9. Surgical treatment – Cervical Carcinoma

A wide variety of principles and techniques in surgical treatment have developed during the last 20 years alongside the therapeutic standard for the treatment of patients with cervical carcinoma (Fig. 6). These are presented in Chapter 8. Unfortunately, therefore, there are wide variations in treatment in Germany, with results that are not comparable, and without the individual treatment procedures being confirmed by larger randomized controlled studies. This is ultimately to the detriment of patients, for whom universal access to standardized, stage-dependent and thus comparable therapy of proven efficacy should be available — therapy that can be expected to benefit them.

The aim is therefore to define the stage-dependent standard treatment. Deviations from it and modifications of it must be explained to the patient, and the advantages and disadvantages (e.g., morbidity, the physician’s own experience and training) must be discussed with her critically.

Various principles and combinations of them are available (preserving fertility, nerve-sparing treatment, compartment resection/total mesometrial resection [TMMR], supraradical surgery). There are also various distinct surgical techniques, such as conization (scalpel conization, laser conization, high-frequency loop electrosurgical excision procedure [LEEP]), cervical amputation (simple cervicectomy), radical cervicectomy, simple total hysterectomy, radical hysterectomy, and various extended techniques (e.g., laterally extended endopelvic resection [LEER], exenteration).

The aim in surgical treatment for early cervical carcinoma is to avoid multimodal therapies — i.e., to avoid adjuvant radiochemotherapy or adjuvant surgery and to keep morbidity low. This goal is particularly served by the nerve-sparing therapeutic approach of total mesometrial resection (TMMR). Very promising survival data have been reported in a prospective single-center study including more than 500 patients [317], [318]. An open multicenter observational study will clarify whether the excellent survival data can be confirmed on a multicenter basis.

The access route for these techniques also has to be decided on (abdominal, vaginal, laparoscopic, robot-assisted), as well as the lymphadenectomy technique (diagnostic sentinel technique, diagnostic surgical staging, therapeutic pelvic and para-aortic lymphadenectomy). These principles and techniques overlap in several areas (see Fig. 6).

The phase III study published in 2018, which randomly assigned 631 patients with FIGO IA1–IB1 cervical cancer either to one arm with laparoscopic radical hysterectomy (including robotic surgery) or another with abdominal open radical hysterectomy, provided the guideline group with the first randomized controlled trial concerned with the surgical approach for these tumor stages. The study did not identify any non-inferiority of microsurgery vs. open surgery in relation to the disease-free survival could be shown: 96.5% vs. 860 % (95% CI, −16.4 to −4.7; P = 0.87 for non-inferiority). In relation to overall survival after 3 years, open hysterectomy was also significantly superior to laparoscopic hysterectomy: 99.0% vs. 93.8% (hazard ratio [HR]: 6.00; 95% CI, 1.77 to 20.30).

This is in contrast to the current figures from the Eighth Oncology Quality Conference in 2020, for which tumor center data for 43,091 patients from 11 federal states in Germany were retrospectively evaluated for the period 2000–2018. One of the items evaluated was surgical treatment: minimally invasive vs. open surgery. Minimally invasive operations increased over time regardless of age and stage. Vaginal hysterectomy was the main access route used, accounting for almost 60% of cases. In contrast to internationally published prospective data, this evaluation demonstrated the superiority of minimally invasive surgical techniques in relation to overall survival, independently of the disease stage (HR 1.494; 95% CI, 1.334 to 1.673; P < 0.0001) [25]. In view of the much stronger significance level, the guideline group has followed the RCT.

The classic surgical technique is radical hysterectomy, which is carried out in a stage-dependent manner on the basis of the 1974 classification by Piver et al. [301], in accordance with the recommendations by Wertheim, Meigs, Latzko, Okabayashi and others (see Fig. 6 and the classification of radical hysterectomy).

The basic principles of the radical abdominal operation involve the following steps. The procedure in laparoscopic or robot-supported methods is analogous.

• Opening of the abdominal cavity, systematic inspection.
• In premenopausal women, the ovaries may be retained.
• Opening of the paravesical fossa. If there is a suspicion of involvement of the ureterovesical junction, a quick-section examination is carried out. If there is tumor involvement, the operation is stopped. Additional options include partial bladder resection or exenteration.
• Incision into the Douglas peritoneum and opening of the pararectal fossa; removal of connective and adipose tissue with the lymphatic vessels and nodes (see section 8.1.1.3).
• Demonstration and removal of the parametria in a stage-dependent manner, with a sufficient safety margin to the tumor (see the classification of radical hysterectomy).
• Mobilization of the rectum and removal of the sacrouterine ligaments.
• Complete dissection of the ureter from the parametria.
• Mobilization of the ureter after dissection of the bladder pillar.
• Removal of the paracolpium and vagina, depending on the size of the primary tumor and extent of vaginal involvement; the aim is to achieve an adequate vaginal safety margin.
• Closure of the abdominal wall.

The Piver classification distinguishes between five degrees of radicality in the hysterectomy [301]:

Removal of the uterine tubes does not have any negative effects on ovarian function [343], [344], but may reduce the risk of an ovarian or tubal carcinoma developing [345] [346]. Estimates show that the rate of high-grade serous ovarian carcinomas could be reduced by 40% over the next 20 years if both fallopian tubes were removed during hysterectomy [346]. This procedure also does not appear to be associated with increased morbidity for the patient [347]. This additional measure and its potential benefits should therefore be discussed with the patient on an individual basis.

In the largest study dealing with squamous cell cervical carcinoma (n = 3471), the incidence of ovarian metastases relative to stage was 0.22% (Ib), 0.75% (IIa), and 2.2% (IIb). For adenocarcinoma, the rates were 3.72% (Ib), 5.26% (IIa), and 9.85% (IIb). Overall, ovarian metastases are found much more often with adenocarcinoma in comparison with squamous cell carcinoma: 5.31% vs. 0.79% [348]. The guideline group therefore recommends adnexectomy for all postmenopausal patients starting from stage IB1 and in premenopausal patients with adenocarcinoma in stages IB2, IIA2, and IIB (see recommendations 8.14 and 8.15).

In a large multicenter phase III trial published in 2018, 631 patients with FIGO IA1–IB1 cervical cancer were randomly assigned to either laparoscopic radical hysterectomy (including robotic surgery) or abdominal open radical hysterectomy. The primary outcome measure was disease-free survival after 4.5 years and non-inferiority of the minimally invasive group. Secondary outcome measures were the recurrence rate and overall survival after 3 years. No non-inferiority of microsurgery vs. open surgery was found in relation to disease-free survival: 96.5 % vs. 86.0% (95% CI, −16.4 to −4.7; P = 0.87 for non-inferiority). In relation to overall survival after 3 years, open hysterectomy was also significantly superior to laparoscopic hysterectomy: 99.0% vs. 93.8% (HR 6.00; 95% CI, 1.77 to 20.30). The rate of intraoperative and postoperative complications was the same in both arms. For the subgroups of low-risk tumors < 2 cm, without lymphatic invasion, with a depth of invasion of < 10 mm, or negative lymph nodes, no conclusions could be drawn [349]. The Uterus Committee of the Working Group on Gynecologic Oncology (AGO) and the Working Group on Gynecologic Endoscopy (AGE) of the German Society for Gynecology and Obstetrics (DGGG) have stated that patients with FIGO IA1 cervical carcinoma with lymphatic invasion, IA2, or IB1 should be informed about the results of this study before a decision is taken on the planned access route for radical hysterectomy when it is indicated [350].

In a cohort study from the USA, also published in 2018, 1225 patients (FIGO IA2–IB1) who had undergone laparoscopic surgery were compared with 1236 patients who had undergone abdominal incision surgery. After a median follow-up period of 45 months, the 4-year mortality rate was 9.1% after laparoscopic hysterectomy and only 5.3% after open hysterectomy (HR 1.65; 95% CI, 1.22 to 2.22; P = 0.002 in log-rank test). A longitudinal analysis showed that the 4-year survival rate had decreased by 0.8% (95% CI, 0.3–1.4) per year (P = 0.01) since the introduction of laparoscopic hysterectomy in 2006 [351].

Similar results were obtained in another cohort study including 958 patients (475 with open abdominal surgery and 483 with minimally invasive procedures — 90% laparoscopic and 10% robotic) [352]. After adjustment, the use of a minimally invasive procedure resulted in a significantly higher risk of death (HR 2.20; 95% CI, 1.15 to 4.19) or recurrence (HR 1.97; 95% CI, 1.10 to 3.50) in comparison with an open abdominal approach for tumor stage FIGO IB — but not in tumor stage FIGO IA (n = 244; death HR 0.73; 95% CI, 0.13 to 4.01; recurrence HR 0.34; 95% CI, 0.10 to 1.10).

This difference in the outcome relative to tumor size is also confirmed by another cohort study, although it is only available as an abstract [353]. The study included a total of 721 patients with FIGO IB1 cervical carcinoma, and the different access routes (open vs. minimally invasive) or techniques (with or without uterine manipulator) were compared retrospectively. It was shown that it was only for tumors > 2 cm that the open approach was significantly superior to the minimally invasive approach in relation to disease-free survival. In addition, this advantage was not demonstrable in comparison with the subgroup who underwent surgery without a uterine manipulator.

With regard to this specific question — whether radical hysterectomy should be performed as an open abdominal or minimally invasive laparoscopic or robot-assisted procedure — three meta-analyses have also been published [354], [355], [356]. 

In the publication by Jin et al. (2018), 229 patients undergoing robotic radical hysterectomy were compared with 913 patients receiving laparoscopic or 948 receiving open hysterectomies. Only reduced blood loss, fewer postoperative complications, and shorter hospital stays were reported when a minimally invasive procedure was used. Data on overall survival or disease-free survival were not provided in the paper [354].

The Park et al. research group already published similar results in 2016, although they included significantly more patients with robotic radical hysterectomy in the analysis (n = 821) [355].

Finally, a pure comparison between laparoscopy and open surgery was reported in a meta-analysis by Wang et al. published in 2015. This study also confirms the benefit of the minimally invasive approach in terms of less blood loss, fewer postoperative complications, and shorter hospital stays, but with significantly longer operating times [356].

In a cohort study in Germany, a total of 389 patients were included in accordance with the LACC study criteria. In contrast to the laparoscopic/robotic technique used in the LACC study, the patients underwent surgery with a combined transvaginal–laparoscopic approach without a uterine manipulator [357]. After a median follow-up period of 99 months (range 1–288 months), the 3-year, 4.5-year, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1%, respectively, and the overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. This very good oncologic outcome, based on retrospective data, supports the hypothesis that surgical tumor hygiene is necessary, and it should be validated in further randomized trials.

The value of purely robotic surgery in relation to the oncological outcome is unclear. There is a lack of large randomized studies to assess the value of this minimally invasive procedure. However, the general use of minimally invasive techniques does not appear to be recommendable, against the background of the phase III study published by Ramirez et al. The guideline group therefore recommends that patients with < FIGO IIB cervical carcinoma should be informed about the data and that an open abdominal radical procedure should be recommended up to FIGO stage IIA.

Lymphadenectomy is a diagnostic procedure. The optimal approach for lymphadenectomy cannot be deduced from the currently available data. However, staged female patients were found to have a better prognosis.

The preoperative laboratory tests that are necessary are:

• Blood count
• Electrolyte status
• Coagulation status
• Creatinine
• Creatinine clearance in the presence of hydronephrosis when planned chemotherapy is planned
• Transaminases, alkaline phosphatase, gamma-glutamyltransferase (GGT)
• Urinary status