inform the cancer survivors of the alternatives before initiation of therapy* * American Society for Reproductive Medicine. Fertility preservtion and reproduction in cancer patients. Fertil Steril 2005;83(6):1622

×