Successful pregnancy with stage IB2 uterine cervical cancer: A case report

Abstract Background Although cervical cancer is one of the most common malignancies in pregnancy, its management mainly follows the guidelines for nonpregnant disease state. Within the limited time, patients, and healthcare workers must make difficult decisions to either delay treatment until documented fetal maturity or start immediate treatment based on the disease stage. Case The patient was a 37‐year‐old woman: gravida 1, para 0. Her cervical cytology revealed a high‐grade squamous intraepithelial lesion at 8 weeks' gestation. Moreover, invasive squamous cell carcinoma was suspected based on the findings of uterine cervix biopsy. Cervical conization was performed at 11 weeks' gestation, confirming a histopathological diagnosis of squamous cell carcinoma, pT1b2. Cervical cytology findings continued to be negative for intraepithelial lesion or malignancy from 2 weeks after conization until 2 weeks before a cesarean section. In addition, we performed abdominal pelvic lymphadenectomy at 16 weeks' gestation to determine whether the patient could continue her pregnancy. No lymph node metastasis or local recurrence was observed. Finally, a cesarean section and modified radical hysterectomy were performed at 35 weeks' gestation. There was no carcinoma invasion or metastasis. A baby girl weighing 2056 g was delivered with 1‐ and 5‐min Apgar scores of 8 and 9, respectively. Five years postoperatively, there was no evidence of cancer recurrence. Conclusion Management of cervical cancer during pregnancy by using a combination strategy of deep conization and pelvic lymphadenectomy could be an effective strategy for carefully and safely assessing risks of recurrence and metastasis.


| INTRODUCTION
Cervical cancer (CC) is one of the most common malignancies in pregnancy, with an estimated incidence of 1.2 to 1.5 cases per 10 000 births. 1,2 The incidence of abnormal cervical cytologic findings during pregnancy is $5%-8%. 3,4 Approximately 1%-3% of women with CC are diagnosed during or after pregnancy. 3,5 Stage I disease is three times more common in pregnant patients than in non-pregnant ones, which may be explained by routine prenatal cervical screening. 4,6 CC during pregnancy is expected to increase due to the marrying-late trend in Japan. Rarity of the disease and lack of randomized control studies have prevented the establishment of treatment guidelines. Disease management in pregnant women mainly follows the guidelines for nonpregnant disease state, expert opinions, and limited case reports. Invasive CC treatment during pregnancy should be individualized and managed according to cancer stages, patients' willingness to continue their pregnancy, and fetal maturity. Patients must make difficult decisions to either delay treatment until documented fetal maturity or undergo immediate treatment according to their disease stage.
Advances in neonatal medicine in recent years have improved the prognosis of premature births and provided varied management methods for these patients. However, there is no established recommendation for the care of pregnant women with CC. The present case report describes a woman diagnosed with CC, 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB2, during pregnancy in which a cesarean section followed by modified radical hysterectomy was performed at 35 weeks' gestation in our hospital.

| CASE
A 37-year-old primigravida Japanese woman presented to our hospital in her first trimester with a high-grade squamous intraepithelial lesion found in a Papanicolaou smear examination during the initial evaluation of her pregnancy. She did not have any relevant family history and had not undergone a cervical smear for at least 15 years. Colposcopy showed a white condyloma-like lesion in the posterior half of the uterine cervix ( Figure 1A). Cervical biopsy at 8 weeks' gestation revealed invasive keratinizing-type squamous cell carcinoma ( Figure 1B). We performed cervical conization at 11 weeks' gestation.
At the beginning of this surgery, in order to decrease blood loss, the whole circumference of the uterine cervix was sutured at 2 cm under the vaginal fornix using a 1-0 Maxon suture (Figure 2A). Subsequently, deep conization was performed with only 5 ml of blood loss. An elective cesarean section and modified radical hysterectomy were performed at 35 weeks' gestation. We made an incision in the upper part of the lower uterine segment, not to bother the uterine cervix for the following hysterectomy. A baby girl weighing 2056 g was delivered with 1-and 5-min Apgar scores of 8 and 9, respectively, and the baby was discharged from the neonatal unit 2 weeks later without any medical problems. Following delivery, a modified radical hysterectomy was performed using the extraperitoneal approach.
Since negative cervical cytology suggested no or slight remnant tumor found in the uterine cervix, we chose modified radical hysterectomy.
Without any complication, the duration of surgery was 155 min, the specimen weighed 977 g, and blood loss was 970 ml, including amniotic fluid. No evidence of residual disease was detected on histopathological examination. Thus, no adjuvant therapy was administered. We successfully treated the patient without any adverse events until she could deliver a healthy baby. The patient is still being monitored and has remained disease-free for 5 years. In addition to the first child described herein, the parents welcomed an adopted baby into their family 5 years after treatment.

| DISCUSSION
Current management of CC in pregnancy is based on recommendations for nonpregnant women. Published reviews indicated that pregnancy itself does not adversely affect the prognosis of CC. 4,7 Regarding postponement of treatment, the Practice Bulletin by the American College of Obstetricians and Gynecologists stated that delivery can be postponed by 6 weeks. 8 Unfortunately, in order for the fetus to survive, this recommendation is unsuitable in the Japanese context because cervical screening is performed during the first trimester in Japan.

| Radical trachelectomy
The number of cases of radical trachelectomy during pregnancy has increased. However, complications of this method are serious, such as infertility, constriction of the cervix after surgery, and increasing preterm delivery. Twenty-two case reports of radical trachelectomy during pregnancy have been published, including 16 live babies (72.7%). [9][10][11][12][13][14][15][16][17][18][19] Although radical trachelectomy is the most curative treatment during pregnancy, its technical difficulty causes limited access to available institutions. Enomoto et al., reported that from 2011 to 2014, they had four live babies after radical trachelectomy at 15 to 17 weeks' gestation. 16 Despite their results, previous reports from outside Japan showed that there was little chance to deliver mature babies. Regarding other complications aforementioned, high risks are associated with this surgery.

| Neoadjuvant chemotherapy
Some reviews of platinum-based neoadjuvant chemotherapy have been published recently. During the first trimester, the estimated teratogenic risk for the fetus ranges from 7.5% to 17% with single-agent therapy, which increases to 25% with combination cytotoxic chemotherapy. 20 If treatment is provided during the second and third trimesters, the rate of adverse effects is similar to that in normal pregnancies (1%-3%).
None of the reported cases showed any fetal abnormality following the use of neoadjuvant chemotherapy during pregnancy. However, the populations were small and self-selected. Additional outcomes of chemotherapy might include possible intrauterine growth restriction, fetal death, low birth weight, and premature birth. Furthermore, hematopoietic suppression, infertility, retarded development, carcinogenesis, and second-generation teratogenesis have been observed. 21

| Pelvic lymphadenectomy
For women who wish to continue their pregnancy but are at significant risk for lymph node metastases, staging lymphadenectomy via laparotomic, or laparoscopic approaches may provide important information on the lymph node status. Lymph node involvement is an important prognostic factor for CC. 23 Several studies have reported the feasibility of lymphadenectomy during pregnancy. [24][25][26][27] In a study of 31 patients, lymphadenectomy was rarely associated with maternal or fetal morbidity. 14, 28 We chose the laparotomic approach to perform the surgery within a short duration to minimize any possible anesthetic influence on the fetus, paying attention not to press the uterus. Presence of positive nodes modifies therapeutic approaches and alters pregnancy outcomes. Lymph node-positive pregnant women should terminate their pregnancy or be informed of the need for immediate treatment, including neoadjuvant chemotherapy. Notably, when the tumor diameter is ≤2 cm, the frequency of pathological parametrial invasion and lymph node metastasis is reportedly very low, and relapse-free survival remains good. 29 reported that 85 patients with tumors measuring <2 cm or a depth of invasion of ≤10 mm had a 5-year DFS of 95.3%. 30 Staging procedures and identification of regional lymph node spread must be performed appropriately.
In the present report, we first performed cervical conization to assess whether the tumor size was ≤2 cm specifically. To summarize, this case report describes the management of CC diagnosed during pregnancy with cervical conization and abdominal pelvic lymphadenectomy in the first and second trimesters, respectively. Since the risk of premature birth caused by radical trachelectomy remains high, a combination strategy of cervical conization and pelvic lymphadenectomy could represent an important option for evaluating metastatic risks among pregnant women with CC. Treatment plans are continuously evolving with individualized therapy for optimal outcomes of both the mother and her unborn fetus. Stage at diagnosis, tumor size, nodal status, histological subtype, and gestational age all have influenced the available therapeutic options and outcomes. Each specific case should be discussed and agreed individually when pregnant women are diagnosed with CC. This case indicated that pregnancy could be preserved if the patient had no evidence of lymph node metastasis. The important ethical, emotional, and social development dilemmas of the treatment options for the patient and medical team should also be considered. Therefore, decisions have to be made by the patient and a multidisciplinary team of obstetricians, gynecologists, oncologists, and neonatologists.

ACKNOWLEDGMENTS
We would like to thank Dr. Matsumoto and Dr. Sakaguchi for their technical assistance. We also appreciate Editage (www.editage.com) for English language editing.