Berek and Hacker's Gynecologic Oncology, 5th Edition

17

Cancer and Pregnancy

Amreen Husain

Maurice Druzin

 

The diagnosis of cancer during pregnancy is a serious medical and psychological challenge to the woman, her family, and her caregivers. Pregnancy is normally a happy time with great expectations for the future, and the diagnosis of a life-threatening illness may lead to inappropriate responses by the patient, her family, and the medical team. When faced with a diagnosis of cancer in pregnancy, the single most important question that the obstetrician must ask of the oncologist is: “What would the optimal therapy be for this patient with this diagnosis if she were not pregnant?” The answer will almost always be appropriate for the pregnant patient.

Cancer in pregnancy presents many challenges and requires management by a team which should include a gynecologic oncologist, a maternal-fetal medicine specialist, a medical oncologist, a radiation oncologist, and a neonatal pediatrician. The issues relate to the type of cancer with which the woman is diagnosed, the gestational age at which the diagnosis is made, the stage at which the cancer is diagnosed, the social and ethical attitudes of the woman with respect to pregnancy termination, and the ongoing management of the pregnancy.

Cancer complicates approximately 1 in 1,000 pregnancies. The most commonly diagnosed cancers in pregnancy are cancer of the breast and cervix, melanoma, and Hodgkin's disease(1). The diagnostic and therapeutic management of cancer in pregnancy needs to take several matters into consideration, including the risk of diagnostic procedures to the unborn fetus, the risks of therapeutic interventions to the ongoing pregnancy, and the social implications of child bearing and motherhood for the woman. Ideally, the cancer and the pregnancy must be managed without negatively affecting outcomes for the baby or the mother. This is not always possible, and appropriate counseling in these situations is essential.

Diagnosis

Overall, the outcomes of cancer in pregnancy are not worse than in the nonpregnant state. While it has been speculated that cancer outcomes in pregnancy are worse than in nonpregnant patients, this impression has not been supported by multiple studies over the last four decades, and suboptimal treatment of the cancer in pregnancy may be responsible for this erroneous assumption (2).

The most critical issue in the diagnosis and treatment of cancer in pregnancy is to avoid unnecessary delay. Delay may cause more harm than well-planned diagnostic and therapeutic interventions, which for the most part pose minimal risk to the unborn fetus after the first trimester. Many signs and symptoms of cancer can be misinterpreted as being due to the pregnancy, leading frequently to delayed evaluation. If a physical symptom is found in a pregnant woman that may indicate a malignancy, the best principle to follow is to investigate it in the same manner as for a non-pregnant woman.

Diagnostic Testing

With few exceptions, most diagnostic modalities are safe in pregnancy. Ultrasound has a long safety record during pregnancy, and most radiologic procedures will cause insignificant amounts of fetal radiation exposure when used judiciously and with appropriate shielding. It is inappropriate to delay necessary diagnostic procedures based on theoretical and unproven risks to the fetus. Magnetic resonance imaging is ideal for scanning the pelvis and abdomen during pregnancy, as it delivers no radiation. Diagnostic imaging in pregnancy must be used judiciously—the axiom of “do not perform a test unless you are going to use the information for expediting the care of the patient” is most relevant under these circumstances.

Effects of Cancer Therapy on the Fetus

The majority of cytotoxic agents can cross the placenta and reach the fetus and thus the concern regarding effects of chemotherapy on the unborn child. Chemotherapy during the first trimester has been shown to increase the risk of spontaneous abortions, major malformations, and fetal demise and thus should be avoided unless termination of pregnancy is planned. Second and third trimester exposure is associated primarily with intrauterine growth restriction and low birth weight as well as potentially preterm deliveries and neonatal myelosuppression (3,4,5).

Of the different types of chemotherapeutic agents, the antimetabolites are more likely to be teratogenic than alkylating agents or anthracyclines. Long-term studies of infants born to mothers treated with chemotherapy for hematologic malignancies in pregnancy have reported normal physical, neurological, and psychological development as well as no increased risk of childhood malignancies (3,4,5).

The use of radiotherapy in pregnancy has been reported much less frequently but with appropriate treatment planning and shielding of the fetus, tumors not involving the pelvis or abdomen which require radiation therapy can be treated, with good overall outcomes (6).

Management of the Ongoing Pregnancy

Gestational age of the pregnancy is a critical component of the information required to offer optimal therapy (Fig. 17.1). For example, in a patient diagnosed with cancer in the first or early second trimester, termination should be discussed with the patient and her family as a therapeutic option if the treatment would otherwise disrupt the pregnancy. If the decision is made to continue the pregnancy, careful counseling concerning the risks, benefits, and alternatives to diagnostic and therapeutic intervention must be thoroughly discussed with the patient.

Surgical removal of tumors is often possible with minimal risk of disrupting the pregnancy. Surgery during the early second trimester is ideal, but surgery at any gestational age is reasonable if it will maximize the chance of cure and long-term survival (7). Delivery of the fetus is often advocated but rarely necessary. Each case is unique and therapy must be carefully individualized.

If surgery is performed after 24 weeks, which is considered the lower limit of viability, careful attention must be paid to adequate fluid replacement and prevention of hypotension.Fetal monitoring is recommended, with emergency cesarean section being reserved for imminent fetal compromise.

Antenatal corticosteroid therapy for induction of fetal lung maturity should be considered in all cases after 24 weeks of gestation (8,9). The beneficial effects of steroids on fetal lung, brain, and bowel development allow the obstetric and oncologic teams to plan interventions and to have flexibility to perform an early delivery if necessary.

Fetal surveillance should be instituted after 28 weeks. This should include serial obstetrical ultrasonography to evaluate fetal growth and placental function, and a combination of nonstress testing, biophysical profile testing, and umbilical artery Doppler measurements.

Consideration for Delivery After 32 Weeks' Gestation

The method of delivery should be determined by obstetrical indications. The presence of a malignancy is not an indication for cesarean delivery per se. In a modern neonatal intensive care unit, the neonatal survival rate at 28 weeks' gestation following antenatal corticosteroid administration is well above 90%. In addition, long-term neurologic outcome is near normal in over 90% of survivors (10). These encouraging neonatal statistics afford the obstetric and oncologic teams the flexibility to institute optimal maternal therapy, while also allowing for a successful pregnancy outcome.

 

 

Figure 17.1 Management of a non-gynecologic cancer during the three trimesters of pregnancy.

Specific Cancers in Pregnancy

Cervical Intraepithelial Neoplasia and Invasive Carcinoma of the Cervix

Pregnancy represents an opportunity to screen women for a variety of conditions and often this represents the only occasion when some women will have cytologic screening for cervical cancer. The reported incidence of cervical cancer is 1.2 per 10,000 pregnancies (1).

Management of an Abnormal Pap Test in Pregnancy

Currently the recommendations for addressing abnormal Pap tests during pregnancy favor a conservative approach in the absence of frankly malignant cells. The ASCCP guidelines (11) generally recommend that women with an abnormal pap smear concurrently have HPV testing performed. An algorithm for the management of the abnormal Pap test in pregnancy is presented in Fig. 17.2.

Positive High-Risk HPV

In women with negative cervical cytology and a positive high-risk HPV test, a repeat of both tests is recommended at 12 months. For pregnant women, it is recommended that this be repeated at the 6-week postpartum visit (11).

ASC-US

In women with an ASC-US Pap smear but high-risk HPV negative test, the recommendation is also to repeat both at the 6-week postpartum visit (11). The chance of finding an invasive lesion following a minimally abnormal Pap smear antepartum or postpartum is less than 1% in women with an ASC-US Pap smear and a positive high-risk HPV test. The current guidelines recommend that for women older than 21 years of age, ASC-US and a positive HPV test may be managed by colposcopy at the time of diagnosis, or colposcopy may be deferred until the postpartum evaluation (11).

 

 

Figure 17.2 Management of abnormal Pap test in pregnancy as per ASCCP guidelines. (CIN = cervical intraepithelial lesion, HPV = human papilloma virus, LSIL = low-grade squamous intraepithelial lesion, HSIL = high-grade intraepithelial lesion, ASC-US = atypical squamous cells of undetermined significance. ASC-H = atypical squamous cells, cannot exclude high-grade, AGC = atypical glandular cells, AIS = adenocarcinoma in situ)

LSIL

Patients with LSIL on cervical cytology are extremely unlikely to have an invasive lesion and a study by Jain et al. found none of 287 patients had an invasive lesion on antepartum biopsy (12). Thus, the current ASCCP guidelines state that colposcopy is preferred for the nonadolescent pregnant woman with LSIL, but deferring this procedure until at least 6 weeks postpartum is an option provided there is no cytologic or macroscopic evidence of a more invasive process (11,12,13,14).

HSIL

Patients with HSIL on a Pap smear should undergo colposcopy (11). Because of the increased vascularity of the cervix during pregnancy, the colposcopic findings are exaggerated, and are more difficult to interpret. Therefore, those with an expertise in this area should perform colposcopy during pregnancy.

Women with HSIL on a Pap smear should be referred antepartum for expert colposcopic evaluation and they should undergo colposcopically directed biopsies of any suspicious findings. There is a risk of excessive bleeding from the cervix, but most studies have reported no significant adverse outcomes from colposcopically directed biopsies during pregnancy (13,14). The general recommendation is to defer colposcopy until the second trimester, although the vascularity of the cervix is significantly increased after the first trimester. In all cases, endocervical curettage should be avoided, although this is primarily because there have been no trials to evaluate the risk (13,14).

Atypical Glandular Cells

Atypical glandular cells (AGC) on a Pap smear should be thoroughly evaluated at any time during pregnancy and the pregnant woman with atypical glandular cells or adenocarcinomain situ on a Pap smear should undergo colposcopically directed biopsies and if indicated, cervical conization or loop electrosurgical excision procedure (LEEP) (14).

 

Treatment of CIN 2-3

The risk of progression of cervical intraepithelial neoplasia (CIN) 2-3 to microinvasive or frankly invasive carcinoma is minimal, and the rate of spontaneous postpartum regression of CIN 2-3 is relatively high, so the treatment of CIN during pregnancy should be observation unless there is a strong suspicion of microinvasive or invasive disease (15). If indicated, a LEEP procedure can be performed in pregnancy but significant bleeding may occur and the practitioner should be prepared to deal with this potential. LEEP should primarily be reserved for patients in the early stages of pregnancy in whom the presence of invasive disease is strongly suspected (15).

All patients with abnormal Pap smears or cervical dysplasia during pregnancy should be reevaluated 6 to 8 weeks postpartum with repeat Pap testing and colposcopic evaluation. Patients with cervical intraepithelial neoplasia in the absence of other contraindications can safely undergo vaginal delivery. Furthermore, an increased rate of regression after vaginal delivery (as opposed to cesarean section) for LSIL and HSIL has been reported, which may obviate the need for an excisional procedure postpartum (15,16).

Invasive Cervical Cancer in Pregnancy

Worldwide, invasive cervical cancer is the most common cancer of the female reproductive tract with approximately half a million annual cases and 250,000 deaths (17). Most of these cases are seen in developing countries in reproductive-age women, which explains the high rate of cervical cancer in pregnancy. Though relatively uncommon in the United States, this is a significant international health problem.

Cervical cancer is one of the most common cancers diagnosed during pregnancy. The diagnosis and treatment of cervical cancer during pregnancy should be managed by a multidisciplinary team, and treatment will depend on the stage and the gestational age at diagnosis, and the patient's desires and beliefs regarding continuation versus termination of the pregnancy (18).

Management

Stages IA1/IA2

Early stage cervical cancer can often be managed conservatively. If stage IA1 disease is diagnosed on the basis of a cone biopsy with negative margins, it is reasonable to follow the pregnancy until term and anticipate vaginal delivery.

In patients with stage IA2 disease identified before 20 to 24 weeks' gestation, pelvic lymphadenectomy should be performed. If the nodes are positive, standard therapy should be recommended. If the nodes are negative, a cone biopsy with clear margins should be sufficient treatment for the primary lesion. After 24 weeks, it is reasonable to await lung maturity, deliver the baby by caesarian section, and treat the cancer postpartum.

The complications associated with cervical conization in pregnancy are significant. Cervical conization has been associated with significant hemorrhage in 5% to 15% of patients and miscarriage rates as high as 25% (19,20). Delaying treatment of an occult lesion probably has no impact on overall survival, as the likelihood of significant progression during a pregnancy is small (21). Most earlier reports pertained to squamous cell carcinomas, and management of adenocarcinomas of the cervix remains somewhat controversial, but several recent reports have described conservative management of adenocarcinoma in situ and early invasive adenocarcinoma in pregnancy (22,23).

Stages IB/IIA

In patients with frankly invasive carcinomas, the gestational age at diagnosis impacts more significantly on the treatment recommendations, as well as the patient's desire to continue the pregnancy (24,25).

In the first and early second trimester, treatment options for patients with Stage IB or Stage IIA disease include radical hysterectomy with the fetus in situ versus standard chemoradiation therapy. The survival rates for patients having stage IB or IIA cervical carcinoma treated in early pregnancy are similar to nonpregnant patients (24,25).

If the patient selects to undergo conservative management, or if the diagnosis is not made until after 24 weeks, she should be followed until fetal lung maturity has been achieved, then delivered by classical cesarean section followed immediately by a radical hysterectomy and pelvic lymphadenectomy (24,25,26). Delivery by classical cesarean section is recommended and may have better outcomes as seen in the report by Sood et al. (26) who reported a 14% recurrence rate (1 in 7) among patients delivered by cesarean section versus a 56% recurrence (10 in 17) among those patients delivered vaginally. Others though have found no benefit to cesarean versus vaginal delivery (27). The later has a significantly higher risk of hemorrhage, infection, and potential for episiotomy site metastasis.

P.659

 

 

Figure 17.3 Management of cervical cancer in pregnancy.

Advanced Disease

Patients with stage IB2 to IVA disease, should be offered pelvic radiation including external beam with concurrent chemotherapy if diagnosed in the first 20 weeks of pregnancy (28).An algorithm for the treatment of advanced stage cervical cancer is presented in Fig. 17.3. Treatment should be given with the fetus in situ. After several treatments of external beam therapy, a spontaneous termination of pregnancy should occur. However, for patients in whom the psychological impact of this approach would be potentially devastating, it is reasonable to offer termination of pregnancy by hysterotomy or by in utero intracardiac injection (28) which will then result in spontaneous expulsion of the fetus or potentially require uterine evacuation. Radiation can be started prior to evacuation of the fetus particularly if it is needed to control bleeding from a bulky tumor.

Management of advanced cervical cancer diagnosed after 20 to 24 weeks will usually be conservative. A delay of treatment for 6 to 8 weeks will significantly improve fetal outcome, without impacting negatively on maternal outcome (29,30). Therefore, if there is no significant urgency because of heavy bleeding or ureteric obstruction, it is reasonable to observe until acceptable fetal maturity has been reached, then undertake classical cesarean section. Chemoradiation should be commenced as soon as possible post-cesarean section, usually within 2-3 weeks.

 

Neoadjuvant chemotherapy in patients with locally advanced cervical cancer who strongly desire a significant delay in treatment has been reported. This approach has the potential to allow the fetus to mature before instituting delivery and definitive radiotherapy, but the reports are anecdotal and data regarding safety and outcome are limited. Appropriate counseling and multidisciplinary management in these cases is essential. Maran et al. reported a case of a 26-year-old diagnosed with Stage IIB disease at 14 weeks' gestation who delivered a healthy infant at term and declined additional cancer treatment after being treated with cisplatin 50 mg/m2 on days 2 and 3 and bleomycin 30 mg on day 1 for three cycles every 3 weeks (29). Tewari et al. (30) reported on two cases treated with cisplatin and vincristine with successful regression of tumor allowing completion of pregnancy followed by radical hysterectomy. One patient with Stage IB2 (7 cm lesion) was without evidence of disease at 2 years but the other (stage IIA, 4.5 cm lesion) recurred after 5 months. An additional paper reported one patient treated with cisplatin and vincristine for four cycles between 23 to 33 weeks' gestation with good long-term outcome (31). The literature has three additional case reports (32,33,34). This approach to cervical cancer in pregnancy must be considered experimental and used only in very exceptional circumstances where the woman has been extensively counseled regarding the lack of adequate supportive data.

Adnexal Masses and Ovarian Cancer in Pregnancy

One of the most frequent reasons for surgical intervention in pregnancy is the diagnosis of an adnexal mass, which occurs with an incidence of between 0.2% and 2% of pregnancies(35). Approximately 90% of adnexal masses diagnosed in the first trimester of pregnancy are corpus luteum cysts of pregnancy, and will resolve spontaneously. Therefore, surgical intervention is not recommended until early in the second trimester. The majority of lesions that persist are benign, and include teratomas and other benign ovarian neoplasms. Malignant and borderline ovarian tumors are rare during pregnancy (35).

The decision to operate for an adnexal mass must take into account the risks and benefits of the surgical intervention. Although the risk of malignancy is very low, the risk of torsion may be anywhere from 6% to 20%, and there are also risks of obstructed labor or an abnormal fetal lie.

The overall risk of surgical intervention during pregnancy is thought to be low and in a review of about 12,000 cases of surgery during pregnancy, Cohen-Kerem and colleagues concluded that surgery does not increase the risk for miscarriage or congenital anomalies. Premature deliveries occurred in 3.5% of cases, mainly after abdominal surgery and peritonitis in the third trimester (36).

Laparoscopic surgery has also been reported during pregnancy and has been found to be safe. Although it does offer advantages, only limited data are available and it should only be performed by a very experienced gynecologist (37,38). The management of an adnexal mass in pregnancy should be a collaboration between a gynecologic surgeon and a maternal-fetal medicine specialist, giving careful consideration to the size and ultrasonic features of the mass, and the gestational age at diagnosis.

Leiserowitz et al. (39) reported a population-based study of 4,846,505 obstetrical patients using the California hospital discharge records from 1991 to 1999. There were 9,375 women (0.2%) who had a hospital diagnosis of an ovarian mass associated with pregnancy. The California Cancer Registry database identified 87 ovarian cancers (0.93% of adnexal masses) and 115 ovarian low malignant potential tumors (1.2% of adnexal masses) in the same cohort. Thirtyfour of the 87 ovarian cancers (39%) were germ cell tumors. Malignant ovarian tumors had an adverse affect on maternal morbidity including increased need for cesarean section, hysterectomy, blood transfusion, and extended hospitalization. There did not appear to be any adverse affect on neonatal outcomes.

Schmeler et al. (40) reviewed the records of pregnant patients diagnosed with adnexal masses 5 cm or greater in diameter and compared patients who had surgical intervention with those having observation. At the Women's & Infant's Hospital of Rhode Island, Brown University Medical School, Providence, RI, between 1990 and 2003, adnexal masses 5 cm or larger were diagnosed in 63 of 127,000 pregnant women for a rate of 0.05%. Antepartum surgery was performed in 17 patients (29%), the majority for ultrasonic findings suggestive of malignancy.

 

In four patients, the surgery was performed because of an ovarian torsion. The remaining patients were observed and surgery was performed in the postpartum period or at the time of cesarean delivery when a cesarean was performed for obstetric indications. They found four patients (6.8%) with an ovarian cancer and one patient (1.7%) with a tumor of low malignant potential. The ultrasonic findings in all five patients prompted surgical intervention. Thus no case of malignancy was missed. They recommend observation with postpartum surgery provided the ultrasonic findings were not highly suspicious for malignancy.

Yen et al. (41) followed 174 pregnant patients presenting with adnexal tumors ≥4 cm diameter. Fourteen percent of patients experienced torsion, and these occurred primarily in adnexal masses between 6 and 8 cm. Sixty percent of torsions occurred between 10 and 17 weeks of gestation and only 6% occurred after 20 weeks. The incidence of malignancy was 3.4% with the greatest risk being in tumors larger than 10 cm at initial diagnosis. Tumor growth greater than 3.5 cm per week was also associated with a significantly higher risk of malignancy. The authors recommended surgical intervention for tumors between 6 and 8 cm if diagnosed before the 20th week of gestation and for any adnexal mass with sonographic findings suspicious for malignancy or undergoing significant growth rate during ongoing observation.

The incidence of ovarian malignancy is very low in pregnancy; however, the potential for missing a malignant tumor of the ovary certainly exists in these reproductive-age women, and a suspicious ovarian mass should be removed surgically in the second trimester of pregnancy. Surgical outcomes in a well-controlled setting are excellent during pregnancy (39).

The majority of cancers are early stage, and chemotherapy can usually be withheld until after delivery for stage I epithelial tumors (42,43). Germ cell tumors are uncommon, but if there is an indication for chemotherapy, then treatment should be undertaken as soon after expedited delivery, as possible or during the second or third trimester. Most of these cancers have a good prognosis for both the woman and the infant (42,43).

Breast Cancer in Pregnancy

Breast cancer is the most commonly diagnosed invasive malignancy during pregnancy and the postpartum period. The incidence has been reported to be 1 in 10,000 to 1 in 3,000 and it is thought that with the trend toward delayed child-bearing, the incidence of breast cancer diagnosed during pregnancy will increase further (44). Overall 3% of women diagnosed with breast cancer will be lactating or pregnant at the time of diagnosis (44). The diagnosis may be delayed due to physiologic changes which may obscure a breast mass, or lead to a mass being attributed to the pregnancy or lactation.

Frequently the stage of breast cancer diagnosis during pregnancy is higher than in nonpregnant patients, either due to delayed diagnosis or to a promotional effect of gestational hormones on breast tumors, causing an intrinsic biological aggressiveness. When controlled for stage, pregnancy per se does not confer a worse prognosis (45,46).

Any woman who presents with a breast abnormality should have it completely investigated, regardless of pregnancy or lactation. Diagnostic mammography can be performed with minimal risk to the fetus with the use of abdominal shielding, but mammography may be of limited value due to the denseness of breast tissue during pregnancy and lactation. Ultrasonography can be an accurate method of identifying cystic and solid lesions, and can be used to guide fine needle aspiration (47).

Once the initial diagnosis and metastatic workup has been accomplished, treatment should be instituted immediately. Pregnancy termination does not need to be routinely recommended, but some women may choose to terminate the pregnancy in order to expedite the treatment options (48).

The treatment strategies for pregnant women should be the same as for nonpregnant women with breast cancer. Initial surgical resection followed by postoperative adjuvant therapy is the standard of care and should be undertaken with minimal delay. If the diagnosis is made in the first trimester any chemotherapy should be delayed until the second or third trimester. If necessary, therapeutic radiation treatment may be instituted during pregnancy, with appropriate shielding to reduce fetal exposure. The level of ionizing radiation to the fetus that is absolutely safe is not known (48).

 

Any patient diagnosed with breast cancer during pregnancy should be managed by a multidisciplinary team, and the patient should be counseled regarding possible pregnancy outcomes related to the diagnostic and treatment methodologies employed (48).

Malignant Melanoma in Pregnancy

The incidence of cutaneous malignant melanoma has been increasing by 3% to 5% per year, with an increased incidence in women (49). The skin changes that occur in pregnancy can make diagnosis more difficult but any suspicious lesion should be fully evaluated and treated appropriately. The effects of pregnancy hormones on malignant melanoma remain controversial, though recent studies have shown no significant difference in survival between pregnant and nonpregnant women with melanoma, given similar prognostic factors, including tumor thickness (49). With early diagnosis and treatment excellent outcomes can be expected without any negative impact of the pregnancy on the disease.

O'Meara et al. from California reported the largest population based study of pregnant women with malignant melanoma (50). They recruited patients from 1991 to 1999, and compared women who had pregnancy associated melanoma with age matched controls. In their database, the incidence of pregnancy associated melanoma in California was 8.5 per 100,000 pregnant women. This was compared to the national SEER statistics from 1975 to 2000 which showed that the incidence of melanoma in women aged 20 to 45 years ranged from 6 to 21.2 per 100,000. They reported no difference in stage, tumor thickness, lymph node involvement, or survival between the two groups. The study was somewhat limited by the fact that the women who terminated their pregnancy prior to 20 weeks may not have been included, and there were very small numbers of women with advanced melanoma in the study group. The most important prognostic factor was tumor thickness, which is the same for nonpregnant women. A large Swedish study also found no differences in outcome for pregnant versus nonpregnant women with melanoma (51).

The potential for metastasis to the placenta in pregnant women with melanoma warrants careful histologic evaluation by pathologists. With placental involvement, fetal risk of melanoma metastasis is approximately 22%. Neonates delivered with concomitant placental involvement should be considered at high risk, must be followed with vigilance (52).

Lymphoma and Leukemia in Pregnancy

The median age of presentation of Hodgkin's disease is 30 years and given that this is the peak reproductive age, the diagnosis of Hodgkin's disease in pregnancy occurs in one in 6,000 pregnancies. Diagnosis by lymph node biopsy can be performed safely in the pregnant patient and any suspicious adenopathy should be assessed regardless of the gestational status.

Hodgkin's lymphoma and non-Hodgkin's lymphoma should be treated as in nonpregnant patients. Second and third trimester exposure to chemotherapeutic agents is not associated with fetal malformations, but there is an increase in the risk of fetal or neonatal death, intrauterine growth restriction (IUGR), preterm delivery, and low birth weight.

If the diagnosis of lymphoma is made during the first trimester, termination of pregnancy is recommended as there is a 10% to 20% incidence of congenital anomalies with first trimester exposure to chemotherapeutic agents. In cases of low grade or indolent lymphoma or if a patient desires to maintain the pregnancy, treatment should be instituted in the second trimester (53).

Women treated for lymphoma during pregnancy have the same recurrence rate and survival as their nonpregnant counterparts (53).

Leukemia in pregnancy is extremely rare but presents a very difficult challenge for both the patient and the treating physicians. Treatment for leukemia should be started as soon as possible after the diagnosis has been made regardless of the gestational age. In early pregnancy, termination is considered to be the best course of action, given the teratogencity of antineoplastic agents and the potential for maternal complications during periods of extreme pancytopenia and immunosuppression (54).

 

Summary

The diagnosis of a malignant neoplasm in pregnancy is devastating, but the oncologist and obstetrician must be able to appropriately determine the best treatment options, and counsel the patient regarding the potential outcome for the pregnancy, and the likely prognosis for these various treatment options (55). Termination of pregnancy is unlikely to improve the maternal outcome, except for patients with invasive cervical cancer diagnosed in the first or early second trimester. Oncologic treatment modalities including surgery, chemotherapy, and radiation therapy (except to the pelvis or abdomen) can safely be given after the first trimester.

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Updated - 2008 FIGO Staging Tables

Addendum: The following tables contain the updated 2008 FIGO staging for cancer of the uterine cervix, endometrium, and vulva, and new staging for uterine sarcomas. The FIGO staging for gestational trophoblastic neoplasia and for cancers of the ovary, fallopian tube, and vagina remains unchanged.

Table 9.1A Carcinoma of the Cervix Uteri (2008)

Stage I

The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded)

 

IA

 

Invasive carcinoma which can be diagnosed only by microscopy, with deepest invasion ≤5 mm and largest extension ≤7 mm

 

 

IA1

Measured stromal invasion of ≤3.0 mm in depth and extension of ≤7.0 mm

 

 

IA2

Measured stromal invasion of >3.0 mm and not >5.0 mm with an extension of not >7.0 mm

 

IB

 

Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA*

 

 

IB1

Clinically visible lesion ≤4.0 cm in greatest dimension

 

 

IB2

Clinically visible lesion >4.0 cm in greatest dimension

Stage II

Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or to the lower third of the vagina

 

IIA

 

Without parametrial invasion

 

 

IIA1

Clinically visible lesion ≤4.0 cm in greatest dimension

 

 

IIA2

Clinically visible lesion >4 cm in greatest dimension

 

IIB

 

With obvious parametrial invasion

Stage III

The tumor extends to the pelvic wall and/or involves lower third of the vagina and/or causes hydronephrosis or non-functioning kidney**

 

IIIA

 

Tumor involves lower third of the vagina, with no extension to the pelvic wall

 

IIIB

 

Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney

Stage IV

The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to Stage IV

 

IVA

 

Spread of the growth to adjacent organs

 

IVB

 

Spread to distant organs

FIGO Committee on Gynecologic Oncology. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynecol Obst 2009;105:103-104.

All macroscopically visible lesions—even with superficial invasion—are allotted to stage IB carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5.00 mm and a horizontal extension of not >7.00 mm. Depth of invasion should not be >5.00 mm taken from the base of the epithelium of the original tissue—squamous or glandular. The depth of invasion should always be reported in mm, even in those cases with “early (minimal) stromal invasion” (∽1 mm). The involvement of vascular/lymphatic spaces should not change the stage allotment.

** On rectal examination, there is no cancer-free space between the tumor and the pelvic wall. All cases with hydronephrosis or non-functioning kidney are included, unless they are known to be due to another cause.

 

Table 10.6A Carcinoma of the Endometrium (2008)

Stage I*

Tumor confined to the corpus uteri

 

IA*

 

No or less than half myometrial invasion

 

IB*

 

Invasion equal to or more than half of the myometrium

Stage II*

Tumor invades cervical stroma, but does not extend beyond the uterus**

Stage III*

Local and/or regional spread of the tumor

 

IIIA*

 

Tumor invades the serosa of the corpus uteri and/or adnexae#

 

IIIB*

 

Vaginal and/or parametrial involvement#

 

IIIC*

 

Metastases to pelvic and/or para-aortic lymph nodes#

 

 

IIIC1*

Positive pelvic nodes

 

 

IIIC2*

Positive para-aortic lymph nodes with or without positive pelvic lymph nodes

Stage IV*

Tumor invades bladder and/or bowel mucosa, and/or distant metastases

 

IVA*

 

Tumor invasion of bladder and/or bowel mucosa

 

IVB*

 

Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes

FIGO Committee on Gynecologic Oncology. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynecol Obst 2009;105:103-104.

Either G1, G2, or G3.

** Endocervical glandular involvement only should be considered as Stage I and no longer as Stage II.

Positive cytology has to be reported separately without changing the stage.

 

Table 10.26 Staging for Uterine Sarcomas (Leiomyosarcomas, Endometrial Stromal Sarcomas, Adenosarcomas, and Carcinosarcomas) (2008)

(1) Leiomyosarcomas

Stage

Definition

Stage I

Tumor limited to uterus

 

IA

<5 cm

 

IB

>5 cm

Stage II

Tumor extends to the pelvis

 

IIA

Adnexal involvement

 

IIB

Tumor extends to extrauterine pelvic tissue

 

Stage III

Tumor invades abdominal tissues (not just protruding into the abdomen).

 

IIIA

One site

 

IIIB

> one site

 

IIIC

Metastasis to pelvic and/or para-aortic lymph nodes

Stage IV

 

 

IVA

Tumor invades bladder and/or rectum

 

IVB

Distant metastasis

(2) Endometrial stromal sarcomas (ESS) and adenosarcomas*

Stage

Definition

Stage I

Tumor limited to uterus

 

IA

Tumor limited to endometrium/endocervix with no myometrial invasion

 

IB

Less than or equal to half myometrial invasion

 

IC

More than half myometrial invasion

Stage II

Tumor extends to the pelvis

 

IIA

Adnexal involvement

 

IIB

Tumor extends to extrauterine pelvic tissue

Stage III

Tumor invades abdominal tissues (not just protruding into the abdomen).

 

IIIA

One site

 

IIIB

> one site

 

IIIC

Metastasis to pelvic and/or para-aortic lymph nodes

Stage IV

 

 

IVA

Tumor invades bladder and/or rectum

 

IVB

Distant metastasis

(3) Carcinosarcomas

Carcinosarcomas should be staged as carcinomas of the endometrium.

FIGO Committee on Gynecologic Oncology. FIGO staging for uterine sarcomas. Int J Gynecol Obst 2009;104:179.

Note: Simultaneous tumors of the uterine corpus and ovary/pelvis in association with ovarian/pelvic endometriosis should be classified as independent primary tumors.

 

Table 13.7A Carcinoma of the Vulva (2008)

Stage I

Tumor confined to the vulva

 

IA

Lesions ≤2 cm in size, confined to the vulva or perineum and with stromal invasion ≤1.0 mm*, no nodal metastasis

 

IB

Lesions >2 cm in size or with stromal invasion >1.0 mm*, confined to the vulva or perineum, with negative nodes

Stage II

Tumor of any size with extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with negative nodes

Stage III

Tumor of any size with or without extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with positive inguino-femoral lymph nodes

 

IIIA

(i) With 1 lymph node metastasis (≥5 mm), or (ii) 1-2 lymph node metastasis(es) (<5 mm)

 

IIIB

(i) With 2 or more lymph node metastases (≥5 mm), or (ii) 3 or more lymph node metastases (<5 mm)

 

IIIC

With positive nodes with extracapsular spread

Stage IV

Tumor invades other regional (2/3 upper urethra, 2/3 upper vagina), or distant structures

 

IVA

Tumor invades any of the following: (i) upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to pelvic bone, or (ii) fixed or ulcerated inguino-femoral lymph nodes

 

IVB

Any distant metastasis including pelvic lymph nodes

FIGO Committee on Gynecologic Oncology. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynecol Obst 2009;105:103-104.

The depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion.