Author
Information
Karve N*, Gupta AS**.
(* Fourth Year Resident, ** Professor. Department of Obstetrics and Gynecology, Seth G. S. Medical College and KEM
Hospital , Mumbai , India
Abstract
A 25
year old gravida 3 para 2 living 1 and intrauterine fetal death (IUFD) 1 with
twin gestation and tobacco addiction was diagnosed with carcinoma cervix in the
second trimester. She had been referred to a tertiary level oncology center but
had poor follow-up there. She presented to our center at 36 weeks with twin gestation and preterm premature
rupture of membranes (PPROM). An
emergency classical cesarean section was performed. She was stage 1B2 (bulky)
carcinoma of the cervix. Her postoperative period was uneventful. She was
referred for definitive treatment to an oncology center.
Introduction
Genital
malignancies are rarely associated with pregnancy, the incidence estimated to
be about 1/1000.[1] However, carcinoma cervix remains the most common genital
malignancy associated with pregnancy, second only to carcinoma breast (46%) and
hematological malignancies (18%) in overall incidence [2].
Lack
of awareness regarding timely antenatal registration and routine Pap smear
screening for cervical dysplasia often leads to patients presenting with
advanced stages of cancer and late into the pregnancy. The obstetrician and
gynecologist then face the challenge of balancing the well-being of the mother
and the fetus. This case report attempts to highlight the major aspects of
managing a patient with advanced stage carcinoma cervix in pregnancy.
Case
Report
Our
patient was 25 year old gravida 3 para 2 living 1 and IUFD 1 with twin
gestation. After repeated episodes of painless vaginal bleeding and leucorrhea
in the mid trimester at 20 weeks of gestation she underwent a cervical biopsy
at a peripheral hospital in Gujarat. The histopathological diagnosis was a
large cell non-keratinizing squamous cell carcinoma, after which she was
referred to a tertiary level oncological center for further management. She
paid a single visit there at which time her clinical stage was determined to be
I B2 and she was advised further investigations like magnetic resonance imaging
(MRI), which she did not get done, nor did she follow up there again. She came
to our casualty twice, earliest at 30 weeks and refused admission on both the
occasions. The patient was referred to the Tata Memorial cancer center in
Mumbai. She visited the center once and was staged as carcinoma cervix 1B2. She
was advised MRI and follow up. She neither got the MRI done nor did she follow
up. She presented to us at 36 weeks gestation in labor and PPROM for one day.
Uterus was over distended and two fetal heart sounds were heard. On speculum
examination frank clear leak was seen along with an irregular friable fungating
growth which had replaced both the lips of the cervix of about 4 X 5 cm size. The external os was obscured by the mass. The
portio vaginalis was entirely replaced by the mass. However, the upper and the
lower vaginal walls did not show any tumor deposits. The mass showed slight
bleeding and profuse foul smelling discharge. Vaginal examination was not done
due to the fear of precipitating torrential hemorrhage. Rectal mucosa was free.
The
patient was admitted and all laboratory investigations were sent. Her Hb was
8.1 g/dl for which she was transfused with one unit of packed red blood cells
perioperatively. She was found to be VDRL reactive with a titre of 1:16. Her PT
was 12/11.5 and INR was 0.58. After anesthesia fitness and high risk consent
the patient was taken up for classical cesarean section.
Figure
1: Classical cesarean section
Two
healthy male babies weighing 2 kg each were delivered with Apgar scores 9/10
each at birth. Intraoperatively there was no palpable mass or growth in the
lower uterine segment or in the adnexa. Patient’s postoperative period was
uneventful. The babies were screened for neonatal syphilis, were found to be
negative and were advised follow-up after 6 weeks for repeat serum titers. The
mother’s repeat VDRL titrer was also negative. The patient was kept in the ward
for extended period till complete suture removal after which the wound was
healthy. The patient was counseled regarding her illness, its prognosis and
need for aggressive and complete treatment. She was advised to follow up at our
center as well as the oncology center for chemoradiation therapy after
discharge. She has not followed up at our institution and multiple attempts to
contact her have been unsuccessful.
Discussion
The
management of cervical cancer in pregnancy spans the full range of cervical
neoplasia and treatment depends on the stage of the disease and gestational age
at presentation. The patient’s desire to continue the pregnancy might produce a
challenge for the gynecologist and meticulous counseling is necessary before
the patient takes an informed decision. Nevertheless, when a diagnosis is reached
in the first trimester delaying treatment poses significant risk to maternal
prognosis.[3]
Screening
for carcinoma cervix in high-risk populations is recommended but ideally all
antenatal patients must undergo routine speculum examination at first visit
since symptoms of pregnancy and carcinoma may be overlapping. Identification of
high-risk factors like tobacco use (as in above patient) must be searched for
at the first antenatal visit. Nevertheless as many as 8% patients may be
diagnosed with carcinoma cervix without any suspicious symptoms.[4]
Clinical
staging might be difficult because of inadequate per vaginal examination and
hence examination under anesthesia might be a suitable option. However, FIGO
staging of cervical cancer is still a clinical staging even in pregnant
patients.[5] Evaluation of a suspicious cervical lesion can be done by
colposcopy, punch biopsy, conization, and/or non-invasive techniques like MRI
or ultrasonography. The deleterious effects of Gadolinium contrast on the fetus
is as yet undetermined.
After
a diagnosis has been attained the patient and spouse need to be counseled about
their treatment options. They may be desirous of continuing the pregnancy, but
should be explained that delaying treatment for more than 8 weeks in order to
achieve fetal maturity is unacceptable.[5]
The
importance of managing a carcinoma cervix patient at a specialized center
cannot be over-emphasized. A team consisting of gynecological oncologist,
medical oncologist, radiotherapist and neonatologist is essential in order to
do justice to both mother and baby. [6] Vaginal delivery is acceptable only in
patients with pre-invasive disease or those planning post-partum
fertility-preserving surgery. All other patients must deliver by cesarean
section with concomitant radical surgery depending on the stage of the disease.
Fetal pulmonary maturity must be confirmed before surgery.[7] Classical
cesarean incision is preferred and concomitant ovario-pexy must be done in view
of future radiotherapy.[7] The classical cesarean section prevents the risk of
torrential vaginal bleeding, cervical tears and lacerations and risk of
lympho-vascular dissemination of the cancer cells that can occur with vaginal
birth.[2] Considering the young age of these patients, surgical management is
preferable to radiotherapy, if feasible, depending on the stage of the disease
because of the added advantages of ovarian preservation and preventing
radiation-induced vaginal fibrosis. Stages of carcinoma of stage IB1 and tumor
size > 2 cm neo-adjuvant chemotherapy can be given till fetal maturity is
achieved. Paclitaxel with carboplatin or cisplatin is the preferred treatment
considering the tolerance and toxicity profile.[8] The algorithm recommended
for management of pregnant women with cervical carcinoma of stage IB1 and >
4 cm in size is to perform pelvic lymph node dissection and pelvic and aortic
lymph node dissection and to give them neoadjuvant chemotherapy even if the
nodes are negative.[9] However, if the nodes are positive in pregnancy the
pregnancy should be terminated irrespective of the gestational age as the risk
of disease progression is high.[9]
It
was unfortunate that our patient was a defaulter. Despite being diagnosed,
counseled and referral to an oncology center prior to 20 weeks she did not
persist in her definitive treatment. Her management misses were many. She could
have undergone definitive treatment most likely radical hysterectomy with
pelvic lymphadenectomy at 20 weeks of gestation at the oncology center in Gujarat
after her biopsy diagnosed the lesion. However, she did not complete her
treatment. She again lost two opportunities for admission and delivery at 32
weeks of gestation after administration of steroids for fetal lung maturity and
subsequent definitive management. She
did not get the MRI done as advised by the second oncologist at Tata Memorial
hospital. A course of cisplatin and paclitaxel
every 3 weeks for 6 cycles as neoadjuvant chemotherapy could have aided
in the shrinkage of the tumor while awaiting fetal lung maturity and delivery.
The recommendation of this platinum based chemotherapy is based on small case
reports or case series.[9] The neoadjuvant therapy should be avoided in the
third trimester as delivery within less than 3 weeks after completion of the
course is not recommended as the placenta does not get sufficient time to
metabolize and eliminate the drug received by the fetus and also the maternal
bone marrow does not have adequate time to recover from the side effects of the
chemotherapy. However, she also did not receive any neoadjuvant chemotherapy
for the above reasons. She was always accompanied by her 14 year old son. Her
husband was negligent towards her health and she was apathetic towards her own
health. Her emergency admission in labor
was unfortunately on a weekend wherein MRI could not be performed and the
proper staging in a suspected Stage 1B2 bulky lesion could not be ascertained.
Classical cesarean delivery however was performed and her twins were delivered.
Considering that the patient was only 25 year old, had she been properly staged
a radical cesarean hysterectomy with pelvic lymphadenectomy could have been
considered as a definitive treatment. However, since the lesion was clinically
staged as IB2 bulky, and the absence of an MRI the decision was taken to refer
the patient to the oncology center for proper staging and chemoradiation after
suture removal. The couple was counseled to take treatment from the oncologist
but sadly she has not done so and also she is not contactable.
Conclusion
Frequent
pregnancies, failure to grasp the gravity of the situation, neglecting woman’s
health issues are common features in the
developing nations. Timely staging, use of neoadjuvant chemotherapy in
pregnancy, close watch to detect progression of the disease, giving definitive
treatment if disease progress is witnessed, avoiding vaginal birth in all cases
except preinvasive and microinvasive lesions, performing classical cesarean
births after fetal lung maturity and performing radical hysterectomy with
pelvic lymphadenectomy along with classical cesarean sections in stage IA and
IB1 lesions, referring the other stages for chemoradiation after childbirth can help in individualizing and
strategizing the treatment of carcinoma cervix that is detected in pregnancy.
References
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Karve N, Gupta AS.