Our case-control study shows that NSRAT appears safe and effective with regard to fertility preservation in women with early-stage cervical cancer. Local recurrence rate and overall survival and disease-free survival do not differ significantly after NSRAT and NSRH in our cohorts (Table 3). Moreover, site of recurrence does not differ between both groups. The non–statistically significant difference in overall recurrence rate (7.4% and 14.3% after NSRAT and NSRH, respectively) is, however, remarkable and may be due to selection, although the number of high-risk patients did not differ significantly between both cohorts. Our data implicate that, although numbers are small, NSRAT is safe in women with early-stage cervical cancer who wish to preserve fertility. Pregnancy rate is as high as 53% (95% CI, 28.7%–77.2%), indicating that NSRAT is effective in preserving fertility. Literature on abdominal trachelectomy is scarce, but our survival rates and pregnancy rates seem to be similar to those reported by others.12,13,22,23 A recent literature review by Pareja et al24 looking at surgical, oncological, and obstetrical outcomes shows that abdominal radical trachelectomy is a safe option for patients with early-stage cervical cancer.
Other recent studies have shown results of surgical treatment for early-stage cervical cancer by RVT in combination with pelvic lymphadenectomy with regard to fertility preservation.10,25–27 These reports show that RVT is performed mostly in small cancers. For example, in the large series on VRT recently published by Speiser et al,27 the median tumor size is microscopic, whereas in our series the median tumor size at histological examination after surgery is 13.5 mm (mean, 17.3; range, 0.1–38 mm; Table 2). Because parametrial involvement is extremely rare in tumors less than 20 mm, especially in the absence of lymphovascular space infiltration (LVSI), one can argue whether these patients need a parametrectomy at all.28 In women with small tumors (ie, <20 mm), an excisional cone or simple trachelectomy with pelvic lymphadenectomy has shown excellent survival and low recurrence rates, although the median follow-up was only 16 months.29,30 These data indicate that we may end up performing excisional cones in the low-risk patients (small tumor <20 mm in diameter without LVSI) and NSRAT in the higher-risk patients (larger tumors, with LVSI) with early-stage cervical cancer who wish to preserve fertility.
Because of small numbers, we could not differentiate the risk of recurrence for high- and low-risk women. As mentioned above, there is much debate about the need for parametrial resection and whether parametrial resection is in the detection of local spread or nodal spread. In this respect, it is important to compare the presence of nodes in the parametrium after (type 2) RVT and conventional RH: 8% versus greater than 90% of specimen.26 ,31 Hence, if nodal spread is considered an issue, RVT may leave a significant percentage of nodes undetected, especially if sentinel node detection is not performed.
Apart from tumor size, another important reason to prefer the abdominal approach above the vaginal route to perform a trachelectomy is the possibility of selectively sparing the autonomic nerves in the pelvis, as this is technically not possible in vaginal trachelectomy. Although there are, to our knowledge, no data on autonomic nerve damage after radical trachelectomy, there is abundant evidence that the pelvic autonomic nerves are damaged during RH.32 This damage is thought to be the leading cause of the well-known long-term bladder, bowel, and sexual morbidity after conventional RH.2 Because there is solid evidence that nerve-sparing surgery reduces these complications,13 ,33,34 it seems more than logic to adopt nerve-sparing surgery in radical trachelectomy, especially because nerve-sparing surgery is considered safe and feasible in early-stage cervical cancer.7 ,35 Nerve-sparing was successful in the vast majority of both our patients and control subjects (89.3% and 96.1%, respectively). However, from the analysis of the dysfunctions, possibly due to nerve damage, it can be concluded that failed nerve-sparing surgery does not inevitably lead to dysfunction, nor will nerve-sparing surgery fully prevent dysfunctions. Clearly, autonomic function does not mimic autonomic nerve damage as suggested in our recent longitudinal in-depth analysis of bladder, bowel, and sexual function after conventional RH and NSRH.36
The main risk factors for recurrence of cervical cancer are tumor size more than 20 mm, stromal invasion of more than 10 mm, and presence of LVSI.28 Our cases were treated with neoadjuvant chemotherapy if tumors were 40 mm or more in their largest diameter on histological examination. Others have proposed neoadjuvant chemotherapy for bulky cervical cancers in women who wish to preserve fertility as well: it is suggested to decrease the number of positive nodes, and it reduces tumor volume before surgery, permitting less radical and hence more successful fertility-preserving surgical techniques.37,38 Although not much has been published about the use of neoadjuvant chemotherapy in fertility preservation, the data on its use in cervical cancer are abundant, and this protocol is considered safe and effective.39,40 Although small, our series adds data to support the use of neoadjuvant chemotherapy mainly because it does not hamper fertility preservation.
As the aim of the radical trachelectomy is to preserve fertility, it is also important to consider the condition and functionality of the uterus after surgery with regard to possible pregnancies. Because of cervical incompetence (both mechanical and with regard to prevention of infection), second-trimester abortion and premature delivery are the main concerns after trachelectomy.23 Because the uterine arteries are ligated in conventional trachelectomy, the blood supply to the uterine corpus may be reduced. Collateral circulation from the utero-ovarian ligaments is considered to keep the uterine tissue viable, but it is thought to provide reduced blood supply to the corpus leading to decreased fertility, less placental function, and consequently probably a higher risk of premature rupture of membranes and premature labour.30 As described in detail, our technique allows specific sparing of the ascending branch of the uterine artery, resulting in better blood supply to the uterine corpus during pregnancy. This uterine artery–sparing technique is used by others as well.14 In our opinion, the fact that none of our cases had either second-trimester abortion or fetal growth retardation may have been in relation to the sparing of the ascending branches of the uterine artery.
In this study, 2 experienced gynecologic oncologists have performed all surgeries. We have collected 28 cases for NSRAT in a period of a little more than 10 years. Incorporating our technique into one’s clinic armamentarium needs consideration of the learning curve and experience, which are needed for achieving good results. Moreover, with the interpretation of our results, we have to take the small sample size and observational design of our study into account. Both may have led to bias. For example, women with nonfavorable characteristics may have been counseled to non–fertility-preserving treatment. Moreover, we had to include a lower-than-intended number of control subjects. Although post hoc comparison of both groups does not show any differences with regard to the well-known risk factors for local recurrence, and data were collected prospectively, the previously mentioned methodological weaknesses need to be taken into account and incorporated into counseling respective women.
This study demonstrates that NSRAT results in recurrence and survival rates that do not differ from those after conventional treatment (NSRH) in women with early-stage cervical cancer. The overall pregnancy rate after NSRAT was 53%. There was no fetal loss or premature delivery in our series. In our opinion, NSRAT is feasible and safe and should be offered to women with early-stage cervical cancer who want to preserve their fertility. In women with larger tumors, neoadjuvant chemotherapy can be administered to down-stage the tumor and allow for fertility-sparing surgery. In both situations, we have to bear in mind that the level of evidence of our study is moderate. That is why treating gynecologic-oncologists are obliged to give full and detailed information, and both counseling and treatment should be centralized to gain and maintain experience.
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Keywords:© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.
Cervical cancer; Fertility preservation; Radical surgery; Pregnancy; Survival; Neoadjuvant chemotherapy