24 Prior cervical conization and uterine sparing cervical cancer surgery

Imran Hamzawala and Charlotte Chaliha

INTRODUCTION parametrial extension and lymph node metas- tasis in stage 1A1 carcinoma of the cervix is Cancer of the cervix is the second most com- less than 1%3. FIGO stage 1A2 tumors have a mon female cancer, with more than half a 7.8% incidence of nodal metastases, whereas million cases occurring annually worldwide. this increases to 16–18% with FIGO stage 1B Approximately 30% of women with cervical tumors4. The traditional treatment of cervical carcinoma are less than 35 years of age and, cancer is either radical hysterectomy or radio- for many of these women, fertility is a major therapy to the pelvis, both of which inevitably issue1. Cervical screening programs have sig- compromise fertility5. The obvious impact on nificantly reduced the incidence and death fertility of traditional surgery has led to the rates due to cervical cancer in developed introduction of techniques to preserve uter- countries with a concomitant increased rate ine function such as the radical trachelectomy. of detection of early cervical cancer accompa- However, in order to offer fertility sparing nied by a peak incidence of preinvasive disease surgery, patients must be carefully selected (cervical intraepithelial neoplasia (CIN)) at by specific examination under anesthetic and around 30 years of age2. Thus, women may careful review of available histology obtained present earlier in reproductive life with issues from previous biopsies. A magnetic resonance regarding fertility and future pregnancy which imaging (MRI) scan should be performed for could be compromised depending on the treat- careful assessment of cervical and paracervi- ment offered. Whilst the benefits of cervical cal tissues to exclude more aggressive exten- screening are regularly cited, it has not been sion of disease in order to accurately stage the implemented worldwide, and deficiencies are ­tumor6,7. particularly apparent in resource poor nations. Both the treatment of CIN and early stage Large loop excision of the transformation cervical cancer with uterine sparing surgery zone is presently the standard treatment of may have an impact on fertility and pregnancy precancerous cervical changes in those areas outcomes, and all patients seeking a fertility of the world where such technology is avail- sparing procedure must be counseled with able. Cervical conization is often used for regards to potential oncologic and obstetric superficially invasive or microinvasive carci- outcomes. This chapter discusses the current noma of the cervix (FIGO stage 1A1) in wom- fertility sparing procedures and their effect on en wanting to preserve fertility as the risk of future fertility and pregnancy.

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RADICAL TRACHELECTOMY with a gynecological oncologist for advice and follow-up during and after pregnancy. Radical trachelectomy can be performed either vaginally or abdominally depending on the surgeon’s preference and level of expertise. In Oncologic prognosis of a vaginal trachelectomy, the cervix is removed trachelectomy procedures along with parametrial tissue and a cuff of vagi- na by the vaginal route with a simultaneous Radical vaginal trachelectomy laparoscopic pelvic lymphadenectomy8,9. The uterine body is left intact and a non-absorb- A total of 790 patients have reportedly under- able suture, acting as a cervical cerclage is gone radical vaginal trachelectomy in pub- placed around the uterine isthmus to maintain lished studies which noted 4% recurrences 13 uterine competency for future pregnancies. and 2% deaths from these recurrences . These Abdominal radical trachelectomy is essen- results are comparable to those of radical hys- 14 tially a similar procedure, albeit involving an terectomies for similar sized lesions . With abdominal approach. Postoperative morbidity a tumor size of less than 20 mm and a depth with trachelectomy includes dysmenorrhea of invasion of less than 10 mm, the incidence of parametrial involvement is 0.6%15. Hence, (24%), dysplastic Pap smears (24%), irregular radical vaginal trachelectomy is reserved for or intermenstrual bleeding (17%), problems women with tumors less than 20 mm in diam- with cervical sutures (14%), excessive vagi- eter and with invasion of less than 10 mm16. nal discharge (14%), isthmic stenosis (10%), Dursun et al. in their critical literature review amenorrhea (7%) and deep dyspareunia10. of radical vaginal trachelectomies reported the Posttrachelectomy, in the absence of adverse median age as 31 years and median follow- prognostic factors, patients are advised to use up time of 48 months (1–176 months). Some contraception for 6 months before they con- 60% of patients had a diagnosis of squamous sider pregnancy to ensure that no oncological cell carcinoma and 40% had adenocarcinoma. concerns are present prior to a pregnancy11. The overall recurrence rate was reported as If prognostic factors such as positive lymph 4.2% and the death rate as 2.8%17. nodes and involved histologic margins are present, these warrant completion of treat- ment in the form of radical hysterectomy or Radical abdominal trachelectomy chemo/radiotherapy. Such additional therapy should be undertaken at a suitable postopera- Some 116 patients have undergone radical tive time which is usually 4–6 weeks postop- abdominal trachelectomy in published studies 12 eration . All trachelectomy cases require close worldwide which also report two recurrenc- gynecological oncology follow-up at 3 monthly es13. Ungar et al. reported the largest series intervals for the first year, 4 monthly intervals of 33 patients with a mean age of 30.5 years for the second year, 6 monthly intervals until (25–37 years) who underwent radical abdomi- 5 years and then yearly until 10 years. After 10 nal trachelectomy. During follow-up (median years, if no evidence of recurrence is present, 47 months), no recurrences were observed. patients should be able to return to the 3 year- These authors suggest that the radical nature ly screening program or a similar program that of the parametrial, sacrouterine, vesciocervical is acceptable to the requisite bodies of differ- and pelvic lymphatic tissue resection with the ent nations12. Consideration of pregnancy dur- abdominal approach may contribute to high ing this follow-up period should be in liaison levels of disease free survival rates18.

346 Prior cervical conization and uterine sparing cervical cancer surgery

Fertility and pregnancy outcomes ­techniques such as in vitro fertlization (IVF) postradical trachelectomy or intrauterine insemination (IUI). However, patients with infertility secondary to male Radical trachelectomy offers hope of future factor, uterine factor or unexplained factors fertility; however, posttrachelectomy, patients were less likely to conceive23. Existing data on express distress and significant concerns radical trachelectomy suggest factors such as regarding conception and pregnancy lasting cervical stenosis or adhesion formation may for up to 6 months19. Apart from the physical cause subfertility15,23 24,, as is also the case recovery from an operative intervention, the when lack of cervical mucus, subclinical sal- uncertainty of conception and the acknowl- pingitis and subclinical chronic endometritis edgment of the potential for a high-risk preg- are present24–26. nancy are obvious concerns for these patients. Given the above circumstances, it is impor- Accordingly, the immediate months postsur- tant to assess prior medical issues that may gery represent an ideal time for readdressing adversely impact future fertility. Ideally, col- potential concerns (stenosis, sexual function, laborations with fertility specialists should be reproduction) and providing referrals for developed for optimal counseling and manage- further support if needed20. The use of vagi- ment23. Boss et al., reviewing the literature, nal dilator therapy and vaginal moisturizers which included 16 studies involving 355 radi- is extremely beneficial in addressing vaginal cal trachelectomy patients, noted that 43% of stenosis, scarring and/or dyspareunia follow- patients had attempted pregnancy and that ing cancer treatment21. These modalities also 70% conceived. In those who became preg- could be beneficial in treating trachelectomy nant, 21% had a first trimester miscarriage, 8% patients with the above symptoms. Stretching had a second trimester miscarriage, 21% deliv- of tissues due to dilator therapy may reduce ered in the third trimester before 36 weeks, fibrosis and scarring if initiated early on and whereas only 50% delivered after 36 weeks27. may beneficially improve oxygenated blood In a further series, Plante et al. reported a flow to the requisite tissues22. The complex- series of 50 pregnancies in 31 patients (ret- ity of aftercare, which may vary greatly from rospective review of 72 patients treated from patient to patient, is markedly enhanced by October 1991 to October 2003) following the addition of a nurse specialist and mental fertility preserving vaginal radical trachelec- health professional to the multidisciplinary tomy. In this study, the rate of first trimester team looking after trachelectomy patients. miscarriages was similar to that of the general population (16%), as was the rate of second trimester miscarriage (4% vs 3–5%). In their Fertility and miscarriage series, 72% were able to carry their pregnan- cies to the third trimester and, of these, 78% In their summary of fertility data on patients reached term (>37 weeks). The preterm deliv- who had undergone radical trachelectomy (six ery rate was higher than in the general popula- series), Plante et al. reported an overall fertility tion (16% vs 12%)23. rate of 13% (40 of 310 patients). In this group, 14 conceived with reproductive assistance, as the adjusted fertility rate was 8% (26 of 310 Chorioamnionitis and premature patients). It was also noted that patients with rupture of membranes infertility secondary to cervical causes or ovu- latory dysfunction had a reasonable chance The increased risk of preterm delivery may be of conceiving with assisted ­reproductive related to premature rupture of membranes

347 PRECONCEPTIONAL MEDICINE secondary to chorioamnionitis as reported benefit may derive from being conservative in several series. In the series reported by with trachelectomy patients who present with ­Schlearth et al. in 2003, one pregnancy end- premature rupture of membranes, as they are ed at 22 weeks with chorioamnionitis and likely to deliver within 2–3 days and a delay another ended at 26 weeks with fetal death28. may lead to serious neonatal and maternal In another series reported by Shepherd et al., infection complications23. However, it has been six of the seven preterm births were preceded suggested in one study that expectant man- by spontaneous rupture of membranes with- agement is a reasonable option until 32–34 24 out contractions . This is similar to a series by weeks of pregnancy in patients with prema- Bernardini et al. where spontaneous rupture of ture rupture of membranes without signs of membranes occurred without contractions in ­chorioamnionitis33. four of the six premature deliveries. Expect- ant management was carried out and all four women delivered within 4 days, three showing Management of miscarriage signs of infection at the time of delivery25. The etiology of premature rupture of mem- If first trimester miscarriage occurs, expectant branes is thought to be either mechanical or management or induction with misoprostol is infectious and most probably a combination of generally successful. If necessary a dilatation both24,25,29. Shepherd et al. suggested that the and curettage can be performed under a gen- permanent cerclage placed around the isth- eral anesthetic but cervical dilatation should mus at the time of radical trachelectomy, even be kept to a minimum to reduce the risk of though buried under vaginal mucosa, may still breaking the cerclage around the isthmus23. act as a source of bacterial contamination24. The management of second trimester loss Kolomainen et al. reported a case of a postvagi- is more difficult. In the series by Plante et al. nal radical trachelectomy in a woman whose two patients spontaneously miscarried at 17 Pap smear showed presence of Actinomyces. and 20 weeks, respectively34. In the series of Since Actinomyces have been associated with Bernardini et al. the patient with second tri- chorioamnionitis resulting in preterm labor, the authors recommended that anaerobic cul- mester loss delivered after removal of cerclage 25 tures be done on pregnant patients after a radi- and induction with misoprostol . Hysteroto- cal trachelectomy either as a routine or if signs mies should be reserved for patients who fail of premature labor develop30. the expectant/medical management or show The cervical mucus plug may function to signs of sepsis. protect against ascending vaginal infection. In patients who undergo radical trachelectomy, however, disruption of endocervical glands Antenatal care results in inevitable reduction of mucus secre- tion. Thus impaired or absent production of Due to the increased risk of cervical incompe- mucus can facilitate the access of micro-organ- tence, these patients need to be followed more isms to the choriodecidual space and uterine frequently. A visit in a high-risk obstetric clinic cavity. Decidual cells, resident macrophages every 2 weeks is recommended from 18 to 28 of decidua and neutrophils initiate a cytokine weeks and weekly thereafter. If cervical incom- response. This elevation of cytokines is con- petence is diagnosed, placement of another sidered to be a cause of preterm labor and the cervical cerclage around the uterine isthmus subsequent occurrence of preterm premature should probably be attempted, depending on rupture of membranes31,32. Accordingly, little the stage of pregnancy11.

348 Prior cervical conization and uterine sparing cervical cancer surgery

Obstetricians caring for women who have Mode of delivery undergone radical trachelectomy should be familiar with the procedure and aware of In view of the permanent cerclage placed at rad- potential complications. If possible, a high- ical trachelectomy, delivery by ­cesarean ­section risk consultant with expertise in manage- is indicated. In general, cesarean sections after ment of cervical incompetence and preterm radical trachelectomy are performed via a clas- labor should take the lead in managing these sical incision in order to prevent extension of ­women. the wound44. Generally 37–38 weeks is consid- Obstetricians should also stringently aim ered an optimal time for elective delivery13. to reduce the risk of introducing infections. Hence, digital examinations should be reduced to a minimum and cervical cytology should Postnatal follow-up probably be avoided beyond the first trimes- ter23. Cessation of coitus is advisable between No data suggest that pregnancy affects the can- 20 and 36 weeks of pregnancy35. Cervical cer prognosis. Following delivery, the patient length may be followed up by serial vaginal is advised to follow-up with her routine oncol- ultrasounds36. This procedure has been used in non-trachelectomy patients where transvag- ogy appointments. inal ultrasound is found to be a good predictor of cervical incompetence with a good negative and poor positive predictive value37. CONIZATION SURGERY Although, serial fetal fibronectin has been suggested for use in the third trimester to pre- Factors affecting treatment of CIN include dict preterm birth, no data exist with regards to size and site of lesion, severity on colposcopic its use in trachelectomy patients38,39. Extrapo- examination or histology of previous biopsy, lating from the data on premature birth in the anatomical characteristics of the transforma- general population, progesterone supposito- tion zone and suspicion of glandular neoplasia ries could be considered in pregnant women or microinvasive disease45. Two types of treat- posttrachelectomy as they appear to signifi- ment are used for management of preinvasive cantly reduce preterm birth secondary to cer- disease: excisional and ablative procedures. vical incompetence in high-risk populations Excisional procedures include cold knife con- such as women with prophylactic cerclage and ization, large loop excision of the transforma- 40–42 women with previous preterm birth . tion zone and laser conization. Ablative proce- Routine prophylactic steroids to accelerate dures include laser ablation, cryotherapy and fetal lung maturity are recommended in view diathermy. of risk of premature delivery24,25. Ablation in general is used to treat small- For patients with recurrent miscarriages a er, superficial and less severe areas. Excision Saling technique was described in 1981. This treatment is used when there is a suspicion of is performed by excising and undermining the vaginal mucosa near the cervical opening, invasion, a larger area, or transformation zone stretching it over the cervix and resuturing it deep in the endocervical canal. Hence a larger in place to completely cover the cervical os to area of cervix will be removed with excisional prevent ascending infection. It is usually per- treatment. Studies show that treated women formed at 14 weeks of gestation and patency of remain at higher risk than the general popula- the cervical opening is restored at the time of tion for developing subsequent invasive cervi- cesarean section43. cal cancer, even many years after treatment46–48.

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Pregnancy outcome after Laser conization may increase the risk of pre- conization surgery term delivery51 and outcome after conization may be influenced by cone size and height52,53, A meta-analysis of 27 studies executed by Kyr- with women whose cone height is greater than giou et al. in 2006 evaluated pregnancy out- 10 mm having a higher rate of preterm ­delivery comes in women previously treated for CIN. than those with a cone height of less than This pooled analysis reported that the risk of 10 mm54. Inevitably the knife excises more tis- preterm delivery amongst women with large sue than the loop. Loop excisions that remove loop excision of transformation zone or cold large amounts of cervical tissue probably have knife conization was 1.7 and 2.6 times higher, the same effect as knife cone biopsies. Most respectively, than that of untreated women. A loop excisions in young women with fully vis- significantly increased risk was also noted for ible transformation zone need to be only 1 cm low birth weights with both methods, for pre- deep and this conservatism should protect mature rupture of membranes after large loop against serious obstetric outcomes50. excision of the transformation zone and for Transvaginal ultrasound scan can predict cesarean delivery after cold knife conization. preterm birth in women who have had large Laser ablation was not associated with adverse loop excision of the transformation zone pro- obstetric outcomes49. cedures. The negative predictive value of the In a recent meta-analysis, Arbyn et al. looked ultrasound scan is 95.2% for spontaneous at severe obstetric or neonatal outcome in preterm birth at less than 37 weeks in wom- women treated for CIN with excisional proce- en with large loop excision of transformation dures (cold knife conization, large loop excision zone55. Hence, this may be a valuable tool of transformation zone) and ablative proce- in pregnancy management along with serial dures (laser ablation, cryotherapy and diather- scans for fetal growth in view of the increased my). Criteria for severe obstetric and neonatal risk of low birth weight babies. outcome included perinatal mortality, severe (<32/34 weeks) and extreme (<28/30 weeks) preterm delivery, and severe low birth weight Mode of delivery after conization (<2000 g, <1500 g and <1000 g)50. This meta- analysis showed that cold knife conization was Vaginal delivery is not contraindicated after associated with severe adverse pregnancy out- excisional procedures on the cervix. Paraskev- comes, which included increased risk of peri- aidis et al. looked at delivery outcomes after natal mortality, severe preterm delivery and loop electrosurgical excision procedures for extreme low birth weight infants. The meta- microinvasive cervical cancer. Their study analysis by Kyrgiou et al. in 2006 had previous- showed that treated women did not have more ly suggested an increased risk of preterm deliv- delivery complications compared with con- ery and low birth weight babies was associated trols, apart from a shorter duration of labor56. with large loop excision of the transformation Another study by Klaritsch et al. looked at zone, but in the more recent meta-analysis delivery outcomes after cold knife conization large loop excision of the transformation zone of the cervix and showed that cold knife con- did not significantly affect the more serious ization is a risk factor for preterm birth and adverse obstetric outcomes; however, it was premature rupture of membranes and seems also suggested that it cannot be considered as to be a risk factor for cervical tears; however, completely free of adverse pregnancy outcome. no difference was noted in mode of delivery, Both meta-analyses showed that ablation with duration of labor, chorioamnionitis and use laser had no effect on pregnancy outcomes. of oxytocin57. In contrast, an increased risk of

350 Prior cervical conization and uterine sparing cervical cancer surgery cesarean section after cold knife excision was its high negative predictive value, it can clearly reported by Kyrgiou et al.49. identify those women who are at a low risk of residual or recurrent disease58–60. This may give more confidence to clinicians to resort to CONCLUSION less aggressive treatment practises. The intro- duction of HPV vaccine may also decrease the Cervical cancer is a disease that often affects incidence of cervical cancer and precancerous women in their reproductive years. This is lesions requiring treatment, which may sub- important, as with recent delays in childbear- sequently reduce adverse obstetric outcomes. ing in many developed countries, women may not have started their families when a diagno- sis is made. Issues regarding fertility and con- References ception therefore are highly important to them and have prompted a move from the very radi- 1. Office of National Statistics. Cancer Statistics: cal procedures of the past to fertility sparing Registration of Cancer Diagnoses 1991, England and Wales, Series MB1, no 24. London, UK: Her procedures. Majesty’s Stationery Office, 1997 Treatments such as conization of the cervix 2. Herbert A, Smith JA. Cervical intraepithe- and radical trachelectomy have shown promise lial neoplasia grade III (CINIII) and invasive with regards to future fertility and pregnancy; cervical carcinoma: the yawning gap revis- however, they are not without complications ited and the treatment of risk. Cytopathology including premature rupture of membranes 1999;10:161–70 and preterm labor, both of which may lead 3. Jones WB, Mercer GO, Lewis JL, et al. Early to significant neonatal concerns and physical invasive carcinoma of the cervix. Gynecol Oncol and emotional distress for the mother. Hence, 1993;51:26–32 4. Sevin BU, Nadji M, Averette HE, et al. Micro- patients undergoing radical trachelectomy/ invasive carcinoma of the cervix. Cancer conization, need to be thoroughly counseled 1992;70:2121–8 regarding issues of fertility sparing surgery on 5. Morrow CP, Curtin JP, Townsend DE, eds. Syn- prognosis of disease, fertility and pregnancy. opsis of Gynecologic Oncology, 4th edn. New York: It is also important to note that these patients Churchill Livingstone, 1993:111–52 need to be managed in an obstetric department 6. Peppercorn PD, Jeyarajah A, Woolas R, et al. with a high-risk obstetrics consultant special- Role of MRI imaging in the selection of patients ized in looking after such patients. Multidisci- with early cervical carcinoma for fertility-pre- serving surgery: initial experience. Radiology plinary input is essential with involvement of 1999;212:395–9 gynecological oncologist, neonatologist, nurse 7. Sahdev A, Wenaden AET, Sohaib SA, et al. specialist and mental health professional. Magnetic resonance imaging in gynaecological Ultraconservative fertility sparing surgery malignancies. Cancer Imaging 2005;5:539 for very early invasive cervical cancer (1A2 and 8. Dargent D. A new future for Schauta’s opera- early 1B1) is now under consideration. This tion through a pre-surgical retroperitoneal pel- involves a simple trachelectomy or a large cold viscopy. Eur J Gynecol Oncol 1987;8:292–6 knife cone with laparoscopic pelvic lymphade- 9. Querleu D, Leblanc E, Castelain B. Laparocop- nectomy. However, the concept of an ultracon- ic pelvic lymphadenectomy in staging of early carcinoma of the cervix. Am J Obstet Gynecol servative treatment approach warrants further 1991;164:579–81 investigation to evaluate the oncological safety 10. Alexander–Sefre F, Chee N, Spencer C, et 34 and long-term prognosis . Human papilloma al. Surgical morbidity associated with radi- virus (HPV) testing may help with the follow- cal trachelectomy and radical hysterectomy. up of women after treatment for CIN. Due to Gynecol­ Oncol 2006;101:450–4

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