Version May 2024
INTRODUCTION — Cervical cancer is most often diagnosed in females between age 35 and 44 years [1]; thus, discussion of fertility issues, including fertility-sparing options, is an important part of pretreatment counseling. For patients who are appropriate candidates for fertility-sparing surgery and desire this approach, options may include cervical conization, simple trachelectomy, and radical trachelectomy. For those in whom fertility-sparing surgery is not an appropriate option, the psychosocial impact of cancer treatment-related infertility is significant, with a high proportion experiencing feelings of depression, grief, stress, and sexual dysfunction [2,3].
Fertility-sparing surgery for cervical cancer will be reviewed here. Additional issues related to fertility and cancer are discussed separately.
●(See "Overview of infertility and pregnancy outcome in cancer survivors".)
PREOPERATIVE ASSESSMENT AND COUNSELING
●Determine stage and histology – Procedures for staging are reviewed in detail separately. (See "Invasive cervical cancer: Staging and evaluation of lymph nodes".)
It is important to exclude the presence of lymph node metastasis [4,5]. Evidence of lymph node metastasis on preoperative imaging or at an initial staging procedure is a contraindication to performing fertility-sparing surgery. If lymph nodes appear negative on imaging, a frozen section analysis of the nodes is usually recommended at the time of fertility-sparing surgery. Surgery is aborted in favor of definitive chemoradiation if lymph node metastases are identified. An exception to performing lymph node evaluation is in patients with stage IA1 disease and no lymphovascular space invasion. (See 'Management of optimal candidates with stage IA1 cervical cancer' below and 'Timing of lymph node assessment' below.)
●Perform magnetic resonance imaging (MRI) – We consider MRI of the pelvis mandatory for all patients prior to fertility-sparing surgery because it provides precise information of tumor size and location (degree of extension into the endocervical canal, length of the endocervical canal, the distance between the upper margin of the lesion and the uterine isthmus) as well as evaluation of lymph nodes and parametrial tissues [6-9].
If the tumor appears to extend to the upper part of the endocervical canal nearing the isthmus/internal os, the likelihood of obtaining adequate free surgical margin (ie, tumor-free margin of ≥5 mm) is significantly reduced. Such patients should be informed that safe margins (≥5 mm) may not be achievable. In such cases, we prefer the option of neoadjuvant chemotherapy initially and then we proceed with trachelectomy in patients with a good clinical response (ie, a reduction of more than 50 percent of the tumor size and/or a residual lesion measuring <2 cm). Alternatively, the patient may undergo definitive hysterectomy.
●Provide reproductive counseling – Thorough preoperative reproductive counseling is mandatory to ensure that patients have realistic expectations with respect to fertility issues following radical trachelectomy [10]. In particular, patients of advanced maternal age or with known or suspected subfertility should be encouraged to seek preoperative consultation with a reproductive endocrinologist [11,12]. However, risk factors for infertility are not a contraindication to radical trachelectomy since assisted reproductive technologies can enable some subfertile patients to become pregnant [4,11,13,14].
Postoperative cervical stenosis and fallopian tube obstruction are the most common causes of infertility. Cervical stenosis is a relatively common long-term morbidity of trachelectomy and can contribute to difficulty conceiving (see 'Cervical stenosis' below). In addition to cervical stenosis, the residual cervix is shortened posttrachelectomy, which may adversely affect both fertility and pregnancy outcome. For example, in a study that systematically measured cervical length by ultrasound posttrachelectomy, patients with an active wish to conceive and a remaining cervix length <10 mm were less likely to conceive than those with a cervix ≥10 mm (6 versus 60 percent) [15]. The relationship between shortened cervical length and preterm birth is well-established. (See "Short cervix before 24 weeks: Screening and management in singleton pregnancies".)
OPTIMAL CANDIDATES FOR FERTILITY-SPARING SURGERY
Criteria — Optimal candidates for fertility-sparing surgery for cervical cancer generally meet all of the following criteria [16]:
●Desire to preserve fertility.
●Reproductive age group (the procedure is generally limited to patients <40 years old, but some patients up to age 45 years may be appropriate candidates based on their fertility potential).
●Pathologic findings consistent with a low risk for recurrent disease – Size of the lesion ≤2 cm, low-risk by HPV-related histologies, negative lymph node, and tumor-free margins ≥5 mm.
•Early-stage disease. 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IA1 through stage IB2 (table 1). However, lesions ≤2 cm (ie, stage IB1 or less) are associated with a more favorable prognosis [4,17-26]. In a systematic review including 21 case series and 1364 patients with cervical cancer who underwent vaginal radical trachelectomy (VRT), the recurrence rates among those with stage IB1 tumors ≤2 versus >2 cm in diameter were 4 and 17 percent, respectively, and 2 percent of patients with recurrent disease died [27]. In the author's series, patients with lesions >2 cm represented 10 percent of patients but accounted for 50 percent of recurrences [4].
•Squamous cell carcinoma, adenocarcinoma, and adenosquamous histology [28-30]. Although some studies suggest that patients with adenosquamous histology have a worse outcome, it is not considered an exclusion criterion [31,32]. Other histologies (eg, neuroendocrine [17-19], clear cell, carcinoid, gastric type, and other non-human papillomavirus-related rare subtypes of adenocarcinomas [25]) carry a higher risk for recurrence, so patients with these high-risk histologies are not good candidates for fertility-sparing surgery.
•Distance from tumor to the isthmus/internal os (based on preoperative magnetic resonance imaging [MRI]) should ideally be at least 1 cm to ensure a negative tumor margin of at least 5 mm on final pathology and to allow tumor-free reanastomosis [6].
•Negative lymph nodes.
In a modeling study of fertility-sparing trachelectomy, patients considered "less ideal" candidates had a fourfold higher cervical cancer recurrence rate and cancer mortality compared with "ideal" candidates (defined as lesion ≤2 cm, low-risk histology [squamous carcinoma, adenocarcinomas, and adenosquamous], no deep stromal invasion, and negative lymph nodes) [25]. Similarly, in a subsequent multi-institutional retrospective study including 733 patients with cervical cancer undergoing a fertility-sparing procedure, those with tumors >2 compared with ≤2 cm had more than a threefold higher risk of disease recurrence (19.4 versus 5.7 percent, respectively) [26].
Even with the selection criteria described above and despite a normal preoperative workup, a proportion of fertility-sparing procedures will be abandoned intraoperatively because of a positive endocervical margin or, in patients who undergo lymph node sampling as part of the fertility-sparing procedure, because positive lymph nodes are identified on frozen section. Patients with positive endocervical margins require a definitive hysterectomy (unless an additional portion of the cervix can be removed to secure the margins), while chemoradiation is usually recommended for patients with positive lymph nodes.
Selection of a fertility-sparing procedure for optimal candidates
Options — The three options for fertility-sparing surgery in patients with stage IA2 to IB1 cervical cancer, from most conservative/least morbid to least conservative/most morbid (figure 1) are:
●Conization – Resection of a cone-shaped portion of cervix.
●Simple trachelectomy – Removal of the entire cervix.
●Radical trachelectomy – Removal of the entire cervix and part of the parametrium either vaginally (VRT) or abdominally (abdominal radical trachelectomy [ART]). In most patients, VRT is preferable to ART because the vaginal approach is less morbid, but ART is indicated for some patients (eg, patients with anatomic distortion, patients in whom vaginal access would not be possible [eg, young girls], and surgeons' technical preferences). (See 'Abdominal radical trachelectomy' below.)
General principles for choosing a procedure
●The choice of procedure in stage IA2 to IB1 cervical cancer is based on trying to ensure the lowest risk for recurrence: The surgeon needs to remove a sufficiently large portion of the cervix so that the entire lesion is excised, with adequate margins and in one piece to allow adequate pathologic evaluation.
●The choice of procedure (figure 1) to achieve this goal depends on stage, lesion size, and lesion location, as well as individual surgical skills and preference. When the lesion is very small (<1 cm), conization is reasonable as long as negative margins can be achieved (see 'Conization' below). For larger lesions that are still ≤2 cm, simple or radical trachelectomy is preferable.
The probability of parametrial extension in lesions <2 cm is less than 1 percent, which is why radical surgery is probably not indicated and there is a trend toward more conservative procedures in such cases. However, given relatively little outcome data, radical trachelectomy remains the "standard of care," as the literature gradually moves toward less radical procedures that have a better obstetric outcome [33,34].
●Radical trachelectomy rather than hysterectomy is a reasonable option for patients who wish to preserve fertility because the overall rate of cervical cancer recurrence after radical trachelectomy appears to be comparable to that after radical hysterectomy for small size lesions [17,35,36]. Although data are limited, in a case-control study comparing 137 patients with tumors ≤2 cm who underwent VRT matched with controls who underwent radical hysterectomy, five-year recurrence-free survival rates were similar for both groups (95 and 100 percent, respectively) [36].
●Although radical trachelectomy is the most common fertility-sparing procedure, emerging evidence suggests conization or simple trachelectomy may be sufficient because of similar safety and efficacy for patients with lesions <2 cm [27,29,33,37-43].
Given the available data, to avoid recurrences and deaths in these highly curable patients, it is paramount that use of more conservative procedures (conization or simple trachelectomy) is accompanied by meticulous review of the preoperative pelvic MRI with an experienced MRI specialist, rigorous preoperative counseling, and a detailed pathologic evaluation of the cone or simple trachelectomy specimen by an experienced gynecologic pathologist.
In addition, one should not underestimate the seriousness of cervical cancer. Results of the prospective phase II ConCerv trial of conservative surgery for low-risk early-stage cervical cancer reported 5 percent lymph node positivity. Despite very strict study entry criteria (ie, exclusion of grade 3 adenocarcinoma, exclusion of lymphovascular space invasion (LVSI), negative margins on the cone specimen, <10 mm depth of stromal invasion), three patients (3.5 percent) developed disease recurrence and one patient had residual disease in the hysterectomy specimen [44,45].
When recurrences occur following conization, they may occur several years following treatment, and most occur on the residual cervix and thus may be salvageable. This finding confirms the importance of long-term follow-up; these cases should be managed by experienced oncologic teams and colposcopists [46,47]. Further investigation in larger studies and with long-term follow-up is needed to evaluate the oncologic safety of nonradical surgery and the fertility/obstetric benefits of less versus more radical procedures. (See 'Procedures and procedure-specific outcomes' below and 'Surgical morbidity of radical trachelectomy' below.)
Management of optimal candidates with stage IA1 cervical cancer
●Without LVSI – For patients who are optimal candidates for fertility-sparing surgery as described above (see 'Optimal candidates for fertility-sparing surgery' above) and have stage IA1 disease with no lymphovascular space invasion (LVSI; ie, tumor cells in the luminal space lined by endothelial cells), cold knife conization alone is a standard treatment approach, even in the absence of a desire for fertility preservation. No lymphadenectomy is required. (See "Management of early-stage cervical cancer".)
●With LVSI – For patients who are optimal candidates for fertility-sparing surgery as described above (see 'Optimal candidates for fertility-sparing surgery' above) and have stage IA1 disease with LVSI, VRT is the most commonly performed procedure worldwide. However, we suggest more conservative surgery (conization or simple trachelectomy) as a reasonable option in patients with negative lymph nodes, and this approach is becoming more prevalent.
It is difficult to determine precisely how LVSI affects outcome since many studies have not reported this feature specifically. In a systematic review, among 473 patients for whom details were available, the rates of recurrence after radical trachelectomy were as follows: positive LVSI (14 patients; 7 percent recurred) and negative LVSI (311 patients; 5 percent recurred) [27].
Although LVSI has been implicated as an independent prognostic factor for recurrence [17], primarily nodal recurrence, in our experience and that of others, LVSI alone is not an absolute contraindication to radical trachelectomy [18,19,48]. The main factors affecting local/cervical recurrence appear to be related to the status of the surgical margins and depth of stromal invasion. However, given the uncertainty, patients with LVSI should be informed of the potentially higher risk of recurrence, particularly when LVSI is extensive [27,49,50].
Management of optimal candidates with stages IA2 and IB1 cervical cancer — For patients who are optimal candidates for fertility-sparing surgery as described above (see 'Optimal candidates for fertility-sparing surgery' above) and have stage IA2 or IB1 disease, radical trachelectomy is the most commonly performed procedure worldwide. However, a trend toward more conservative surgery is emerging. (See 'General principles for choosing a procedure' above.)
Postsurgical indications for additional treatment
Inadequate margins — Occasionally, margins appear adequate on frozen section but are close (<5 mm) on final pathology, possibly because of tissue retraction after fixation [51]. In most of these cases, we resect an additional portion of cervix to secure adequate margins or perform a definitive hysterectomy if adequate resection is not technically feasible. Alternatively, very careful, conservative follow-up may be offered to patients who understand and accept the potentially higher risk of local recurrence with this approach [4,16].
High risk factors (Peters criteria) — Patients are at high risk for recurrence if they have any of the following on final pathology:
●Positive surgical margins
●Pathologically confirmed involvement of the pelvic lymph nodes
●Involvement of the parametrium
Adjuvant chemoradiation is usually recommended for these patients. However, in the case of positive surgical margins, after careful discussion and if technically possible, an additional portion of cervix may be removed to ensure negative margins. (See "Management of early-stage cervical cancer", section on 'High-risk disease'.)
Intermediate risk factors (Sedlis criteria) — Patients are at intermediate risk for recurrence if they have any of the following on final pathology:
●LVSI plus deep one-third cervical stromal invasion and tumor of any size
●LVSI plus middle one-third stromal invasion and tumor size >2 cm
●LVSI plus superficial one-third stromal invasion and tumor size >5 cm
●No LVSI but deep or middle one-third stromal invasion and tumor size >4 cm
In general, adjuvant radiation therapy is recommended in these cases. However, careful, individualized discussion is required, weighing the potential higher risk of local recurrence against the permanent loss of fertility after pelvic radiation. Ovarian transposition or egg harvesting can be discussed and offered to patients prior to radiation therapy. A definitive hysterectomy can also be offered after careful, individualized discussion, although patients should be informed that adjuvant radiation therapy may still be indicated according to the final pathology of the hysterectomy specimen. (See "Management of early-stage cervical cancer", section on 'Intermediate-risk disease' and "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)
APPROACH TO FERTILITY PRESERVATION IN NONOPTIMAL CANDIDATES (LESION SIZE >2 CM)
Options — There is consistent evidence that lesion size >2 cm is associated with a higher risk for recurrence following radical trachelectomy and is the strongest risk factor for recurrence [21-24,26,27,32,52,53] (see 'General principles for choosing a procedure' above). Patients who would be optimal candidates for fertility-sparing surgery but have a lesion >2 cm have two therapeutic options:
●Neoadjuvant chemotherapy (NACT) followed by fertility-sparing surgery in good responders
or
●Upfront abdominal radical trachelectomy (ART)
Neoadjuvant chemotherapy followed by fertility-sparing surgery — NACT is administered to reduce tumor size, making it possible for good responders to become candidates for fertility-sparing surgery [54-57]. Overall, it is estimated that over 70 percent of patients will have a good response to NACT (ie, residual tumor measuring ≤2 cm following NACT, based on clinical examination and pelvic magnetic resonance imaging [MRI] postchemotherapy) [58]. Our preference is to perform lymph node evaluation first and then, in histologically node-negative patients, we suggest NACT over ART because NACT followed by fertility-sparing surgery seems to offer a greater chance of fertility preservation and better obstetric outcome compared with upfront ART. (See 'Upfront abdominal radical trachelectomy' below.)
NACT followed by fertility-sparing surgery has also been reported in patients with even larger lesions. In a systematic review of 11 observational studies including 40 patients with stage IB3 (ie, >4 cm) cervical cancer, successful fertility preservation surgery was achieved in 26 patients (65 percent) [59]. A complete or partial pathological response to NACT was noted in 56 and 44 percent of patients, respectively. Of the six patients who tried to conceive, four (67 percent) achieved at least one pregnancy during the 55-month (median) follow-up period; preterm birth occurred in 60 percent of these pregnancies (all of whom had a radical trachelectomy). Although interesting, these results are based on a small number of patients. More data are needed to ensure the safety of this approach in patients with IB3 lesions and, thus, it should be considered experimental at this time.
A suboptimal chemotherapy response (ie, residual lesion >2 cm following NACT) is a surrogate marker for poorer outcome [60,61]. We believe such patients should undergo definitive treatment, either radical hysterectomy, primary radiation, or chemoradiation. (See "Management of early-stage cervical cancer", section on 'Primary therapy' and "Management of locally advanced cervical cancer", section on 'Neoadjuvant chemotherapy'.)
A number of issues remain unsettled: timing of lymph node assessment in relation to the NACT, the optimal NACT regimen, and the type of fertility-sparing surgery. (See 'Preoperative assessment and counseling' above and 'NACT regimen' below and 'Extent of fertility-sparing surgery post-NACT' below.)
Timing of lymph node assessment — The timing of lymph node assessment is controversial; it may be performed as part of the initial staging procedure (ie, prior to NACT) or at the time of the fertility-sparing procedure (ie, after NACT).
We prefer the first option so as to exclude patients from NACT who are definitely node positive, given that node positivity is a marker of poorer outcome. These patients are upstaged to stage IIIC1 (table 1) and are generally treated with chemoradiation.
The disadvantage of this approach is that some patients with minimal lymph node involvement, which might have cleared completely with NACT, will be excluded from consideration for fertility-sparing surgery. In a study comparing upfront radical hysterectomy versus NACT followed by radical hysterectomy in patients with stage IB2 to IIA2 disease, the rates of lymph node metastasis in the two groups were 25.6 and 8.1 percent, respectively, suggesting that NACT has the potential to eradicate cancer cells in lymph nodes [60]. This issue is controversial, and at this point, it appears more prudent not to offer fertility-sparing surgery to node-positive patients.
Other investigators prefer to administer NACT first and then perform the lymph node evaluation at the time of the fertility-sparing surgery, recognizing that patients found to be node positive will require adjuvant treatment [62].
NACT regimen — Cisplatin and paclitaxel (TP) used to be the preferred NACT regimen. Earlier studies on NACT followed by fertility-sparing surgery have used the cisplatin, ifosfamide, and paclitaxel (TIP) regimen [52]. TIP is very effective but more hematologically toxic and gonadotoxic than TP, so many oncologists have eliminated ifosfamide from the regimen [63,64].
However, there is a trend toward replacing cisplatin with carboplatin because of its ease of administration and overall lower toxicity. In a systematic review of 17 studies with 1181 patients with recurrent or metastatic cervical cancer, carboplatin appeared to be similarly effective and less toxic than cisplatin [65]. A randomized trial in patients with locally advanced cervical cancer (Japan Clinical Oncology Group [JCOG] 0505) reported similar findings [66].
Another trend is toward using a dose-dense paclitaxel-carboplatin regimen, which has a response rate ranging from 68 to 87 percent in locally advanced cervical cancer [67]. However, neoadjuvant dose-dense paclitaxel-carboplatin prior to fertility-sparing surgery has been reported in only one study with apparent good response [68]. An even higher rate of response (92 percent) to NACT (the majority with cisplatin-based regimens) was reported in one systematic review; disease recurrence occurred in approximately 6 percent of patients and of the 64 patients who became pregnant, over two-thirds experienced favorable obstetric outcomes [69].
Following NACT, size of the residual lesion on imaging appears to correlate well with the pathological size on trachelectomy specimen [70]. This emphasizes the importance of MRI evaluation following NACT to assess tumor response and properly select patients with good response to fertility sparing surgery.
Extent of fertility-sparing surgery post-NACT — It is unclear if a radical trachelectomy is required following NACT or whether a simple trachelectomy or even a large conization is sufficient. In patients with a complete clinical response to NACT, a normal clinical examination, and normal pelvic MRI, there is probably a very low likelihood of finding occult parametrial infiltration; therefore, a radical procedure may not be necessary, but there is no clear consensus on this issue, and further studies are needed. Based on limited available data [27,29,33,37-42], we perform a large conization or simple trachelectomy in optimal chemoresponders since less radical surgery is associated with better obstetric outcome compared with more radical surgery [71].
An international prospective phase II trial is currently underway to evaluate the option of NACT followed by fertility-sparing surgery, with primary outcomes being the preservation of a functional uterus and three-year progression-free survival [58]. Results of this trial should provide robust data as to the feasibility and safety of this approach and provide data on oncologic outcome, fertility preservation, and quality of life.
Upfront abdominal radical trachelectomy — ART, rather than vaginal radical trachelectomy (VRT), is typically performed in patients with lesions >2 cm because more extensive parametrial resection is generally obtained with ART and desirable in these higher risk cases.
A major downside of upfront ART is the substantial probability that positive nodes (which occur in 10 to 15 percent of cases of lesions measuring 2 to 4 cm), positive margins or parametrium (Peters criteria), or intermediate risk factors (Sedlis criteria) will be identified on final pathology of the surgical specimens, necessitating adjuvant treatment. A series of 333 ART procedures (132 with lesions >2 cm) reported that up to 48 percent of patients required adjuvant treatment because of unfavorable pathologic findings [32]. In most centers, adjuvant chemoradiation is recommended, which would result in both infertility and premature ovarian failure in this young patient population. Adjuvant chemotherapy alone is a promising alternative to chemoradiation as it would allow fertility preservation, but it remains investigational [72].
Even if fertility is not compromised, pregnancies following ART are associated with higher rates of obstetric complications, such as preterm labor, premature rupture of membranes, and preterm birth compared with pregnancies following NACT/fertility-sparing surgery (eg, preterm birth after ART: 57 percent; after NACT/fertility-sparing surgery: 15 percent [71]). In a 2019 systematic review comparing rates of fertility, pregnancy, and oncologic outcomes for patients with stage IB2 cervical cancer with lesions measuring ≥2 and <4 cm who underwent either upfront ART or NACT followed by VRT, NACT/VRT was associated with better obstetric outcomes without worsening oncologic outcomes (table 2) [73]. More recent studies have not reported better pregnancy rates: 7 and 17 percent for ART [73,74] and 21 percent for NACT/fertility-sparing surgery [73]. Furthermore, a subsequent literature review suggested a higher recurrence rate following NACT with conservative surgery and better outcomes following upfront radical trachelectomy [75].
PROCEDURES AND PROCEDURE-SPECIFIC OUTCOMES
Intraoperative frozen section of cervical tissue — If no grossly visible cervical lesion is present, we proceed with fertility-sparing surgery and keep the trachelectomy/cone specimen intact for final pathologic analysis.
If a grossly visible cervical lesion is present at the time of fertility-sparing surgery or we have concern about the status of the margin after excision, we send the specimen for frozen section [51,76]. The evaluation of the frozen section is of key importance as results correlate accurately with the final pathology [77]. The pathologist is asked to perform the frozen section longitudinally (from the exocervix to the endocervix) at the level of the lesion in order to determine the distance between the superior endocervical tumor margin and the specimen excision margin. Ideally, the margin of normal tissue above the cancer should be 8 to 10 mm, but 5 mm is acceptable. If the margin is less than 5 mm, and if technically possible, an additional slice of cervix should be removed.
If excision of more cervix is technically not possible, then we would recommend a definitive hysterectomy. For patients who decline hysterectomy but are candidates for fertility-sparing surgery except for a margin less than 5 mm, fertility-sparing surgery can still be performed with the understanding that the risk for local recurrence may be higher and close follow-up is particularly important.
Conization
●Procedure – Cold knife conization is the resection of a cone-shaped portion of the cervix using a scalpel. A description of the procedure can be found separately. (See "Cervical intraepithelial neoplasia: Diagnostic excisional procedures", section on 'Cold knife conization'.)
●Oncologic outcome – In a systematic review, conization was performed in 347 cases of early-stage cervical cancer (IA1 and IB1) and was associated with a recurrence rate of 0.4 percent (95% CI 0-1.4) and a death rate of 0 percent (95% CI 0-0), which was similar to the rate in patients who underwent radical trachelectomy [37]. In a subsequent systematic review including over 649 patients from 23 observational studies, recurrence rate after simple trachelectomy or conization was 4.1 percent; one death was reported [75].
●Pregnancy outcome – Conization and simple trachelectomy seem to result in better pregnancy outcomes than radical trachelectomy, most likely because less cervical tissue is removed [33,37,71,78].
Simple trachelectomy
●Procedure – A simple trachelectomy is performed transvaginally and involves the removal of most of the cervix in a "cylinder" shape as opposed to a "cone" shape (as for conization) (figure 1).
We begin the procedure by infiltrating the exocervix with a solution of xylocaine and epinephrine and begin the incision at the cervicovaginal junction to allow the removal of the entire exocervix. The bladder is then mobilized anteriorly, and the vaginal mucosa is mobilized posteriorly. The anterior and posterior cul-de-sac are usually not entered. The uterine vessels are not ligated (only the descending cervical/vaginal branches). The cervix is then amputated with a cold knife to avoid cauterization artifacts and sent to pathology.
If the lesion extends toward the vaginal fornix, we remove a rim of vaginal mucosa along with the trachelectomy specimen (as we do for radical trachelectomy) to ensure negative lateral margins.
An endocervical curettage is always performed afterward.
To close, we reapproximate the vaginal mucosa to the residual cervix with interrupted sutures. The decision to place a cerclage is individualized and depends on the amount of residual cervix left following the procedure.
●Oncologic outcome – In a series of 50 patients with early-stage, low-risk cervical cancer who underwent a simple vaginal trachelectomy/conization with laparoscopic sentinel lymph node mapping with or without complete pelvic node dissection, one patient had a recurrence and subsequently died of the disease [33]. In another series of 40 patients undergoing conization with laparoscopic lymphadenectomy, one patient had a recurrence in the remaining cervix, and no patients died [34]. Previous studies also found that the risk of parametrial infiltration with nonradical surgery was low (<1 percent) in patients like the optimal candidates described above (see 'Optimal candidates for fertility-sparing surgery' above) and probably does not justify the morbidity of radical surgery [38,41,79-82]. Moreover, in patients who underwent diagnostic conization, studies have shown that up to 62 to 67 percent of early-stage, low-risk patients do not have any residual cancer in the radical trachelectomy specimen [17,19,83]. Therefore, a simple trachelectomy or a large cold knife conization is probably sufficient resection for these patients.
●Pregnancy outcome – Conization and simple trachelectomy seem to result in better pregnancy outcomes than radical trachelectomy, most likely because less cervical tissue is removed [33,37,71,78].
Radical trachelectomy
Choice of approach — The radical trachelectomy procedure can be performed vaginally, abdominally, laparoscopically, or robotically. The vaginal and laparoscopic approaches should be limited to patients with lesions <2 cm as the risk of recurrence is increased in patients with larger lesions. In our practice, we use a vaginal approach for optimal candidates (see 'Optimal candidates for fertility-sparing surgery' above). Others may choose an abdominal or minimally invasive surgical (MIS) approach based on their surgical skills, preferences, and access to equipment. A 2020 systematic review concluded that, although the literature is limited to case series and reports, oncologic outcomes, such as recurrence rate, death from disease, recurrence-free survival, and overall survival, are favorable, with no significant difference between the surgical approaches [84]. However, pregnancy rates and obstetric outcome appear to be superior following the vaginal approach (table 3).
The main advantage of the abdominal approach compared with the vaginal approach is a shorter learning curve without the need to acquire skills in laparoscopic and vaginal surgery nor acquire special instrumentation or training. Worldwide, the abdominal surgical approach is probably the most commonly used surgical approach, for the following reasons:
●Implementation in resource-limited countries appears to be easier, safe, and feasible [85].
●Wider parametrium can be obtained via the abdominal route compared with the vaginal approach, and as such, the procedure can be offered to patients with larger size lesions [86].
●It is technically easier and possible in patients with anatomic distortion and those in whom vaginal access would not be possible (eg, young girls) [87].
Disadvantages include the need for a midline laparotomy incision, greater blood loss, longer hospital stay, and sacrifice of the uterine arteries bilaterally, which may cause endometrial atrophy and cervical stenosis/scarring as well as low birth weight in future pregnancies [88]. Although improvements in the surgical technique now allow for uterine artery preservation in most cases [89,90], one study using computed tomography angiography suggested that the benefit is limited because 87.5 percent of patients had occlusion of the uterine arteries [91].
The MIS approaches, laparoscopic radical trachelectomy and robot-assisted radical trachelectomy, have the advantages of avoiding abdominal incisions and appear to have lower surgical morbidity, but concerns have been raised regarding poorer oncologic outcomes.
In an international retrospective study including 646 patients with early-stage cervical cancer (ie, tumor size ≤2 cm), those undergoing open abdominal (358 patients) compared with MIS (288 patients) radical trachelectomy had similar recurrence rates and disease-free survival, however recurrence rates were overall low [92]. There were six disease-related deaths (three in the abdominal group and three in the MIS group) during the 4.5-year study period.
Conventional approaches
Vaginal radical trachelectomy
●Procedure – The vaginal radical trachelectomy (VRT) procedure involves an en bloc resection of the cervix along with 1 to 2 cm of vaginal mucosa and proximal parametrial tissue. We then place a permanent cerclage just superior to the margin with a 1-0 nonresorbable polypropylene suture, forming a neocervix, which is resutured to the vaginal mucosa. Some surgeons prefer Mersilene tape for the cerclage [93], but we feel it increases the chances of erosion and infection.
●Oncologic outcome – Summary data from 1491 cases of cervical cancer managed by VRT showed the following pooled rates: recurrence (3.8 percent) and death from disease (1.7 percent) (table 3) [94].
Approximately 40 percent of recurrences occur in the parametrium or pelvic sidewall, possibly due to insufficient parametrial excision or to the presence of microscopic lymphovascular space invasion [95]. Twenty-five percent of recurrences occur in the pelvic, paraaortic, and supraclavicular lymph nodes [18]. Use of sentinel node mapping may help identify potentially missed nodal micrometastasis and aberrant lymph node draining sites, which may explain some of these nodal recurrences [5,18].
Five centropelvic recurrences have been reported; four of these were in patients with adenocarcinomas and may have been due to the multifocal nature of this type of lesion [94].
●Fertility and pregnancy outcomes – The reported incidence of infertility following VRT ranges widely from 14 to 41 percent [4,13,78]. Post-VRT, cervical factors account for 40 to 75 percent of fertility issues, with the remainder due to causes unrelated to the surgery [4,78,93,96].
Pregnancy after radical trachelectomy and cerclage is associated with favorable obstetric outcomes for the majority of patients; summary data are shown in the table (table 3) [71,84,97]. The rate of first-trimester miscarriage following radical trachelectomy is comparable to the rate in the general population (10 to 20 percent) [13,19,53,98,99]. The rate of second-trimester miscarriage following VRT ranges from 3 to 19 percent, which is higher than that in the general population (approximately 2 percent) [4,13,19,53,94,97,98]. Cervical factors after trachelectomy may predispose the patient to development of cervical insufficiency and/or chorioamnionitis and subsequent pregnancy loss. The risk for an individual patient likely depends on how much cervical tissue was conserved.
The rate of preterm birth is increased after radical trachelectomy and can reach 50 percent or more [71,78,98,100]. In our practice, the preterm delivery rate is 4 percent for 24 to <32 weeks of gestation and 14 percent for 32 to <37 weeks [4]. We believe that our low preterm birth rate is probably due to our technique of preserving at least 1 cm of endocervix at trachelectomy rather than excising the entire cervix; this provides some support of the lower uterine segment and did not increase the risk of local cancer recurrence in our patients [88]. Another institution, which also uses a VRT technique of transecting the cervix approximately 1 cm from the internal os, reported a preterm delivery rate of 5 percent for <28 weeks of gestation and 25 percent for 28 to 36 weeks [94,97].
As with second-trimester miscarriage, the increased risk for preterm birth may involve mechanical factors (the uterus puts too much pressure on the short cervix, causing it to open prematurely) and/or infectious factors (impaired endocervical mucus plug does not provide adequate barrier against ascending infection), resulting in preterm labor and/or preterm prelabor rupture of membranes (PPROM) [78].
In patients with a cerclage, it is unclear if the cerclage itself may increase the risk of intrauterine infection from ascending vaginal flora, thus increasing the risk of PPROM [98].
Abdominal radical trachelectomy
●Procedure – Abdominal radical trachelectomy (ART) is usually performed through a midline incision. The paravesical and pararectal spaces are developed, the round ligaments are divided, and then the uterine vessels are divided at their origin from the hypogastric vessels. Care is taken to preserve intact the infundibulopelvic and tubo-ovarian ligaments as they will constitute the main source of vascular supply to the uterus. The parametria and paracolpos, along with the uterine vessels, are mobilized with the trachelectomy specimen. A complete ureteral dissection through the parametrial tunnel is required as in a type III radical hysterectomy procedure. The posterior cul-de-sac is incised, and the uterosacral ligaments are divided.
The required length of vaginectomy is then resected circumferentially via an anterior colpotomy, and the specimen is completely separated from the vagina distally. This may be facilitated by the use of a vaginal cylinder to help delineate the vagina. Proximally, the specimen is excised approximately 5 mm below the internal os and is sent for frozen section analysis. If margins are secure, a permanent cerclage is placed abdominally circumferentially at the level of the isthmus, although some authors do not place any cerclage at all. The uterine fundus, along with the preserved utero-ovarian ligaments, is inspected for signs of ischemia. Lastly, the lower uterine segment is reanastomosed to the vaginal apex with six to eight interrupted absorbable sutures.
●Oncologic outcome – Pooled summary data from 955 patients with cervical cancer managed by ART showed a recurrence rate of 3.3 percent and death from disease in 1.5 percent of patients (table 3) [94].
●Fertility and pregnancy outcome – Infertility is more likely to occur after ART than VRT [19,71]. Nevertheless, in one study in which 38 patients attempted to become pregnant after ART, 28 (74 percent) were successful [53]. A subsequent literature review confirmed that although oncologic outcome are very good, ART is associated with lower fertility rates and is associated with more severe surgical complications [75]. (See 'Upfront abdominal radical trachelectomy' above.)
Pregnancy after radical trachelectomy and cerclage is associated with favorable obstetric outcomes for the majority of patients [71,84,97]. The rate of first-trimester miscarriage following radical trachelectomy is comparable to the rate in the general population (10 to 20 percent) [13,19,53,98,99]. Summary data for pregnancy outcome are shown in the table (table 3).
Minimally invasive surgery — MIS trachelectomy refers to conventional laparoscopic trachelectomy or robot-assisted trachelectomy. Data from retrospective studies show similar recurrence and survival rates for MIS and abdominal approaches [92,101]. In the large international retrospective study discussed above (see 'Choice of approach' above), those undergoing a laparoscopic (121 patients) compared with robotic (167 patients) approach also had similar recurrence rates (7.4 versus 5.4 percent, respectively) [92].
However, more data are needed to confirm the safety of MIS in the surgical management of early-stage cervical cancer. Adherence to strict surgical principles during MIS to avoid contaminating the peritoneal cavity with tumor cells from the cervix is of paramount importance to ensure good oncologic outcomes [102]. For example, avoiding the use of a uterine manipulator and performing transvaginal closure of the vaginal cuff can reduce the risk of tumor spillage.
Procedure-specific information is provided below.
Laparoscopic radical trachelectomy
●Procedure – The laparoscopic approach requires advanced laparoscopic skills but appears to be effective with low morbidity when performed in centers with appropriate experience of laparoscopic techniques [11,17,18,83]. A detailed description of the procedure is beyond the scope of this review.
●Oncologic outcome – Data regarding oncologic outcomes are conflicting. Summary data from 120 cases of cervical cancer managed by laparoscopic radical trachelectomy showed no recurrences or deaths from disease, however, this is was likely related to the small number of cases (table 3) [94]. In the large international retrospective study discussed above (see 'Minimally invasive surgery' above), recurrence and death rates were higher, but overall rates were still low [92].
Patients with larger tumors may have worse oncologic outcomes. In a series including 79 patients with cervical cancer undergoing laparoscopic trachelectomy, those with tumor size >2 cm compared with ≤2 cm had higher recurrence rates (20.7 versus 6 percent, respectively) [22]. These data support our recommendation to limit this surgical approach to patients with small-volume disease (ie, <2 cm). (See 'Choice of approach' above.)
●Reproductive outcome – Data on obstetric outcome with MIS procedures are limited [15,22,103,104]. Summary data are shown in the table (table 3) [84].
Robotic radical trachelectomy
●Procedure – The robotic approach offers the radicality of the abdominal approach with the benefits of an MIS approach. The technique is similar to the abdominal technique; a detailed description of the procedure is beyond the scope of this review. Uterine artery preservation and nerve-sparing techniques have also been described [105].
●Oncologic outcome – Although data are limited, results appear promising [15,19,92,106]. Oncologic results appear to be comparable to open and laparoscopic procedures, morbidity is low, blood loss is minimal, and hospital stay is very short. However, one group reported conversion to radical hysterectomy in 4 of 12 patients because of inadequate clearing of the endocervical surgical margin, possibly because of difficulty palpating or feeling precisely the lower uterine segment, thus making it more difficult to determine where to amputate the cervix in relation to the level of the tumor [106].
●Reproductive outcome – Data on obstetric outcome with MIS procedures are limited [15,22,103,104].
SURGICAL MORBIDITY OF RADICAL TRACHELECTOMY
Overview — Complications are common posttrachelectomy (reported by up to 74 percent of patients surveyed), with cervical stenosis being the most common [12]. Perioperative morbidity of radical trachelectomy is the same or less than that for radical hysterectomy [11,17,18,83,107]. Morbidity includes symptoms due to the retained uterus and cerclage placement (eg, vaginal discharge, irregular bleeding, dysmenorrhea, amenorrhea, cerclage erosion), symptoms related to scarring of the vaginal vault (eg, deep dyspareunia), and symptoms related to cervical stenosis. The complications of cerclage are discussed in detail separately. (See "Transvaginal cervical cerclage" and "Transabdominal and laparoscopic cervicoisthmic cerclage".)
Morbidity appears to be higher after abdominal radical trachelectomy (ART) than vaginal radical trachelectomy (VRT) [53,100,108,109]. Short-term morbidity includes greater blood loss and higher infection rates. The increased long-term morbidity of ART may be related to its radical nature, whereby uterine artery ligation and damage to the ovarian/uterine vasculature leads to ovarian failure, cervical stenosis, and Asherman syndrome. Extensive parametrial excision during ART can also impair fallopian tube motility/function or cause obstruction and is associated with fertility problems. Unique complications following ART have been reported, such as uterovaginal anastomosis dehiscence and uterine necrosis [74].
Cervical stenosis — Cervical stenosis is a relatively common long-term morbidity. In a systematic review including 1547 posttrachelectomy patients, the mean incidence was 10.5 percent (0 to 73.3 percent) [110]. Among patients with ART, VRT, laparoscopic, and robotic radical trachelectomy, the incidences of cervical stenosis were 11.0, 8.1, 9.3, and 0 percent, respectively. Placement of an intrauterine device at the time of trachelectomy may be effective in preventing this problem [111].
Although the stenosis is often asymptomatic, some patients develop dysmenorrhea, hematometra, hematosalpinx, or endometriosis [112]. Others may have infertility and difficulty with transcervical procedures, such as those used for assisted reproduction [96,112-114].
Managing cervical stenosis may be challenging posttrachelectomy, and a variety of approaches have been proposed to help manage the problem [115]. Standard approaches to management of cervical stenosis (eg, dilation) may be applied, but stenosis tends to reoccur over time. Care should be taken in women who have had a trachelectomy since anatomic changes occur after surgery (eg, the exact position of the neocervix can be difficult to find) [111,116]. In some cases, cannulation may be necessary under general anesthesia and under ultrasound guidance. We have performed a small loop electrosurgical excision procedure under general anesthesia to open the cervical os, then placed a pediatric Foley catheter (8F) in the uterine cavity followed by intrauterine insemination. Three patients successfully conceived after the procedure.
POSTTREATMENT SURVEILLANCE — There are no definitive guidelines for follow-up of patients after fertility-sparing surgery. We suggest:
●Long-term follow-up by experienced oncologic teams as the majority of recurrences occur on the residual cervix. Most of these can be salvaged with curative intent [46,47].
●Cervical cytology and human papillomavirus (HPV) co-testing and a colposcopic examination (with or without endocervical curettage) every three to four months for the first three years, every six months for the next two years, and yearly thereafter [117]. However, practice varies, and longer intervals (eg, 12 months) between testing in selected patients (eg, those with two consecutive negative high-risk HPV tests and absence of high-grade cytology) have been described; the incidence of recurrent disease in such patients is low (<1 percent) [118].
Patients who remain HPV positive following the trachelectomy procedure or who are reinfected are at higher risk of cancer recurrence.
Cytology evaluation posttrachelectomy is challenging as it is often obtained from the lower uterine segment, which may lead to false-positive interpretation. The cytology, thus, needs to be carefully interpreted by an experienced cytologist. Follow-up cervical cytology after trachelectomy frequently shows abnormal results. A thorough colposcopic evaluation of patients with abnormal cervical cytology and communication with an experienced cytopathologist are critical to avoid unnecessary evaluation of benign smears [83].
In a review of 197 Pap tests following vaginal radical trachelectomy, 2 percent were false-positive results (most often due to atypical endometrial cells) and up to 41 percent of smears contained only squamous cells [119]. In a few cases, cytology identified recurrences long before the recurrences became clinically apparent [119]. By contrast, in another study, cytology did not contribute significantly to the diagnosis of cancer recurrence [120].
●HPV vaccination of unvaccinated patients to reduce the risk of future reinfection and to reduce the risk of cancer recurrence in the remaining cervix. (See "Human papillomavirus vaccination".)
Although we do not routinely obtain follow-up imaging, some experts advocate follow-up pelvic magnetic resonance imaging at 6, 12, and 24 months [117]. These should be read by radiologists familiar with patients who have undergone radical trachelectomy since some of the anatomic changes secondary to the procedure may be misinterpreted as cancer recurrence [121].
MANAGEMENT OF INFERTILITY AND PREGNANCY
Infertility — Patients with infertility after cervical surgery should be evaluated for cervical factors as well as other etiologies (including evaluation of a male partner), as appropriate. (See "Overview of infertility".)
Pregnancy planning and management
●Following excisional procedures – Patients treated with an excisional procedure (eg, cold knife conization) are at an increased risk of preterm birth (PTB) and its sequelae.
In one population-based study evaluating obstetric outcomes after fertility-sparing surgery for early-stage cervical cancer, patients with stage I cervical cancer treated with an excisional procedure (ie, cold knife conization, loop electrosurgical excision procedure) compared with population controls experienced higher rates of PTB before 37 weeks (21.5 versus 9.3 percent, odds ratio [OR] 2.7, 95% CI 1.4-5.1); the rate was also higher than cervical cancer controls (ie, patients diagnosed with cervical cancer after delivery; 21.5 versus 12.7 percent, OR 1.9, 95% CI 1.0-3.6) [122]. Preterm birth rates before 32 weeks were similar between groups. In a subsequent cohort study including patients with early-stage cervical cancer treated with conization or simple trachelectomy, preterm birth before 37 weeks occurred in 19 of 58 (32 percent) cases; three of these births (16 percent) occurred before 28 0/7 weeks of gestation [123]. Five patients experienced pregnancy loss. Patients were advised to wait six months after the fertility-sparing procedure before attempting to conceive; cerclage was not used in any of the patients and use of progesterone was not reported.
Other reproductive effects following excisional procedures are discussed in detail separately. (See "Reproductive effects of cervical excisional and ablative procedures", section on 'Adverse reproductive effects of procedures performed before pregnancy'.)
●Following radical trachelectomy – Patients should be informed that pregnancies following radical trachelectomy are also associated with a higher risk of complications, and for this reason, a specialist in maternal-fetal medicine should be involved in their care [124].
We suggest that patients wait at least 6, and preferably 12, months following radical trachelectomy before attempting to conceive [99].
There is limited evidence upon which to base recommendations on the management of these pregnancies. Information from studies on preterm labor and preterm prelabor rupture of membranes (PPROM) in patients whose primary diagnosis is cervical insufficiency has been extrapolated to this population [88]; there are no data from randomized trials directly addressing management of patients after radical trachelectomy. A variety of interventions have been proposed, including routine screening for genital tract infection, prophylactic antibiotics, bed rest and/or reduced physical activity, and routine administration of glucocorticoids to hasten fetal lung maturation in the event of a preterm delivery [78]. However, there is no evidence to support these as prophylactic measures in this patient population. We and others do not advise patients to reduce physical activity during pregnancy unless there are signs of cervical shortening. Given the increased risk of second-trimester pregnancy loss and preterm birth, we follow patients closely and suggest monitoring cervical length with serial ultrasound examinations [98,99,125] and administering antenatal glucocorticoids when indicated. (See "Short cervix before 24 weeks: Screening and management in singleton pregnancies" and "Cervical insufficiency" and "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)
We do not administer prophylactic antibiotics to prolong pregnancy in patients with intact fetal membranes. Randomized trials in patients at high risk of preterm birth have shown that broad spectrum antibiotic therapy administered to asymptomatic patients with intact membranes does not prevent preterm labor or birth.
If PPROM occurs, delivery is recommended if there is evidence of chorioamnionitis or the pregnancy is at least 32 to 34 weeks of gestation. In the absence of these findings, the cerclage is left in place, and prophylactic antibiotics are administered during expectant management. Management of PPROM is discussed in detail separately. (See "Preterm prelabor rupture of membranes: Clinical manifestations and diagnosis" and "Transvaginal cervical cerclage", section on 'Removal of cerclage after PPROM'.)
Management of fetal demise — In patients who have a fetal demise (or fetal anomaly) following trachelectomy and cerclage placement, the cerclage does not usually prevent expulsion of the products of conception in the first and early second trimester. If spontaneous expulsion does not occur with expectant management, misoprostol can be given to stimulate contractions [99,126]. If medical management is unsuccessful, dilation and curettage is another option. In these cases, the cervix should be dilated just enough to allow passage of the suction cannula. Some clinicians use laminaria to facilitate dilation [126].
Alternatively, particularly for late second- or third-trimester fetal demise, some surgeons prefer to remove the cerclage and then induce labor with misoprostol [93]. If the cerclage has to be removed, another cerclage can be placed at the time of a subsequent pregnancy, ideally at 12 to 14 weeks of gestation. An abdominal cerclage may be required if the cervix is too short or scarred after the trachelectomy [127].
Hysterotomy is rarely required to accomplish pregnancy termination [20]. (See "Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial evaluation" and "Second-trimester pregnancy termination: Induction (medication) termination" and "Overview of second-trimester pregnancy termination".)
Route of delivery
●For patients who underwent conization or simple vaginal trachelectomy, vaginal birth is reasonable in the absence of usual indications for cesarean delivery and in the absence of a cerclage.
●For patients who underwent radical trachelectomy, we recommend cesarean delivery, which we perform at 37+0 to 38+6 weeks of gestation. We usually make a low transverse incision; others favor a low vertical incision in view of the potential risk of lateral extension into the uterine vessels, but this risk is very low [83,117]. Vaginal delivery should be avoided because a lateral cervical tear in the short, scarred cervix may extend into the nearby uterine vessels, resulting in catastrophic hemorrhage.
We suggest not performing cesarean hysterectomy unless there are special circumstances, but others offer this procedure at the time of the last delivery for patients who have completed childbearing [20].
HYSTERECTOMY WHEN CHILDBEARING IS COMPLETE — The decision to perform hysterectomy after childbearing has been completed is a matter of debate as no data are available comparing long-term outcome with versus without the procedure. We and other experts do not routinely recommend hysterectomy [19,83] but discuss the procedure with patients to offer individualized recommendations. We do advise definitive hysterectomy in patients who remain positive for human papillomavirus once childbearing is complete. Some patients, such as those with abnormal uterine bleeding or unsatisfactory Pap tests because of cervical stenosis, may choose to have a definitive hysterectomy.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment of cervical cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Cervical cancer (The Basics)")
●Beyond the Basics topics (see "Patient education: Fertility preservation in early-stage cervical cancer (Beyond the Basics)" and "Patient education: Cervical cancer treatment; early-stage cancer (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Preoperative assessment and counseling – Preservation of fertility is a major issue for reproductive-age cancer patients. Before selecting a treatment strategy, preliminary staging and magnetic resonance imaging (MRI) of the pelvis are required to define the extent of disease, particularly in patients with a visible lesion, and assess whether the patient is a candidate for fertility-sparing surgery. Thorough preoperative reproductive counseling is also required to ensure that patients have realistic expectations with respect to fertility issues. (See 'Introduction' above and 'Preoperative assessment and counseling' above.)
●Management of optimal candidates – Before performing ultraconservative procedures in patients with early-stage cervical cancer, a careful and thorough evaluation by an experienced gynecologic oncologist is essential. In addition to a preoperative pelvic MRI, careful pathology review of the diagnostic loop electrosurgical excision procedure or cone by an experienced gynecologic pathologist is essential. (See 'General principles for choosing a procedure' above.)
•For patients with stage IA1 cervical cancer without lymphovascular space invasion (LVSI) and who have no evidence of intermediate- or high-risk features (eg, histologies other than squamous carcinoma or adenocarcinoma), cervical cold knife conization alone is a standard treatment approach regardless of fertility concerns. Lymphadenectomy is not required. (See 'Management of optimal candidates with stage IA1 cervical cancer' above.)
•For patients with stage IA1 cervical cancer with LVSI and negative lymph nodes, we suggest conservative surgery (conization or simple trachelectomy) rather than radical trachelectomy (Grade 2C). Patients with LVSI who undergo conservative surgery should be informed of the potentially higher risk of recurrence, particularly when LVSI is extensive. (See 'Management of optimal candidates with stage IA1 cervical cancer' above.)
•For patients with stage IA2 or IB1 disease who are optimal candidates for fertility-sparing surgery, the choice of procedure is based on trying to ensure the lowest risk for recurrence: The surgeon needs to remove a sufficiently large portion of the cervix so that the entire lesion is excised, with adequate margins and in one piece to allow adequate pathologic evaluation. The choice of procedure (figure 1) to achieve this goal depends on stage, lesion size, and lesion location, as well as individual surgical skills and preference.
We suggest large cold knife conization rather than trachelectomy when the lesion is very small (<1 cm) (Grade 2C), as long as negative margins can be achieved. For patients with larger lesions that are still ≤2 cm, simple or radical trachelectomy is preferred.
The risk of parametrial extension appears to be very low in patients with small-volume, low-risk disease. The morbidity of less radical surgery is lower, and obstetric outcomes are better. More data are needed to confirm safety and long-term oncologic outcomes, but available data suggest outcome to be comparable to that of more radical surgery. (See 'General principles for choosing a procedure' above and 'Management of optimal candidates with stages IA2 and IB1 cervical cancer' above.)
•Postsurgical indications for additional treatment include inadequate margins and/or presence of intermediate- or high-risk criteria for recurrence. (See 'Postsurgical indications for additional treatment' above.)
●Management of nonoptimal candidates – Patients who would be optimal candidates for fertility-sparing surgery but with a lesion >2 cm have two therapeutic options: neoadjuvant chemotherapy (NACT) followed by fertility-sparing surgery in good chemotherapy responders or upfront abdominal radical trachelectomy (ART). We exclude lymph node involvement first, and then, for histologically node-negative patients, we suggest NACT followed by fertility-sparing surgery over ART (Grade 2C). NACT followed by large conization or simple trachelectomy seems to offer a greater chance of fertility preservation and better obstetric outcome compared with upfront ART (table 2). (See 'Approach to fertility preservation in nonoptimal candidates (lesion size >2 cm)' above.)
A suboptimal chemotherapy response (ie, residual lesion >2 cm following NACT) is a surrogate marker for poorer outcome. For these patients, we suggest definitive treatment: radical hysterectomy, primary radiation, or chemoradiation (Grade 2C). (See 'Neoadjuvant chemotherapy followed by fertility-sparing surgery' above.)
●Role of cerclage – A permanent cervical cerclage is usually placed following radical trachelectomy. A cerclage may be omitted following simple trachelectomy or conization. (See 'Procedures and procedure-specific outcomes' above.)
●Complications – Complications are common following trachelectomy (reported by up to 74 percent of patients surveyed); cervical stenosis is the most common complication. (See 'Surgical morbidity of radical trachelectomy' above.)
●Outcomes – Oncologic and pregnancy outcomes are shown in the table (table 3). (See 'Procedures and procedure-specific outcomes' above.)
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