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Management during Pregnancy

There is no difference in survival between pregnant and nonpregnant women with cervical
cancer when matched by age, stage, and year of diagnosis. As with nonpregnant women, clinical
stage at diagnosis is the single most important prognostic factor for cervical cancer during
pregnancy. Overall survival is slightly better for cervical cancer in pregnancy because an
increased proportion of patients have stage I disease.
A Pap smear is recommended for all pregnant patients at the initial prenatal visit. Additionally,
clinically suspicious lesions should be directly biopsied. If Pap test results reveal HSIL or
suspected malignancy, then colposcopy is performed and biopsies are obtained. However,
endocervical curettage is excluded. If Pap testing indicates malignant cells and colposcopicdirected biopsy fails to confirm malignancy, then diagnostic conization may be necessary.
Conization is recommended only during the second trimester and only in patients with
inadequate colposcopic findings and strong cytologic evidence of invasive cancer. Conization is
deferred in the first trimester, as this surgery is associated with abortion rates of 30 percent in this
part of pregnancy.
Stage I Cancer in Pregnancy
Women with microinvasive squamous cell cervical carcinoma measuring 3 mm or less and
containing no LVSI may deliver vaginally and be re-evaluated 6 weeks postpartum. Moreover,
for those with stage IA or IB disease, studies find no increased maternal risk if treatment is
intentionally delayed to optimize fetal maturity regardless of the trimester in which the cancer
was diagnosed. Given the outcomes, a planned treatment delay is generally acceptable for
women who are 20 or more weeks' gestational age at diagnosis with stage I disease and who
desire to continue their pregnancy. However, a patient may be able to delay from earlier
gestational ages if she wishes.
Advanced Cervical Cancer in Pregnancy
Women with advanced cervical cancer diagnosed prior to fetal viability are offered primary
chemoradiation. Spontaneous abortion of the fetus tends to follow whole-pelvis radiation
therapy. If cancer is diagnosed after fetal viability is reached and a delay until fetal pulmonary
maturity is elected, then a classical cesarean delivery is performed. A classical cesarean incision
minimizes the risk of cutting through tumor in the lower uterine segment, which can cause
serious blood loss. Chemoradiation is administered after uterine involution. For patients with

advanced disease and treatment delay, pregnancy may impair prognosis. Women who elect to
delay treatment, to provide quantifiable benefit to their fetus, will have to accept an undefined
risk of disease progression.


Cervical Cancer during Pregnancy
The incidence of invasive cervical cancer associated with pregnancy is 1.2 in 10,000 (157). A
Pap test should be performed on all pregnant patients at the initial prenatal visit, and any grossly
suspicious lesions should be biopsied. Diagnosis is often delayed during pregnancy because
bleeding is attributed to pregnancy-related complications. If the result of the Pap test is
positive for malignant cells, and invasive cancer cannot be diagnosed using colposcopy and
biopsy, a diagnostic conization procedure may be necessary. Conization in the first
trimester of pregnancy is associated with an abortion rate as high as 33% (158,159), as well
as hemorrhagic and infectious complications. Because conization subjects the mother and
fetus to complications, it should be performed only in the second trimester and only in
patients with colposcopy findings consistent with cancer, biopsy-proven microinvasive
cervical cancer, or strong cytologic evidence of invasive cancer. Inadequate colposcopic
examination may be encountered during pregnancy in patients who have had prior ablative
therapy. Close followup throughout pregnancy may allow the cervix to evert and develop an
ectropion, allowing satisfactory colposcopy in the second or third trimester. Patients with
obvious cervical carcinoma may undergo cervical biopsy and clinical staging similar to that of
nonpregnant patients.
After conization, there appears to be no harm in delaying definitive treatment until
fetal maturity is achieved in patients with stage Ia cervical cancer (158,160,161). Patients
with less than 3 mm of invasion and no lymphatic or vascular space involvement may be
followed to term. Historically, these patients were allowed to deliver vaginally, and a
hysterectomy was performed 6 weeks postpartum if further childbearing was not desired.
However, in a multivariate analysis of 56 women with cervical cancer diagnosed during
pregnancy and 27 women with cervical cancer diagnosed within 6 months of delivery, vaginal

delivery was the most significant predictor of recurrence (162). In addition, most recurrences
after vaginal delivery involved distant sites. The ideal delivery method for these patients is not
known definitively; however, strong consideration should be given to performing a cesarean
birth in women with cervical cancer of any stage (162). If vaginal delivery is chosen, close
inspection of the episiotomy site is required during follow-up because of rare reports of
metastatic cervical cancer at these locations (163).
Patients with 3 to 5 mm of invasion and those with lymphvascular space invasion may
also be followed to term or delivered early after establishment of fetal pulmonary maturity
(158,161). They may be delivered by cesarean birth, followed immediately by modified radical
hysterectomy and pelvic lymphadenectomy. Patients with more than 5 mm invasion should be
treated as having frankly invasive carcinoma of the cervix. Treatment depends on the
gestational age of the pregnancy and the wishes of the patient. Modern neonatal care affords a
75% survival rate for infants delivered at 28 weeks of gestation and 90% for those delivered at
32 weeks of gestation. Fetal pulmonary maturity can be determined by amniocentesis, and
prompt treatment can be instituted when pulmonary maturity is documented. Although timing is
controversial, it is probably unwise to delay therapy for longer than 4 weeks (160,161). The
recommended treatment is classic cesarean delivery followed by radical hysterectomy with
pelvic lymph node dissection. There should be a thorough discussion of the risks and options
with both parents before any treatment is undertaken.
Patients with stage IIIV cervical cancer should be treated with radiotherapy. If the
fetus is viable, it is delivered by classic cesarean birth, and therapy is begun
postoperatively. If the pregnancy is in the first trimester, external radiation therapy can be
started with the expectation that spontaneous abortion will occur before the delivery of 4,000
cGy. In the second trimester, a delay of therapy may be entertained to improve the chances of
fetal survival. If the patient wishes to delay therapy, it is important to ensure fetal pulmonary
maturity before delivery is undertaken.
The clinical stage is the most important prognostic factor for cervical cancer during
pregnancy. Overall survival is slightly better because an increased proportion of these patients

have stage I disease. For patients with advanced disease, there is evidence that pregnancy impairs
the prognosis (158,161). The diagnosis of cancer in the postpartum period is associated with a
more advanced clinical stage and a corresponding decrease in survival (162).

Carcinoma of the Cervix in Pregnancy
Rarely, an invasive carcinoma of the cervix is discovered in a pregnant patient. Within each
stage, survival statistics are similar in pregnant and nonpregnant women. A concern has been that
the delivery of a fetus through a cervix replaced by carcinoma might worsen the prognosis due to
tumor dissemination, but there is no clear evidence to indicate that tumor dissemination is caused
by the birth process. However, tumor recurrence in episiotomy sites following vaginal delivery
has been reported by Cliby and associates. The major risk to the patient of delivery through a
cervix containing invasive carcinoma is the risk of hemorrhage as a result of tearing of the tumor
during cervical dilation and delivery.
A problem arising in pregnancy is whether a patient with an abnormal cytologic smear has
intraepithelial neoplasia or invasive cancer. In general, if the cytologic and histologic findings of
colposcopically directed biopsies are comparable and suggest intraepithelial neoplasia or
carcinoma in situ, the patient is observed and delivered, with final evaluation and therapy
completed approximately 6 weeks after delivery. Even if there is a question of microinvasion, a
patient so diagnosed in the last trimester of pregnancy is usually followed and evaluated further
after de-livery. Cervical conization during pregnancy can lead to severe complications,
particularly hemorrhage and also loss of the fetus. If it is necessary to perform a conization or
preferably a wedge resection of the cervix during pregnancy, it is probably best to perform this
during the second trimester, when the risks of fetal loss and hemorrhage are minimal. For
patients in whom invasive cancer is diagnosed, a therapeutic plan must be developed to deliver
appropriate care, with regard also for the outcome of the pregnancy.
The therapy of carcinoma during pregnancy is influenced by the stage of the disease, the time in
pregnancy the cancer is diagnosed, and the beliefs and desires of the patient in terms of initiating
therapy that can terminate the pregnancy as opposed to postponing the therapy until fetal

viability is achieved. If carcinoma is diagnosed in the first trimester or early in the second
trimester (before 20 weeks), treatment may be undertaken immediately because of the concern
that a delay could lead to tumor progression or spread. However, Duggan and colleagues had
delays of 2 to 7 months in eight pregnant patients with stage I disease and demonstrated no
adverse effects from the delay. If the patient has resectable tumor (stage IB or early IIA), then
effective treatment consists of radical hysterectomy and node dissection (class III). This
procedure can usually be carried out without difficulty on a pregnant woman. Increased uterine
motility and edema of the pelvic tissue planes help to simplify the procedure for the experienced
surgeon, but pregnancy does increase the risk of blood loss. For higher stage tumors, therapy is
begun with external beam radiation (teletherapy), and usually in 4 to 6 weeks, this leads to
spontaneous abortion. The dose of external therapy prescribed varies depending on the stage of
the tumor, but approximately 40 to 50 Gy is given. Although the results of a published series are
not available, it would appear preferable to augment the radiation with weekly cisplatin because
the pregnancy in this instance would be terminated. Following abortion, the uterus involutes, and
an implant (brachytherapy) is placed. If the pregnancy does not spontaneously abort, dilation and
curettage, prostaglandin-assisted delivery, or, rarely, hysterotomy may be necessary to empty the
uterus before brachytherapy. Alternatively, if the initial tumor was small and has completely
regressed, an extrafascial hysterectomy or modified radical hysterectomy may be performed.
For patients beyond the 20th week of gestation, therapy is often delayed until fetal viability. The
health and maturity of the fetus are determined by appropriate ultrasound studies and amniotic
fluid analysis to ensure fetal lung maturity. Delivery is usually accomplished by cesarean section,
and after this, therapy is completed by surgery or radiation with the usual considerations of
tumor stage and size. Overall, treatment results in pregnant patients are similar to those in
nonpregnant patients, stage for stage, as recently confirmed by van der Vange and coworkers.
The reader should be aware that many published studies dealing with carcinoma of the cervix in
pregnancy include cases treated as long as 1 year postpartum, which assumes the carcinoma was
present during pregnancy. Hacker and associates summarized the results of 1249 cases reported
in various series in the literature. Overall, a 5-year survival rate of 49.2% was recorded for
pregnant patients compared with 51% for nonpregnant patients treated during the same period.
Their statistics included not only patients treated during pregnancy but also those treated up to 6
months after delivery, and the postpartum group had the poorest survival statistics. Survival was

most closely related to stage, as expected, and persons diagnosed during the first trimester had a
better prognosis than those diagnosed during the third trimester.


Cervical Cancer in Pregnancy
Cervical cancer is one of the most common malignancies in pregnancy, with an estimated
incidence ranging from 1 in 1,200 to 1 in 2,200 pregnancies. Conversely, 1 of 34 women
diagnosed with cervical cancer is pregnant at the time of diagnosis. The most common complaint
of pregnant patients with cervical cancer is abnormal bleeding. However, confusion between the
symptoms of early cervical cancer and those of normal pregnancy frequently leads to a delay in
diagnosis. Pathologic confirmation of the presence of invasive cervical cancer should be
obtained by directed biopsy in the presence of a grossly visible lesion. Conization is indicated
only for those patients with apparent microinvasive disease on directed biopsy or for patients
with persistent cytologic evidence of invasive cancer in the absence of a colposcopically visible
lesion. Diagnostic conization should be considered only when a diagnosis of invasive cancer will
result in a modification of treatment recommendations, timing, or mode of delivery. From an
obstetric standpoint, the optimal time to perform conization is between 14 and 20 weeks
gestational age or after the time of fetal viability has been reached.
The same clinical staging system of cervical cancer is employed for both nonpregnant and
pregnant patients alike (Table 58.2). For pregnant patients with cervical cancer, MRI can provide
imaging while minimizing fetal exposure to ionizing radiation. Treatment recommendations are
individualized and are dependent on the stage of disease, gestational age at the time of diagnosis,
and the desires of the patient regarding continuation of the pregnancy. Patients with welldocumented stage IA1 disease (conization with negative surgical margins) may be managed with
vaginal delivery and reevaluation postpartum. If the patient has completed childbearing, a simple
extrafascial hysterectomy would be appropriate; otherwise, close clinical follow-up is required.
For patients with stage IA2 disease, a modified radical cesarean hysterectomy with pelvic lymph
node dissection is the preferred treatment. Patients with stage IB or IIA disease may be treated
with surgery in the form of radical hysterectomy and pelvic lymph node dissection, either in

conjunction with cesarean section or with the fetus in situ, depending on the gestational age.
Radiation therapy is the treatment of choice for patients with stage IIB to IVA disease or those
with stage IB and IIA disease who are not favorable candidates for radical hysterectomy.
Radiation therapy may be initiated with the fetus in situ for nonviable pregnancies, with
spontaneous abortion occurring 4 to 5 weeks after starting treatment. For more advanced
gestations, classic cesarean delivery is performed initially, with radiation therapy commencing 2
to 3 weeks following delivery. The issue of delaying treatment in order to reach a gestational age
consistent with fetal viability has been controversial. Although the data are limited and
retrospective in nature, it appears that a treatment delay of 6 to 12 weeks is not detrimental for
patients with localized (stage I) disease. Treatment delays are not recommended for patients with
more advanced disease.


Carcinoma of the Cervix during Pregnancy
Invasive carcinoma of the cervix in pregnancy is found more frequently in areas where routine
prenatal cytologic examination is done. Abnormal cervical cytology in pregnancy calls for
immediate colposcopic evaluation and any other diagnostic modalities necessary to exclude
invasive cancer (see section on preinvasive disease).
Invasive cervical cancer complicates approximately 0.05% of pregnancies. As is the case with
nonpregnant patients, the principal symptom is bleeding, but the diagnosis is frequently missed
because the bleeding is assumed to be related to the pregnancy rather than to cancer. The
possibility of cancer must be kept in mind. The diagnosis and management of invasive cervical
cancer during pregnancy presents the patient and the physician with many challenges. Pregnancy
does not appear to affect the prognosis for women with cervical cancer and the fetus is not
affected by the maternal disease, but may suffer morbidity from its treatment (eg, preterm
If the pregnancy is early and the disease is stage I to IIA, radical hysterectomy and therapeutic
lymphadenectomy can be performed with the fetus left in situ, unless the patient is unwilling to
terminate the pregnancy. Women at a gestational age closer to fetal viability or who are unwilling
to lose the baby may decide to continue the pregnancy after careful discussion regarding the
maternal risks. Delivery in patients with cervical dysplasia and carcinoma in situ may be via the
vaginal route. Patients with invasive cervical cancer should be delivered by cesarean section to
avoid potential cervical hemorrhage and dissemination of tumor cells during vaginal delivery. A
cesarean radical hysterectomy with therapeutic lymphadenectomy is the procedure of choice for
patients with stages IA2IIA disease as soon as adequate fetal maturity is established.

As in the nonpregnant patient, radiation with concomitant chemotherapy is used for the treatment
of more advanced disease. In the first trimester, irradiation may be carried out with the
expectation of spontaneous abortion. In the second trimester, interruption of the pregnancy by
hysterotomy prior to radiation therapy is preferred, although some physicians advocate
proceeding with immediate radiation treatment, again awaiting spontaneous evacuation of the
uterus. In selected cases with locally advanced disease in which the patient declines pregnancy
termination, consideration may be given to neoadjuvant chemotherapy in an effort to prevent
disease progression during the time needed to achieve fetal maturity. Delivery should be by
cesarean section. A lymphadenectomy can be performed at the same time. Postpartum the patient
should receive chemoradiation following guidelines established for the nonpregnant patient.