The purpose of this study was to update the management of invasive cervical cancers diagnosed during pregnancy. Patients and methods: This study was performed retrospectively at radiotherapy department of National Institute of Oncology Rabat Morocco. From 01/04/2005 to 31/05/2010 , ten patients with invasive cervical cancer during pregnancy were included. Results: Ten patients were included in the study. The staging was as follow: stage IIIB (n = 4); stage IIB (n = 2) and stage IB2 (n = 4). The radical abdominal hysterectomy with pelvic lymphadenectomy was performed in five patients; a therapeutic interruption of pregnancy was performed in four patients. One pregnancy has resulted in the birth of a living child (by cesarean section). Adjuvant treatment was concomitant chemoradiotherapy followed by low dose rate (LDR) brachytherapy in three patients; adjuvant concomitant chemoradiotherapy followed by high dose rate (HDR) brachytherapy w as performed in four patients; a HDR brachytherapy was done in one patient. Two patients have received an exclusive external radiotherapy. After a median follow-up of 4 years (2 - 7 years), there were bone and lung metastas e s in one patient. Nine patients are alive after completed treatment. Conclusion: Our series focused on ten patients with invasive cervical cancer during pregnancy. Management is complex and requires discussion in a multidisciplinary meeting. Routine screening of cervical cancer and awareness are the key point to improve the treatment and survival rate of patients. The management of all cases is according to international recommendations.
Cervical cancer during pregnancy is a rare situation; this malignant tumor is one of the most commonly diagnosed cancers during pregnancy (with hematologic malignancy, breast cancer and melanoma). Its incidence, according to the populations, varies between one and ten per 10,000 pregnancies [
It was a retrospective study from 01/04/2005 au 31/05/2010. We included pregnant patients with confirmed cervical cancer. We obtained a clear consent from patients before inclusion.
Non-pregnant patients with cervical cancer were excluded. Patients were grouped according to the age of pregnancy, the histological type, tumor size, and the classification of the International Federation of Gynecology and Obstetrics. We have analyzed the clinical, pathological and therapeutic features of the patients. The treatment was (radical abdominal hysterectomy with pelvic lymphadenectomy or concomitant radiochemotherapy or exclusive radiotherapy or brachytherapy). The simulation was done at CT scan. Radiotherapy was administered with linear accelerator 18 MV; the concomitant chemotherapy was cisplatin 40 mg/m2/week. Brachytherapy with FLEXITRON V3 projector. Data was analyzed on SPSS version 20 (SPSS Inc., Chicago, IL).
Ten patients were included. The median age was 32 years old (range 21 - 35), all the patients were multiparous, and the average of the pregnancies was 18.6 weeks of gestation (WG). Clinical aspects were dominated by spontaneous bleeding with leucorrhea and pelvic pain. The patients had no pathological antecedents or notions of gynecological follow-up. The biopsy had objectified squamous cell carcinoma in eight cases, adenocarcinoma in two patients. The diagnosis of cancer was made in the first quarter in nine cases and in the third quarter in one case. The median time to diagnosis was 2 months (range 1 - 9) (
The extension work up consisted on an abdominal and pelvic ultrasound performed in all patients. Magnetic resonance imaging (MRI) was performed in one patient at 10 weeks of gestation. Abdominal and pelvic CT scan was performed after Radical abdominal hysterectomy with pelvic lymphadenectomy in five patients and after therapeutic interruption of pregnancy in four patients; this CT scan had objectified pelvic lymph node involvement in three patients. Chest X ray was performed in nine patients (five patients after hysterectomy; four patients after therapeutic interruption of pregnancy and in a patient after cesarean section). The patients were classified, according to the classification of International Federation of Gynecology and Obstetrics (FIGO) 2002 in stage IIIB (n = 4) 40%, IIB (n = 2) 20% and stage IB2 (n = 4) 40%.
Nine were sent by regional centers and had already undergone surgery after informed consent: Five patients had undergone radical abdominal hysterectomy with pelvic lymphadenectomy, adjuvant therapy in these patients was in case 3, HDR vaginal brachytherapy with tandem and cylinder applicator at the dose of 3 weekly sessions of 7 Gy prescribed at 0.5 cm from the surface of the applicator. In four patients (cases 1, 4, 8, 9), adjuvant therapy included external beam radiotherapy by photons × 25 MV at the dose of 46 Gy in 2 Gy per fraction in five sessions per week associated with concomitant cisplatin 40 mg/m2 per week; then the complement by HDR brachytherapy in 2 weekly sessions of 7 Gy prescribed at 0.5 cm from the surface of the applicator (See
In patient N˚ 2, the cancer is diagnosed during pregnancy at 39 WG, resulted in the birth of a child living by cesarean section. Lymph node dissection performed during cesarean section was positive, exclusive external beam radiotherapy at a dose of 70 Gy in 2 Gy per fraction and 35 fractions was adjuvant treatment (reason was the detection of kidney failure).
CASE | Age of patients (years) | Term of pregnancy (WG) | Circumstance diagnosis | Histology | Size at diagnosis (cm) | FIGO (initial) | Treatment | Histology | the delay Diagnosis- Treatment | Survival/month |
---|---|---|---|---|---|---|---|---|---|---|
1 (2005) | 31 | 11 | spontaneous and post coital metrorrhagia | Moderately differentiated squamous | >4 | IB2 | 1) TIP by laparotomy 2) concomitant radio-chemotherapy 46 Gy, 2 Gy/fr + cisplatin 40 mg/m2 and brachytherapy 24 Gy | N(p) + N(Ao) − | 5 weeks | 84 |
2 (2007) | 33 | 39 | spontaneous and post coital metrorrhagia | Moderately differentiated squamous | 5 | IIIB | 1) cesarean at 39 WA 2) external RTH 70 Gy, 2 Gy/fr | N(p) + N(Ao) − | 8 weeks | 60 |
3 (2007) | 31 | 10 | spontaneous and post coital metrorrhagia | Moderately differentiated ADK | >4 | IB2 | 1) TIP by laparotomy 2) brachytherapy HDR 3 × 7 Gy | N(p) − N(Ao) − | 3 weeks | 60 |
4 (2008) | 21 | 8 | spontaneous metrorrhagia + loss whitish | Moderately differentiated ADK | >4 | IB2 | 1) TIP by laparotomy 2) concomitant radio-chemotherapy 46 Gy, 2 Gy/fr + cisplatin 40 mg/m2 and brachytherapy HDR 2 × 7 Gy | N(p) ? and insufficient N(Ao) − | 2.5 weeks | 48 |
5 (2008) | 35 | 11 | spontaneous and post coital metrorrhagia | differentiated squamous little | 6 | IIIB | 1) TIP 2) concomitant radio-chemotherapy 46 Gy, 2 Gy/fr + cisplatin 40 mg/m2 and brachytherapy LDR 24 Gy | No lymphadenectomy | 3 weeks | 48 |
6 (2008) | 32 | 8,6 | spontaneous and post coital metrorrhagia | Moderately differentiated squamous | 7 | IIIB | 1) TIP 2) concomitant radio-chemotherapy 46 Gy, 2 Gy/fr + cisplatin 40 mg/m2 and brachytherapy LDR 24 Gy | No lymphadenectomy | 3 weeks | 48 |
7 (2009) | 34 | 10 | spontaneous and post coital metrorrhagia | Moderately differentiated squamous | 6 | IIIB | 1) TIP 2) external RTH 70 Gy, 2 Gy/fr | No lymphadenectomy | 2 weeks | 36 |
8 (2009) | 33 | 8 | metrorrhagia spontaneous and post coital | Moderately differentiated squamous | 5 | IIBproxi | 1) TIP by laparotomy 2) concomitant radio-chemotherapy 46 Gy, 2 Gy/fr + CDDP 40 mg/m2 and brachytherapy HDR 2 × 7 Gy | N(p) + N(Ao) − | 2 weeks | 36 |
9 (2010) | 30 | 10 | spontaneous and post coital metrorrhagia | Moderately differentiated squamous | 3 | IIBproxi | 1) TIP by laparotomy 2) concomitant radio-chemotherapy 46 Gy, 2 Gy/fr + cisplatin 40 mg/m2 and brachytherapy HDR 2 × 7 Gy | N(p) + N(Ao) − | 2 weeks | 24 pulmonary Metastasis |
---|---|---|---|---|---|---|---|---|---|---|
10 (2010) | 32 | 10 | spontaneous metrorrhagia + loss whitish | Moderately differentiated squamous | >4 | IB2 | 1) TIP, concomitant radio-chemotherapy 46 Gy, 2 Gy/fr + cisplatin 40 mg/m2 and brachytherapy LDR 24 Gy | No lymphadenectomy | 3 weeks | 24 |
Note: IIBproxi: IIB proximal; ADK: adenocarcinoma; LDR: low dose rate; HDR: high dose rate; IFOG: International Federation of Obstetrics Gynecology; TIP: therapeutic interruption of pregnancy; N (p) +: positive pelvic lymph node; N (Ao) −: negative paraaortic lymph node; WG: week of gestation.
Toxicity:
Acute side effects have been registered; it was grade 2 radiodermatitis in two cases, and diarrhea in three cases. These side effects have been treated symptomatically.
After 4 years median follow up (2 - 7), the local control rate was 100%. The overall survival rate was 100%. Bone and lung metastasis occurred at 2 years in patient N˚ 9.
The diagnosis of cervical cancer can be done by clinical signs. Spontaneous or post-coital metrorrhagia was observed in 43% to 54% of patients at early stages and in 81% of patients at advanced stages [
It is well known that ionizing radiation is deleterious to the fetus [
Regarding the management of pregnancy, Maurice et al. recommendations [
• If the tumor is diagnosed at a term when fetal maturity could be considered attained
It is possible to preserve the fetus without delaying the treatment of the cervical cancer that should be performed, according to the standards of care, after the delivery. The term of delivery should be defined according to the term at the time of the diagnosis and to whether the tumor needs to be treated urgently (stage of the disease and tumor size). The delivery should be (optimally) performed using a cesarean section [
During this cesarean section, nodal staging surgery (pelvic nodes with or without paraaortic nodes for tumors greater than 4 cm or positive pelvic nodes) is recommended. Such staging procedure needs to be carried out by surgeons experienced in performing this oncologic surgical procedure. Ideally, the obstetrician and gynecologic oncologist should be present during this cesarean section.
In multiparous women and in patients who do not wish to preserve their fertility, with stage IB1 disease, a radical hysterectomy can be associated with nodal surgery at the time of the cesarean section [
• If the tumor is diagnosed before the term when fetal maturity is attained (between 26 and 30 WG) in a patient wishing to preserve the fetus (tumor with a usual histological subtype and exclusion of small cell carcinoma or a similar aggressive tumor).
√ Stage IB1 disease diagnosed before 18 to 22 WG (term when pelvic laparoscopic lymphadenectomy is still technically feasible).
➢ Stage IB1 and tumor size less than 2 cm
The pregnancy is not being interrupted at this point. An initial laparoscopic pelvic lymphadenectomy is recommended [
*Absence of nodal involvement: In this case, the patient is followed up without immediate treatment of the cervical tumor. This follow-up procedure should include a clinical examination and imaging (MRI every 4 to 8 weeks, but there is no consensus among experts concerning the frequency of MRI) [
*Presence of nodal involvement: In this case, interruption of the pregnancy should be recommended to the patient, and the standard management is chemoradiation therapy (after the uterus is empty). The radiation therapy fields depend on the highest level of nodal involvement (pelvic nodes alone or pelvic and paraaortic nodes). The status of paraaortic nodes can be determined by performing a laparoscopic paraaortic lymphadenectomy or positron emission tomography imaging (carried out after pregnancy interruption). The choice between these 2 procedures will depend on the team administering treatment and on whether the surgeons have experience with laparoscopic paraaortic lymphadenectomy.
➢ Stage IB1 disease with a tumor size between 2 and 4 cm
It is impossible to define a standard management policy in such a situation, and each case should be discussed separately. The risk of nodal involvement is significantly higher than in patients with a tumor measuring less than 2 cm so pregnancy interruption is the first option that should be discussed with the patient (particularly if the tumor is discovered during the first trimester). If the patient refuses this option, management could be similar to that of patients with a tumor measuring less than 2 cm.
√ In stage IB1 disease diagnosed after 18 to 22 WG (for which laparoscopic lymphadenectomy is not technically feasible, even in the hands of experienced surgeons).
➢ Stage IB1 and tumor size less than 2 cm
Careful follow-up should be conducted including clinical and radiological imaging (in the absence of suspicious lymph nodes on initial imaging). The clinician should explain to the patient the oncologic uncertainty in such a situation, namely, the potential risk of increasing the recurrence rate while awaiting fetal maturity. Curative treatment of the cervical tumor should be initiated once fetal maturity has been attained. The presence of a malignant tumor is not a contraindication to the use of neonatal corticoids to increase fetal chest maturity.
The delivery route should be a cesarean section, and the cervical tumor should be treated according to the standards of care. A radical hysterectomy with pelvic lymphadenectomy can be performed at the time of cesarean section.
➢ Stage IB1 with a tumor size between 2 and 4 cm
It is impossible to define a standard management policy in such a situation; therefore, each case should be discussed individually. If the term when the tumor is diagnosed is very close to the term when fetal maturity is attained, the management can be similar to that of patients with a tumor measuring of less than 2 cm.
Particularly if the tumor size is close to 4 cm, the other option that could be discussed is the use of neoadjuvant chemotherapy (confers chapter neo adjuvant chemotherapy). However, the patient should be informed of the uncertainty regarding the oncologic and fetal outcomes of such management.
➢ Patients with tumor greater than 4 cm
The standard management in France in such patients is based on chemoradiation therapy. If the tumor is discovered before 20 to 22 WG (no consensus between experts regarding this term), chemoradiation therapy should be delivered either after the uterus is empty (using a hysterotomy or another procedure [
If the tumor is diagnosed after 22 WG (in the absence of extra cervical spread detected at the radiological examination), chemoradiation can be started after the caesarean delivery, which should be performed once fetal maturity has been attained (provided such management will not delay the start of tumor treatment for >6 - 8 weeks). During this caesarean section, paraaortic staging surgery is recommended (if such surgery is performed by a surgeon who has experience performing this procedure).
Another option could be discussed in such situation in patients wishing to preserve the viability of their fetus: the use of neoadjuvant chemotherapy. It should be discussed only if the tumor is diagnosed after 18 to 20 WG. The patient should receive a clear explanation regarding the potential risk of rapid progression (potentially lethal for the patient) of the disease reported in several cases after such management in the literature [
• Patients with more aggressive histological subtype (small cell carcinoma or a similar unusual tumor) diagnosed during the first or second trimester of pregnancy.
In such situation, each case should be discussed individually, but pregnancy preservation is not recommended because treatment of the tumor is regarded as an oncologic emergency.
Therapeutic option for maintaining pregnancy
Neoadjuvant chemotherapy in advanced cervical cancer causes the regression of tumor size and is considered a promising technique in curative management [
Tewari et al., in 1997, presented two cases treated with vincristine and cisplatin during pregnancy at 34 and 36 WG, with stages IIA and IB respectively [
Data from the cisplatin exposure literature during pregnancy are also very low. Out of 21 reported cases, two had intrauterine growth retardation; a patient had bilateral partial deafness, and one last patient had idiopathic ventricular dilatation with neurologic sequeals [
Diagnosis-treatment time is the time elapsed in weeks between the diagnosis of cervical cancer and the main treatment; this delay is one of the main points to consider. In our series the median time was 3 weeks (2 to 8). Karam et al., in 2007 listed all published studies concerning treatment postponement times for patients with invasive cervical cancer diagnosed during pregnancy and wishing to continue the pregnancy, delays ranged from 3 to 40 weeks [
Some retrospective studies [
In our series, the diagnosis was made in regional centers of gynecology; under duress, the initial therapeutic attitude did not often meet the recommendations (desire of the couple not to maintain the pregnancy and tumor size > 5cm). All patients were referred for further management.
Our series focused on ten patients with invasive cervical cancer during pregnancy. Management is complex and requires discussion in a multidisciplinary meeting. Routine screening of cervical cancer and awareness are the key point to improve the treatment and survival rate of patients. The management of all cases isaccording to international recommendations.
As per international standard or university standard, patient’s written consent has been collected and preserved by the authors.
All authors hereby declare that all experiments have been examined and approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
Authors have declared that no competing interests exist.
Diabaté, K., Bakkali, H., Lachgar, A., Nadir, S., Kebdani, T., El Gueddari, B.K. and Benjaafar, N. (2018) Management of Pregnant Women with Invasive Cervical Cancer about Ten Cases. Journal of Cancer Therapy, 9, 740-754. https://doi.org/10.4236/jct.2018.99061