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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

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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