Fertility-Preserving Treatments for Early-stage Cervical Cancer



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Fertility-Preserving Treatments for Early-stage Cervical Cancer

M. Roy, M. Plante and M.C. Renaud

CHUQ-Hפtel-Dieu, Universitי Laval, Quיbec, Canada

Summary

Invasive cervical cancer is classically treated with radical procedures: pelvic radiation therapy or pelvic lymphadenectomy and radical hysterectomy. In both modalities, fertility is lost. We present three new options in the management of a selected group of patients desiring conservation of fertility: Chemotherapy and conization, abdominal radical trachelectomy and vaginal radical trachelectomy. At this time, only the vaginal radical trachelectomy has shown its value regarding both aspects of oncologic and reproductive outcomes.



Introduction

Fertility preservation has been successfully attempted in some gynecologic cancers (1). Selected cases of early-stage ovarian cancers can be treated with a unilateral ovariectomy and even if chemotherapy is used, fertility is preserved in most instances. Young patients with endometrial cancers have been treated with hormonal therapy, and they were able to achieve pregnancies (2).

In early-stage cervical cancer, when pelvic lymph nodes are negative, surgical treatment gives a very good survival rate ranging between 95 to 98% (3). With such a good prognosis, loss of fertility becomes a prime concern for a young patient confronted with the diagnosis of invasive cervical cancer. However in most centers today, she is likely to be offered a radical hysterectomy as the only treatment option, with loss of fertility as a consequence.

Fertility-preserving Approaches

For FIGO stage IA1 without lympho-vascular space involvement, cold knife conization with clear margins is now accepted for women who want to keep their fertility, since the rate of parametrial and pelvic lymph node involvement is negligeable (4).

In patients with FIGO stage Ia2 disease, the risk of node metastasis goes up to 5% (5). The treatment must include pelvic lymph node dissection and parametrectomy, in order to remove all the node-bearing pelvic tissue. With today’s knowledge, conization by itself is not sufficient to accomplish this goal, since it leaves in place node bearing parametrial tissue. For stages IB1 and IIA, it is accepted that parametrectomy with pelvic lymphadenectomy is indicated.

Three fertility-preserving treatments of early-stage cervical cancer have been proposed in the last decade: Radiation therapy after pelvic lymphadenectomy and ovarian transposition, adjuvant chemotherapy with pelvic lymphadenectomy and cervical conization, and pelvic lymphadenectomy followed by radical trachelectomy, done vaginally or abdominally.



Radiation Therapy

Morice (6) has reported the experience of the Institut Gustave-Roussy in France: 26 young patients affected with cervical cancer were treated by pelvic lymphadenectomy, ovarian transposition and radiation therapy centered on the uterus and vagina. The cure rate was very good, but out of 5 pregnancies, only one live birth is reported. Castaigne, at the IGCS 2000 congress, concluded that this technique cannot then be proposed as a fertility-preserving treatment.



Adjuvant Chemotherapy and Conization

Landoni presented his experience at the IGCS meeting in Buenos Aires in 2000, as reported by Dargent (7). After a diagnosis of invasive cervical cancer, the patient is treated with chemotherapy (Taxol, Cisplatinum, Epiburicine and Ifosfamide), followed by pelvic lymphadenectomy and cervical conization. The preliminary results showed that 8 of 12 patients with 1-2cm lesions had negative nodes and no residual tumor on the cone specimen. They were followed without any other treatment. Two pregnancies with live babies occured in this group of patients.

It is still too early to draw conclusions from that small study, both regarding the risk of recurrence and the pregnancy rate, but Landoni's results are encouraging.

Radical Abdominal Trachelectomy

At the SGO meeting in 2002, Ungar (8) presented his series of 20 abdominal radical trachelectomies. The technique mimicks a radical hysterectomy, including the section of the uterine arteries, removal of the parametrium along with the cervix and a vaginal cuff, but preservation of the utero-ovarian ligaments, and reanastomosis of the uterine body with the vaginal mucosa. The authors claim that the procedure is easier that the vaginal approach pionneered by Dargent (9), but the reported complication rate (mean blood loss of 1000cc), blood transfusions (66.6%) and antibiotic use (44.4%) are much higher than with the vaginal technique. Three pregnancies are reported, but two ended in miscarriages while there is no follow up for the third. It appears that the technique is more complicated and the results are less favorable than with the vaginal approach.



Vaginal Radical Trachelectomy:

In 1987, Dargent designed a new fertility-preserving radical treatment : the vaginal radical trachelectomy (VRT) which is a modification of the Schauta-Stoeckel procedure for vaginal radical hysterectomy. The only difference is the preservation of the upper endocervix and uterine corpus.

Indications and feasability are summarized in Table 1.

Technique

The technique of VRT is well documented (10). Laparoscopic pelvic lymphadenectomy is first performed along with a laparoscopic parametrectomy. The beginning of the vaginal operation is the same as a Schauta, but after the division of the cardinal ligament, only the cervical branch of the uterine artery is ligated. The inferior part of the utero-sacral ligaments is then cut. The cardinal ligaments are sectionned and ligated 2cms away from the cervix. The uterus is divided about1cm below the isthmus which is generally very easy to identify. A frozen section for pathological evaluation of the specimen is required in order to confirm negative endocervical margins, 8 to 10mm above the cervical tumor. If the upper endocervical margins are positive for cancer, a total radical hysterectomy must be performed, because the chances of obtaining a safe margin in the upper cervix a very small. But most of the time, the upper margins are negative for cancer, and the planned operation continues by closing the peritoneum of the cul-sac using a purse-string suture. A prophylactic cerclage with a non-resorbable suture is done at the level of the isthmus. Finally the vaginal mucosa is sutured to the stroma of the cervix. A laparoscopic reevaluation of the pelvis is done after the vaginal procedure, in order to verify hemostasis.

Results


Four groups have reported their experience with VRT in the litterature (11,12,13,14). They also presented updated results at the IGCS meeting in Buenos Aires. Those results are summarized in tables 2 and 3.

Discussion

The vaginal radical trachelectomy technique described above fulfills the requirements of radical treatment of invasive cervical cancer: removal of the tumor with safe margins, pelvic lymphadenectomy, and parametrectomy. The complication rate is low, the cumulative multicenter oncologic and reproductive outcome cited above are very encouraging. We can safely affirm that the risk of recurrence for VRT is identical compared with a same group of patients treated with radical hysterectomy and that fertility is definitely preserved. It is evident though that pregnancies after VRT are high risk-pregnancies, and the delivery must be by cesarian section, because of the permanent cerclage.

Late abortion and prematurity can be major problems after a VRT. In order to avoid chorioamnionitis which is most likely responsible for premature rupture of membranes and premature labor, Dargent has proposed a complete cervical closure of the cervix during pregnancy, a technique described by Saling in 1981 for habitual abortions. In fact, in radical trachelectomy, the shortening of the cervix seems to prevent the formation of an efficacious mucus plug which is a physiological barrier between the vaginal flora and the membranes, preventing ascending infections. Data are missing to determine the value of the Saling procedure after VRT.



Conclusion

Fertility-preserving treatment of selected patients presenting an early-stage cervical cancer is possible. Of the three methods presented above, it appears that the vaginal radical trachelectomy offers the best choice in terms of feasibility and results. But larger international studies are necessary to confirm indications and limits of this conservative surgical technique.



References

  1. Plante M. New opportunities to preserve fertility in cancer treatment. J Soc Obstet Gynecol Can 24 (2):115-7, 2002.

  2. Renaud M.C. and Plante M. Medical treatment of endometrial carcinoma for the premenopausal patient wanting to preserve her ability to have children. J Soc Obstet Gynecol Can 23 (3):213-9, 2001.

  3. Kinney WK, Hodge DO, Egorshin EV et al. Identification of a low-risk subset of patients with stage Ib invasive squamous cancer of the cervix possibly suited to less radical surgical treatment. Gynecol Oncol 57 :3-6, 1995.

  4. National Institute of Health Consensus Developement Conference Statement on Cervical Cancer. Gynecol Oncol 66:351-361, 1997.

  5. Benedetti-Panici P, Maneschi F, D’Andea G et al. Early cervical carcinoma: The natural history of lymph node involvement redefined on the basis of thorough parametrectomy and giant section study. Cancer 88:2267-74, 2000.

  6. Morice P, Ba-Thiam R, Castaigne et al. Fertility results after ovarian transposition for pelvic malignancies. Hum Reprod 13:660-3, 1998.

  7. Dargent D. Fertility preserving management of early-stage cancer of the cervix. In Gynecologic Oncology Issues in the 8th IGCS Meeting. G.R.Di Paola and J Sardi eds. Monduzzi Editore, 23-30, 2000.

  8. Ungar L, Del Priore G, Boyle D.B. Abdominal Radical Trachelectomy: Follow up of the first 20 cases. Gynecol Oncol 84 (3):489, 2002.

  9. Dargent D, Brun JL, Roy M et al. Pregnancies following radical trachelectomy for invasive cervical cancer. Gynecol Oncol 52:105, 1994.

  10. Roy M and Plante M. Radical vaginal trachelectomy. In: Laparoscopic Surgery in Gynaecological Oncology. Ed : Querleu D, Dargent D, Childers JM. Blackwell Science, London, 78-82, 1999.

  11. Dargent D, Martin X, Sacchetoni A, Mathevet P. Laparoscopic Vaginal Radical Trachelectomy. Cancer 88:1877-82, 2000.

  12. Roy M, Plante M. Pregnancies after radical trachelectomy for early-stage cervical cancer. Am J Obstet Gynecol 179:1491-6, 1998.

  13. Covens A, Shaw P. Is radical trachelectomy a safe alternative to radical hysterectomy for early stage Ib carcinoma of the cervix? Cancer 86: 2273-2279, 1999.

  14. Shepherd JH, Mould T, and Oram D. Radical trachelectomy in early stage carcinoma of the cervix: outcome as judged by recurrence and fertility rate. Br J Obstet Gynaecol 108:882-85, 2001.

Table 1: Indications and feasibility for vaginal radical trachelectomy


Table 2: Oncologic outcome: N:224
Table 3: Obstetrical outcome: N: 224




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