Background
Cervical cancer is the most common gynecological cancer in pregnancy, with an estimate
of 0.1-12 per 10,000 pregnancies. For cervical intraepithelial neoplasia, incidence
rates range from 1.3 to 2.7 per 1,000.[1]
[2]
[3] Studies have not shown differences in the oncological prognosis of women with cervical
cancer diagnosed during pregnancy compared to that in non-pregnant women.[1]
[2]
[3] The growing number of pregnant patients treated for a neoplasm and the follow-up
of children resulting from these pregnancies generate safety in the use of various
chemotherapy drugs during pregnancy. This has reflected in a greater number of pregnancies
carried to term and better neonatal and neuropsychomotor development outcomes for
these children.[1]
[3]
What is the conduct related to the pregnant patient with altered Pap smear?
Screening for pre-neoplastic lesions and cervical cancer in pregnant women should
be performed using colpocytology following the recommendations for periodicity and
age range for non-pregnant women. Visiting a health service for antenatal care should
always be considered as an opportunity for screening.[1]
[4] Patients with altered cervical cytology should be referred for colposcopy. There
is no contraindication for performing a biopsy at any stage of pregnancy.[4] In patients with a histological diagnosis of CINII or CINIII, treatment should be
postponed until after delivery, given the minimal risk of neoplastic progression during
pregnancy. Follow up with colposcopy every 12 weeks should be carried out. The biopsy
should be repeated only if invasion is suspected. Diagnostic conization is indicated
in pregnancy only if staging or confirmation of residual invasive disease change the
timing and type of delivery. Otherwise, this procedure should be postponed to the
postpartum period.
What is the management of pregnant patients with a suspected lesion of invasive cervical
neoplasia?
Suspicious cervical lesions in pregnant patients should be investigated through incisional
biopsy. After confirmation of malignancy, imaging staging should preferably be performed
using chest X-ray with abdominal protection and magnetic resonance imaging of the
entire abdomen without contrast, considering that gadolinium is associated with rheumatological
diseases in children and neonatal death. When magnetic resonance imaging is not available,
an ultrasound of the entire abdomen can be performed with emphasis on the kidneys
and urinary tract.[1]
[3]
[5]
Which centers are able to manage patients with cervical cancer diagnosed during pregnancy?
These patients should be treated in a reference center with a multidisciplinary team
(oncological gynecologists, clinical oncologists, obstetricians specializing in high-risk
pregnancies, neonatologists, radio-oncologists and psychologists). Treatment depends
on staging, gestational age and the desire to preserve the pregnancy, always on an
individual basis and after multidisciplinary discussion, taking into account the risks
of postponing or modifying the treatment for that patient.
Is it possible to legally terminate pregnancy in pregnant patients with cervical cancer?
It is impossible to carry out standard therapy for cervical cancer (radical surgery
and/or pelvic radiotherapy) and maintain the pregnancy. Therefore, the termination
of pregnancy up to 22 weeks in patients with cervical cancer is provided for in article
128 of the Brazilian Penal Code (necessary or therapeutic abortion when there is a
risk to the mother's life)[6] and by Ordinance GM/MS number 1.508 from the Ministry of Health.[7] After this gestational age, the fetus is considered viable in most centers and the
management must be individualized. Termination of pregnancy followed by standard oncologic
treatment is recommended in patients with locally advanced disease or with positive
lymph node. In this context, patients who choose to continue with the pregnancy should
be informed they will not undergo standard oncological treatment, which could result
in compromised maternal prognosis and increased obstetric risks.[1]
[3]
How should pregnancy be terminated?
For termination of pregnancy in patients with cervical cancer, the following are required:
-
The evaluation of at least two professionals; one of them must be a specialist in
the disease causing the interruption:
-
Medical record with medical justifications detailing the maternal risk;
-
The consent and/or informed consent signed by the pregnant woman or her family, unless
this is impossible in situations of imminent risk to her life;
-
Support and monitoring by a multidisciplinary team, especially psychologists.
Judicial authorization, police reports or communication to the Regional Council of
Medicine are not required. The method of termination of pregnancy depends on gestational
age and staging. In patients with early-stage disease, a radical hysterectomy can
be performed with the fetus in situ. In locally advanced disease during the first
trimester, abortion with evacuation of the conceptus is indicated. When surgical abortion
is not feasible given the presence of a tumor obliterating the cervical OS, radiotherapy
can be started with the intrauterine conceptus. This results in a miscarriage within
three weeks.[1]
[3] Over 16 weeks, preference is given to feticide before starting treatment or evacuation.
How should be the management of pregnant patients with stage IA1 or IA2 cervical cancer?
Conservative surgical treatment, such as conization, is recommended preferably between
14 and 22 weeks. After this gestational age, due to the risk of bleeding and pregnancy
loss, quarterly surveillance should be carried out with colposcopy until delivery,
and definitive treatment six weeks after delivery. Conization with high-frequency
surgery is associated with less bleeding and complications.[1]
[8] The indication for cerclage is controversial.
What is the role of lymphadenectomy in pregnant patients with cervical cancer?
Lymph node metastasis is one of the main prognostic factors in cervical cancer. For
this reason, some authors advocate performing staging lymphadenectomy to truly determine
the staging and prognosis and therefore, better select the candidates to continue
the pregnancy. It is feasible up to 20 weeks, since after this gestational age, the
uterine volume compromises the surgical field and the number of resected lymph nodes
drops considerably, hence it is not considered appropriate for staging purposes.[1]
[3] The route of choice is laparoscopic in experienced hands, as it is associated with
faster recovery and better postoperative pain control. Sentinel lymph node screening
is not recommended in pregnant women given the risk of patent blue anaphylaxis and
the lack of safety data with the use of technetium and indocyanine green during pregnancy.
In case of positive lymph nodes, the tendency is to interrupt the pregnancy to allow
standard treatment. Patients who refuse the interruption should be advised to undergo
treatment with neoadjuvant chemotherapy performed until three weeks before delivery.
How should be the management of pregnant patients up to 20 weeks and cervical cancer
stages IB1 and IB2?
Several studies in patients with cervical cancer have shown a negligible risk of parametrial
involvement when the pelvic lymph nodes are negative.[9] Therefore, by taking into account the significant morbidity of radical trachelectomy
during pregnancy, such as pregnancy loss and bleeding, there is support in the literature
to manage these patients with pelvic lymphadenectomy and wide conization or simple
trachelectomy to obtain free margins, followed by cerclage. A multidisciplinary team,
including radiologists, should perform the surgical planning with the aim of assessing
the chance of resection of tumor free margin, maintaining a safe distance from the
internal cervical os. In cases when a free-margin conization is not feasible, surgery
is not recommended.
How should be the management of pregnant patients over 20 weeks and diagnosis of cervical
cancer stages IB1 and IB2?
The case series study of patients with a diagnosis of cervical cancer restricted to
the cervix at the end of the second trimester and in the third trimester, who underwent
expectant management with surveillance of progression showed excellent oncological
outcomes, hence this treatment is an option.[8] In patients diagnosed at the beginning of pregnancy, or when expectant management
is not considered prudent due to other prognostic factors (deep stromal invasion,
angiolymphatic invasion or unfavorable histological types), neoadjuvant chemotherapy
with carboplatin and paclitaxel is indicated every three weeks, starting after 14
weeks of pregnancy. If there is no progression, treatment should be carried out until
34/35 weeks to allow for full-term delivery. Given the risk of maternal and neonatal
complications, such as infection and hemorrhage, chemotherapy should be discontinued
three weeks before the planned date of delivery.[1]
[3]
How should be the management of pregnant patients with locally advanced tumor who
wish to preserve the pregnancy?
Neoadjuvant chemotherapy with carboplatin and paclitaxel is indicated every three
weeks, starting after 14 weeks of pregnancy. If there is no progression, treatment
should be performed until 34/35 weeks and delivery at term.[10] Radiochemotherapy can be started two weeks after delivery.[1]
[3]
How should be the management of pregnant patients with stage IVB cervical cancer?
Palliative chemotherapy may be offered. Immunotherapies with recombinant humanized
monoclonal antibodies such as bevacizumab and pembrolizumab are contraindicated during
pregnancy.[1]
[2]
[3] Early referral to palliative care for control of pain and other symptoms is fundamental
in the context of advanced and metastatic disease, contributing not only to improve
the quality of life, but also to increase the survival of these patients.
How should birth planning be in pregnant patients with cervical cancer?
In cases in which there is no progression of the disease or obstetric indication of
anticipation of delivery, the ideal moment of delivery should be at the term of pregnancy.
The mode of delivery is cesarean section when there is invasive cervical disease,
with a corporal cesarean section to avoid the risk of extending the hysterotomy to
the cervix and the consequent tumor laceration, with contamination of the abdominal
cavity.[1]
[3] Vaginal delivery is contraindicated in patients with invasive cervical cancer, as
it poses maternal and fetal risk. In addition to the risk of tumor bleeding and obstruction
of the birth canal, the literature describes 20 cases of implantation in a laceration
of the birth canal or episiotomy with a fatal outcome in most cases.[1]
[3] Arakawa et al.[11] reported two cases of children who developed squamous cell carcinoma of the lung
after vaginal delivery in a patient with the same neoplasm in the uterine cervix.
In patients treated with free-margin conization and without evidence of cervical disease,
the mode of delivery is obstetric.[1]
[3]
How should definitive treatment be performed after childbirth?
The definitive treatment will depend on the patient's reproductive desire.
Patients with reproductive desire:
Patients without reproductive desire:
-
Patients with surgical treatment indication: Extrafascial or radical hysterectomy
and pelvic lymphadenectomy can be performed right after the cesarean or six weeks
later. The decision regarding the best moment for definitive surgical treatment must
be individualized, taking into account the tumor biology, the patient's surgical risk
and the surgeon's experience. Hysterectomy right after cesarean is associated with
increased blood loss and perioperative complications, such as surgical wound infection
and urinary tract infection. [12] In addition, sentinel lymph node biopsy is not feasible in this scenario. Waiting
six weeks after delivery could allow this less morbid lymph node evaluation.
-
Patients with indication of chemoradiotherapy can start treatment two weeks after
delivery
Final considerations
The concomitant diagnosis of cancer and pregnancy is a rare and dramatic situation.
The medical literature is limited to case series and a consensus of the European Society
of Gynecological Oncology/European Society for Medical Oncology (ESGO/ESMO); guidelines
must always be interpreted with caution. Multidisciplinary and individualized evaluation
is the best way to ensure the best outcome for the mother and, when there is a desire
to preserve the pregnancy, for the fetus.
National Commission Specialized in Gynecologic Oncology of the Brazilian Federation
of Gynecology and Obstetrics Associations (Febrasgo)
President:
Walquíria Quida Salles Pereira Primo
Vice-president:
Suzana Arenhart Pessini
Secretary:
Jesus Paula Carvalho
Members:
Angélica Nogueira Rodrigues
Caetano da Silva Cardial
Delzio Salgado Bicalho
Eduardo Batista Candido
Etelvino de Souza Trindade
Fernando Maluf
Francisco José Cândido dos Reis
Georgia Fontes Cintra
Marcia Luiza Appel Binda
Mirian Helena Hoeschl Abreu Macedo
Renato Moretti Marques
Ricardo dos Reis
Sophie Françoise Mauricette Derchain
Heloisa de Andrade Carvalho
Filomena Marino Carvalho
Aline Evangelista Albuquerque
Leandro Santos de Araújo Resende
