Four Surgical Approaches to Cervical Excision During Laparoscopic Radical Trachelectomy for Early Cervical Cancer

Accepted Manuscript Four Surgical Approaches to Cervical Excision During Laparoscopic Radical Trachelectomy for Early Cervical Cancer José Saadi, MD, Lucas Minig, MD, PhD, Florencia Noll, MD, Gabriel Saraniti, MD, José Miguel Cárdenas-Rebollo, PhD, Myriam Perrotta, MD, PhD PII:

S1553-4650(17)30266-2

DOI:

10.1016/j.jmig.2017.04.010

Reference:

JMIG 3120

To appear in:

The Journal of Minimally Invasive Gynecology

Received Date: 7 March 2017 Revised Date:

8 April 2017

Accepted Date: 11 April 2017

Please cite this article as: Saadi J, Minig L, Noll F, Saraniti G, Cárdenas-Rebollo JM, Perrotta M, Four Surgical Approaches to Cervical Excision During Laparoscopic Radical Trachelectomy for Early Cervical Cancer, The Journal of Minimally Invasive Gynecology (2017), doi: 10.1016/j.jmig.2017.04.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Four Surgical Approaches to Cervical Excision During Laparoscopic Radical Trachelectomy

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for Early Cervical Cancer

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José Saadi, MD*, Lucas Minig, MD, PhD, Florencia Noll, MD, Gabriel Saraniti, MD, José Miguel

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Cárdenas-Rebollo, PhD, Myriam Perrotta, MD, PhD

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From the Department of Gynecology, Gynecologic Oncology Unit, Hospital Italiano de Buenos Aires,

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Buenos Aires, Argentina (Drs Saadi, Noll, Saraniti, Perotta), Gynecology Department, Valencian

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Institute of Oncology, Valencia, Spain (Dr Minig), and Department of Applied Mathematics and

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Statistics CEU San Pablo University, Madrid, Spain (Dr. Cárdenas-Rebollo).

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Corresponding author: José Saadi, MD Gynecology Department Gynecologic Oncology Unit Hospital Italiano de Buenos Aires Buenos Aires, Argentina Castex 3472 2B (C1425), Telephone: 54 9 11 68262354 E-mail: [email protected]

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The authors declare that they have no conflict of interest.

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Abstract

25 A retrospective analysis was performed at the Gynecology Department of the Hospital Italiano de

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Buenos Aires in Buenos Aires, Argentina to compare clinical and oncologic outcomes of four different

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surgical approaches of cervical excision (CE) during radical trachelectomy (RT) for early cervical

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cancer. The study included 22 consecutive women who had undergone laparoscopic RT for early

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cervical cancer between May 2011 and July 2016 in our tertiary care hospital. Patients were divided

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into four groups according to their respective tumor pathologies and surgical approaches. A total of 5

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(22.7%) patients had International Federation of Gynecology and Obstetrics (FIGO) stage IA2, and 17

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(77.3%) had FIGO stage IB1. Squamous carcinoma was diagnosed in 17 (77.3) patients. Mean surgical

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time for all patients was 277.5 (± 47 standard deviation [SD]) minutes with 289.3 (± 36 SD), 265.0 (±

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32 SD), 266.7 (± 67 SD), and 2967 (± 60 SD) minutes for type A, B, C, and D CEs, respectively. Mean

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estimated blood loss was 345.5 (± 88 SD) mL. Mean hospital length of stay was 2.5(± 0.7 SD) days. No

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intraoperative complications were observed. One patient presented with cervical stenosis and

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another Asherman’s syndrome, both after type B CE. Only grade 1/2 postoperative complications

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were noted in 9 patients. One local recurrence after type B CE was treated with radical hysterectomy

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plus chemoradiation; while another patient relapsed with peritoneal carcinomatosis managed with

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chemotherapy after type A CE. The different types of cervical excisions should be determined on a

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case by case basis according to individual tumor factors.

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Keywords: fertility-sparing surgery; laparoscopy

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Precis: The type of cervical excision during trachelectomy should be determined according to

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individual tumor factors.

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Radical trachelectomy (RT) is considered a therapeutic alternative for patients impacted by early stage cervical cancer who wish to preserve their fertility [1]. The procedure, however, can only

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be offered to patients with ≤ 2 cm tumor limited to the cervix, no evidence of pelvic lymph node

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disease or other distant metastasis, favorable histologic types, and clear inner margins must be

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present between the cervix and uterine corpus [2].

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Radical trachelectomy has been extensively described using different surgical approaches such as vaginal, abdominal, or through minimally invasive surgery [3-7]. Lee et al first described the

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technique by laparoscopy [8]. From an oncologic perspective, the cervical excision (CE) from the

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uterine corpus is a key surgical step requiring technical precision to achieve disease-free internal

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cervical margins. However, using an electrosurgical unit or cold knife can pathologically alter the area

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between the cervix and uterine corpus [9]. In addition, cervical competence during pregnancy can be

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reduced depending on the extent of the CE [10-11]. Some authors, on the other hand, recommend

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not manipulating the cervix into the abdominal cavity during CE to avoid possible tumor

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contamination of the peritoneum [12] making CE an important step during RT. The aim of this study is

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to describe the clinical and oncologic outcomes of four different surgical approaches used to perform

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CE during RT in women affected by early cervical cancer.

64 Materials and Methods

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After Institutional Review Board approval, a retrospective analysis was performed at the

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Gynecology Department of the Hospital Italiano de Buenos Aires in Buenos Aires, Argentina. The

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study comprised 22 consecutive women who had undergone laparoscopic RT for cervical cancer

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between May 2011 and July 2016. They were divided into four groups according to the different

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surgical approaches performed.

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Clinical information was abstracted from medical records and included baseline patient

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characteristics, clinical International Federation of Gynecology and Obstetrics (FIGO) stage, surgical

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time, estimated blood loss (EBL), hospital length of stay (LOS), final histology diagnosis, intraoperative

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and postoperative complications, as well as oncologic outcomes. Operating time was defined as

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fromskin incision to skin closure. The EBL was calculated by the difference between the total amount

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extracted and irrigated fluids. Complications were classified from grade I to IV [13] and were recorded

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throughout hospital stay, in case of readmission, or at first postoperative check within 4 to 8 weeks

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following surgery. Inclusion criteria were desire to preserve fertility, tumor ≤ 2 cm, squamous and

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adenocarcinoma histology types, FIGO stage 1A2-1B1, no evidence of distant metastasis, and no

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medical conditions that would contraindicate laparoscopic minimally invasive surgery. The

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classification and staging of cervical cancer was performed according to the FIGO staging system [14].

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Patients with tumor sized 2 to 3 cm underwent RT after neoadjuvant chemotherapy of 3 courses of

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carboplatin and paclitaxel. All patients were preoperatively evaluated by pelvic examination, pelvic

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magnetic resonance imaging (MRI), as well as computed tomography (CT) of the chest-abdomen and

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pelvis.

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Surgical Techniques

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All patients underwent RT with pelvic lymphadenectomy as described elsewhere [5]. Four laparoscopic trocars were placed: a 12-mm trocar was placed in the umbilicus for the camera,10-mm

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trocar in the right iliac fossa, 5-mm trocar in the left iliac fossa, and 5-mm trocar in the suprapubic

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region. The patient was placed in the Trendelenburg lithotomy position, with compression stockings

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worn during surgery to prevent thromboembolic events. The uterus was mobilized by placement of a

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VCare manipulator (ConMed, Utica, New York). Pneumoperitoneum was established and maintained

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with 12 mm Hg pressure and the Harmonic scalpel (UltraCision; Ethicon Endo-Surgery, Cincinnati,

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Ohio) was used during all surgical procedures. The peritoneum was sectioned anteriorly and

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posteriorly to the round ligaments (both preserved), parallel to the ovarian vessels. The

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retroperitoneum was exposed to the junction of the ureter and iliac artery. A bilateral pelvic

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lymphadenectomy was performed from the circumflex vein to the junction of the ureter and external

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iliac artery. The external iliac, hypogastric, and obturator lymph nodes were completely removed. The

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pelvic lymph nodes were sent for frozen section. Both paravesical spaces were dissected to the pelvic muscles, with exposure of the vascular

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structures (vesical artery and uterine artery), ureter, and vaginal lateral wall. Both uterine arteries

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were ligated in the first four procedures, while they were preserved in all the remaining cases. The

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ureter was dissected with the Harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, Ohio) from the

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lateral parametrium until its insertion into the bladder. The pararectal and rectovaginal spaces were

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dissected prior to the lateral and posterior parametrium, also with the Harmonic scalpel (Ethicon

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Endo-Surgery, Cincinnati, Ohio).

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The type of CE was determined based on tumor factors described below with the purpose of obtaining a tumor-free margin, confirmed by frozen section, with a neocervix of 1 to 1.5 cm below

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the internal cervical os. If the pathologist confirmed a disease-free margin in the specimen, an

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additional 5-mm margin in the remaining cervix was also removed for pathologic review. Radical

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hysterectomy was performed if the latter margin was affected by disease. Performing the colpectomy

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and specimen removal completed the procedure. An intrauterine 8-mm silicone catheter was

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inserted and sutured into the neocervix and attached with a 2-0 Vicryl suture (Ethicon, Somerville,

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New Jersey). It was then removed 15 days after surgery. The uterovaginal anastomosis was

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performed with four stiches of 2-0 Vicryl suture (Ethicon, Somerville, New Jersey). A cerclage with 0

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polypropylene (PROLENE®; Ethicon, Somerville, New Jersey) was performed by laparoscopy in Type A

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and B CE, and vaginally in Type C and D CE. The fallopian tubes and ovaries were preserved, and the

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urinary catheter was left in place for 7 to 10 days after surgery.

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Type A: Internal Cervical Excision Before Parametrial Resection and Colpectomy. This surgical

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technique was used in the first 7 patients and previously published [5]. The cervix is sectioned 2 cm

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above the cervical margin by using the Harmonic scalpel (Ultracision; Ethicon Endo-Surgery,

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Cincinnati, Ohio), which is delineated by the VCare® uterine manipulator (ConMed, Utica, New York).

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Once the cervix is separated from the uterine corpus, a frozen section of the internal margin must

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confirm absence of disease. Then, lateral and posterior parametrium are sectioned and colpectomy is

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performed. This initial experience mimicked the surgical laparotomy technique previously noted by

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the same group [15].

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By using this approach, the tumor is not manipulated into the peritoneal cavity thus, avoiding

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tumor contamination. However, the difficulty to palpate the tumor could lead to excessive resection

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of the cervix and potential negative obstetrical consequences owing to cervical incompetence.

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Type B: Internal Cervical Excision After Parametrial Resection and Colpectomy. Burnett et al

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previously described this technique in 2009 [16]. As the uterine arteries are preserved, the resection

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of lateral parametrium is the most difficult step of the procedure. Then, the surgical technique is

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similar as described above. Once the lateral and posterior parametrium are sectioned, colpectomy is

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performed just below the uterine arteries. This alternative strategy, technically more difficult, has the

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potential limitation of tumor peritoneal contamination owing to the surgical specimen being free in

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the abdominal cavity.

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Type C: External Cervical Excision After Parametrial Resection and Colpectomy. The entire uterus is

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removed through the vagina, after posterior and lateral parametrium have been transected and

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colpectomy completed laparoscopically. Special care of the uterine arteries, which have been

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previously preserved, is crucial to avoid vessel damage. Normally, the resection margin of the cervix is

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adequately visualized in the vagina while tumor contamination into the abdominal cavity is avoided.

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A cold knife is commonly used to separate the cervix from the uterus. (Fig. 1)

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Type D: External Cervical Excision After Vaginal Margin Closure. This surgical technique is a

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modification of type C CE and includes the closure of the vagina before the colpectomy and the CE.

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First, the vaginal mucosa is closed from the anterior to the posterior wall with a running suture. Then,

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the colpectomy is performed and the anterior and posterior vaginal walls are closed with another

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running suture before external CE, avoiding any risk of peritoneal contamination (Fig. 2). Type D

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surgery isolates the tumor from the peritoneal cavity and is, therefore, used in case of exophytic

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tumors.

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For all types of CE, the anastomosis between the vagina and the uterine corpus can be

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completed either vaginally or laparoscopically, according to surgeon preference. The vaginal

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approach, however, allows a better orientation of the internal os, obtaining a direct visualization of

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the suture and potential reduction of cervical occlusion by the vaginal mucosa.

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The type of CE was determined according to tumor size, colposcopic image, length of the

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cervix, as well as the endocervical measurement by MRI scan. As noted earlier, type A CE was used in

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the first 7 cases. Type B was applied in difficult cases to removed the uterus through the vagina if a

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tumor presented at pelvic MRI; type D CE was reserved for those cases with exophytic tumors; while

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all other cases were managed with type C CE.

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Statistical Analysis

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Kolmogorov-Smirnov with Lilliefors correction was used to evaluate the normal distribution of

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data. Whereas frequencies and proportions were used as summary statistics for categorical variables,

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mean and standard deviation (SD) were used for the continuous variables. Statistical analysis was

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performed using the IBM Statistical Package for the Social Sciences (SPSS) version 20.0 program.

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Results

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During the study period, 22 patients met inclusion criteria and underwent laparoscopic RT for early cervical cancer. A total of 7, 6, 6, and 3 patients underwent Type A, B, C, and D CE, respectively.

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Table 1 details the baseline characteristics. Mean age and BMI was 32.1 (± 5.2) years and 22.5 (± 2.6),

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respectively. A total of 3 (13.6%) patients presented comorbidities, which included cardiopathy,

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hypothyroidism, and von Willebrand disease.

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A total of 5 (22.7%) patients had FIGO stage IA2, and 17 (77.3%) had FIGO stage IB1. Among the FIGO stage IB1group, 16 patients had a tumor < 2 cm, while one patient had a tumor of 3 cm.

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After multidisciplinary counseling, the patient underwent neoadjuvant chemotherapy (3 courses of

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carboplatin and paclitaxel), and RT was performed after achieving partial response from the

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chemotherapy. Squamous carcinoma was diagnosed in 17 (77.3%) of patients. Mean tumor size and

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pelvic nodes removed were 11.2 (± 5.3) mm and 15.6 (± 3.8), respectively. All pathologically examined

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specimens were absent of parametrial involvement, margins were negative for disease as were pelvic

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lymph nodes. No patients required adjuvant treatment following RT (Table 1).

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Mean surgical time for all patients was 277.5 (± 47) minutes; with 289 .3 (± 36), 265.0 (± 32),

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266.7 (± 67), and 296.7 (± 60) minutes in type A, B, C, and D CE, respectively. Mean EBL was 345.5 (±

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88) mL. Intraoperative complications were not observed, and blood transfusion was not required in

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any patient. Mean hospital length of stay was 2.5 (± 0.7) days (Table 2). A full description of each postoperative complication and treatment is detailed in Table 3. One patient presented cervical stenosis and one more had Asherman’s syndrome, both after type B

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CE. Asherman’s syndrome was resolved with oral contraceptives for six months. One year following

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treatment cessation, the patient returned with regular menses.

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Median follow-up for the entire cohort was 16.2 (range, 1.1-60.4) months. Pregnancy was achieved by two patients overall, both after type B CE. One patient achieved a full-term delivery and

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the other a preterm delivery at 29 weeks of gestation (Table 4). Two (9%) patients relapsed (Table 5).

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The first patient underwent RT with type B CE for cervical cancer FIGO stage IB1. The final pathology

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report noted a 10-mm squamous cervical carcinoma moderately differentiated (G2) with disease-free

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resection margins and absence of lymphovascular space invasion. She had a vaginal cuff relapse 9

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months later, which was treated with radical hysterectomy followed by concurrent chemoradiation.

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The second patient underwent RT with type A CE for cervical cancer FIGO stage IB1. The final

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pathology report noted a 15-mm squamous cervical carcinoma moderately differentiated (G2) with

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disease-free resection margins and absence of lymphovascular space invasion. She presented with

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peritoneal carcinomatosis 16 months following RT, which was treated with carboplatin with paclitaxel

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and bevacizumab. Both patients were alive without evidence of disease at last follow-up.

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Discussion

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To our knowledge, this is the first study to describe four different surgical approaches to perform CE during laparoscopic RT in women with early cervical cancer. Even though similar clinical

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and oncologic outcomes were found among patients undergoing the different types of CEs in the

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initial pilot study, some comments need to be made.

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Determining the type of CE as compared with the others should be individualized for each

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patient, taking into consideration specific tumor factors including tumor size, distance between the

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tumor and the internal os, ability to remove the uterus through the vagina, the presence or absence

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of exophytic tumors, as well as the expertise and preference of each surgeon. Thus, in patients where

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removing the uterus through the vagina is difficult or in women with very small tumors, CE can be

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performed intra-abdominally in types A or B, as previously described. In these cases, pelvic MRI is

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useful to establish the distance between the tumor and the internal os [17].

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Types C and D CE are used if the uterus can be externalized through the vagina. This allows palpating the cervix and the tumor, the measurement of the cervical length, and to performing a

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more accurate CE in accordance with tumor extension into the cervix. Therefore, we typically apply

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type C CE, given that it is more accurate in determining the appropriate resection line and less

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demanding than the intra-abdominal types (Type A and B). On the other hand, Type D CE should be

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reserved for those cases with exophytic tumors.

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Establishing the appropriate margin of CE is very important to achieve a disease-free margin,

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which must be at least 5 mm away from the tumor [18]. Thus, the surgical type of CE is based on the

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tumor size and length [19], avoiding over resection that may shorten the cervix excessively. This fact

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may be associated with a potential negative impact on future pregnancies owing to cervical

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incompetence [20]. In this regard, when the CE occurs 10 mm or less toward the internal os, the

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possibility of cervical stenosis or incompetence is greater [21,22]. Even though controversial, a

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cerclage has been proposed to prevent cervical incompetence and preterm delivery following RT [23].

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Uterine artery preservation at the time of RT is important, and those in favor of preserving uterine vessels argue that better uterine vascularization avoids negative impact on future fertility,

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without compromising oncologic outcomes. However, it is still premature to establish a formal

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recommendation on whether or not preserving uterine arteries does help preserve fertility based on

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the small sample size of the studies reported to date [24].

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Tumor relapse and mortality after RT is estimated at 4% and 3%, respectively [11]. Schneider

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et al suggested possible peritoneal contamination during tumor removal as a potential causes of

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tumor recurrence after laparoscopic RT thereby, highlighting the importance of tumor isolation

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before removal [12]. Therefore, determining the type of CE seems relevant to prevent tumor

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relapses. In addition, even though the use of uterine manipulators has been a subject of debate as a

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possible contaminator of the peritoneal cavity, there is still no evidence to demonstrate correlation

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[25]. As previously described, a VCare® uterine manipulator (ConMed, Utica, New York) has been

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used in all the procedures reported in the present study. Taking into account the entire cohort of

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patients, this study reports clinical and oncologic outcomes that are in accordance with other series

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[20].

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Being the first study of its nature and a homogeneous group of patients with specific inclusion criteria are the strengths of this study. The primary limitation is that the data were

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retrospectively collected and the second limitation is that the sample size is small with short follow-

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up. Finally, the learning curve during the study period and possible selection bias could have

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impacted the results.

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Conclusion

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Cervical excision is a very important surgical step during laparoscopic radical trachelectomy. The four types of cervical excisions described herein should be used according to each case based on

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specific tumor factors. Even though no clinical or oncologic differences were found among the four

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types of CE, future studies with a bigger sample size are required to confirm present results.

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FIGURE LEGENDS:

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Fig. 1

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Type C cervical excision. (A) The uterus was pulled into the vagina with a hysterometer placed in the

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cervix to determine the length of the channel. (B) A cold knife was used to perform the cervical

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excision.

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Fig. 2

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Type D cervical excision. (A) Tumor isolation by vaginal occlusion. (B) Cervical incision after tumor

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isolation near the vaginal mucosa.

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Table 1 Baseline characteristics

Parity, n (%)

IA2 IB1 Squamous Adenocarcinoma 1 2 3

5 (22.7) 17 (77.3) 17 (77.3) 5 (22.7) 7 (31.8) 11 (50) 4 (18.2) 5 (22.7) 11.2 (± 5.3) 10.5 (3-20) 15.6 (± 3.8) 16.0 (10-25)

Histology type, n (%) Grade, n (%)

LVSI, n (%) Tumor size, mm

Pelvic node count

Mean ± SD Median (min-max) Mean ± SD Median (min-max)

AC C

FIGO Stage, n (%)

Type D (n = 3)

33.2 (± 5.0) 32.5 (27-40) 23.0 (± 3.2) 23.0 (19-27) 6 (100) 0 6 (100) 0 1 (16.7)a

32.2 (± 5.4) 33.5 (22-37) 22.8 (± 2.9) 23.5 (19-26) 3 (50) 3 (50) 1 (16.7) 5 (83.3) 2 (33.3)b

31.7 (± 2.9) 30.0 (30-35) 23.3 (± 1.5) 23.0 (22-25) 1 (33.3) 2 (66.7) 1 (33.3) 2 (66.7) 0

4 (66.7) 2 (33.3) 4 (66.7) 2 (33.3) 1 (16.7) 4 (66.7) 1 (16.7) 2 (33.3) 11.0 (± 6.1) 10.0 (3-20) 14.3 (± 3.6) 14.5 (10-19)

1 (16.7) 5 (83.3) 5 (83.3) 1 (16.7) 4 (66.7) 2 (33.3) 0 3 (50) 8.3 (± 3.1) 8.5 (5-12) 15.5 (± 2.5) 14.5 (12-21)

0 3 (100) 3 (100) 0 0 2 (66.7) 1 (33.3) 0 16.0 (± 4.6) 17.0 (11-20) 15.3 (± 2.3) 14.0 (14-18)

RI PT

30.9 (± 6.6) 30.0 (22-39) 21.3 (± 2.1) 22.0 (18-23) 5 (71.4) 2 (28.6) 4 (57.1) 3 (42.9) 0

Type C (n = 6)

SC

32.1 (± 5.2) 32.5 (22-40) 22.5 (± 2.6) 22.5 (18-27) 15 (68.1) 7 (31.9) 12 (54.5) 10 (45.5) 3 (13.6)

Comorbidities, n (%)

Type B (n = 6)

M AN U

Previous surgeries, n (%)

Mean ± SD Median (min-max) Mean ± SD Median (min-max) 0 1 0 1

0 7 (100) 5 (71.4) 2 (28.6) 2 (28.5) 3 (42.8) 2 (28.5) 0 11.7 (± 5.5) 15.0 (3-18) 16.9 (± 4.8) 17.0 (10-25)

TE D

BMI, kg/m2

Type A (n = 7)

EP

Age, years

All (N = 22)

Abbreviations: BMI = body mass index; FIGO = International Federation of Gynecologists and Obstetricians; LVSI = lymphovascular space involvement; min-max = minimum to maximum; SD = standard deviation.

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EP

TE D

M AN U

SC

RI PT

(n = 1) and von Willebrand disease (n = 1).

AC C

aCardiopathy; bHypothyroidism

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Table 2 Intraoperative and postoperative characteristics

Hospital length of stay, days

345.5 (± 88) 300 (250-500) 277.5 (± 47) 275.0 (190-360)

Mean ± SD

2.5 (± 0.7)

Median (min-max)

2.0 (2-4)

371.4 (± 75) 400 (300-500) 289.3 (± 36) 280.0 (250-360)

RI PT

Surgical time, min

Mean ± SD Median (min-max) Mean ± SD Median (min-max)

Type B (n = 6)

3.3 (± 0.8) 3.0 (2-4)

Type C (n = 6) 291.7 (± 58) 275 (250-400) 266.7 (± 67) 270.0 (190-360)

500.0 (± 0) 500 (0) 296.7 (± 60) 290.0 (240-360)

2.5 (± 0.5)

2.0 (± 0)

2.3 (± 0.6)

2.5 (2-3)

2.0 (0)

2.0 (2-3)

EP

TE D

Abbreviations: EBL = estimated blood loss; min = minutes; min-max = minimum to maximum; SD = standard deviation.

AC C

Type D (n = 3)

291.7 (± 20) 300 (250-300) 265.0 (± 32) 250.0 (240-310)

SC

EBL, mL

Type A (n = 7)

M AN U

All (N = 22)

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Table 3 Postoperative complications

Postoperative complications

Type B (n = 6)

Type C (n = 6)

Frequency, n (%)

Type D (n = 3) Treatment

RI PT

Type A (n = 7)

Radiologic

Surgery

2 2 1 1 2 1 1 0

0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0

AC C

EP

TE D

M AN U

SC

Minor (grade 1-2) Subcutaneous emphysema 1 (14.3) 1 (16.7) 0 0 Pelvic lymphocele 1 (14.3) 0 1 (16.7) 0 Pelvic hematoma 1 (14.3) 0 0 0 Abdominal abscess 0 1 (16.7) 0 0 Urinary tract infection 0 0 1 (16.7) 1 (33.3) Cervical stenosis 0 1 (16.7) 0 0 Asherman’s syndrome 0 1 (16.7) 0 0 Major (grade 3-5) 0 0 0 0 *Chi-square; two-sided Fisher’s exact test or Wilcoxon test where appropriate.

Medical

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Table 4 Oncologic and obstetrics characteristics Type A (n = 7)

Type B (n = 6)

Median follow-up, months (range)

16.2 (1.1-60.4)

47.5 (19.1-60.4)

15.9 (12.2-33.9)

13.9 (1.1-15.4)

5.0 (3.7-6.3)

Patients with relapse, n (%)

2 (9.1)

1 (14.3)

1 (16.7)

0

0

Patients alive, n (%)

22 (100)

7 (100)

6 (100)

6 (100)

3 (100)

Pregnancies, n (%)

2 (9.1)

0

2 (33.3)

0

0

Miscarriage, n (%)

0

0

0

0

0

Preterm delivery, n (%)

1 (4.5)

0

1 (50)

0

0

SC

M AN U

TE D EP AC C

Type C (n = 6)

RI PT

All (N = 22)

Type D (n = 3)

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Table 5 Clinical characteristics of patients with relapsed disease Patient 1 Type of surgical cervical excision B

Patient 2 A

1B1

1B1

Histology

Squamous

Squamous

Maximum tumor size, mm

10

15

Differentiation, grade

2

2

Resection margins

Negative

Negative

Lymph node positive/removed

0/13

0/25

LVSI

Negative 9

Site of relapse

Vaginal cuff

Negative 16

Peritoneal carcinomatosis Chemotherapy: carboplatin + paclitaxel + bevacizumab

EP

TE D

Radical hysterectomy + concurrent chemoradiation Abbreviations: FIGO = International Federation of Gynecologists and Obstetricians; LVSI = lymphovascular space involvement.

AC C

Treatment

M AN U

Disease-free survival, months

SC

FIGO stage

RI PT

Histology characteristics

AC C

EP

TE D

M AN U

SC

RI PT

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AC C

EP

TE D

M AN U

SC

RI PT

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