CANCER TREATMENT DURING PREGNANCY

Because cancer during pregnancy is a rare occurrence, with an incidence ranging from 0.02% to 0.10%, there is a scarcity of research to guide women and their physicians on treatment. Now, some experts have offered reassurance that it is possible to appropriately treat the mother without terminating the pregnancy.

Pregnancy should be preserved whenever possible with breast and gynecologic cancers, according to 2 separate review articles published in the February 11 issue of the Lancet. The most common malignancies diagnosed during pregnancy are gynecological (primarily uterine or cervical, and less frequently ovarian) and breast cancers; pregnancy does not have a deleterious effect on the prognosis of either.

Although prognosis and treatment success depends on the individual patient, it is possible to provide standard therapy to the mother while safeguarding the fetus.

Decisions about treatment for cancer in a pregnant woman can be difficult because of the conflict between the wellbeing of the mother and that of her unborn child, note Philippe Morice, MD, from the Institut Gustave Roussy, Villejuif, France, and colleagues in a comment accompanying the review papers.

They point out that the physician must define "when and how far to push back usual treatment limits to satisfy the patient's [ethical, legal, and/or personal beliefs]," but also must provide accurate information and consider the oncologic risks.

"The main goal is to offer pregnant patients the same optimum management (and therefore similar predicted survival) as nonpregnant patients," they write. Therefore, physicians must clearly define the real oncologic risk for each patient. Physicians need to stop thinking about cancer and pregnancy in general; instead, they need to focus on the particular cancer and its known characteristics.

Except for leukemia, true oncologic emergencies in pregnant women are rare, Dr. Morice and colleagues point out. This is fortunate because "time is required to deliberate and to draw up a personalized treatment plan that the patient will view as clear and balanced."

Treating cancer during pregnancy is still associated with unacceptable outcomes, such as the termination of pregnancies and the choice of an inadequate strategy for treatment of a tumor, they write.

"The treatment of every pregnant woman, and by extension every woman of childbearing age, should include a wider reflection on how to preserve the pregnancy or subsequent fertility, or both," Dr. Morice and colleagues explain. "Preservation of fertility in young women with cancer (an entirely new specialty, oncofertility) is every patient's right."

Pregnancy During Breast Cancer

In the review article on breast cancer during pregnancy, Frédéric Amant, MD, from the Multidisciplinary Breast Cancer Center, Leuven Cancer Institute, Katholieke Universiteit Leuven, Belgium, and colleagues note that a multidisciplinary focus and a cautious approach to radiotherapy are needed. A diagnostic strategy designed to reduce the burden of fetal radiation exposure needs to be established in a multidisciplinary setting.

Terminating the pregnancy does not improve the breast cancer prognosis, explained Dr. Amant. "We believe that fear of the toxic effects of chemotherapy should not be a reason for termination of pregnancy, and fear should not be a reason to delay maternal treatment or to induce prematurity," he told Medscape Medical News.

The therapeutic strategy should also be discussed within a multidisciplinary setting, and should adhere as closely as possible to standard protocols for nonpregnant women, say the authors, but fetal safety must also be considered.

Dr. Amant added that sometimes oncologists underestimate the long-term consequences of prematurity. "We believe children suffer more from prematurity than from antenatal exposure to chemotherapy," he said.

Until now, it was "easy to terminate pregnancy because the long-term effects were not known," said Dr. Amant. "With the current data, I believe it becomes unethical to terminate pregnancy when cancer is diagnosed."

A study recently published by Dr. Amant and colleagues showed that fetal exposure to chemotherapy was not associated with increased central nervous system, cardiac, or auditory morbidity. In addition, exposure did not appear to be associated with impairments to general health or growth, and cognitive development was age-adequate.

He added that if this trend is confirmed in more children with a longer follow-up, "I believe termination will be more difficult to defend."

In their review paper, Dr. Amant and colleagues explain that surgery, chemotherapy, and radiotherapy for breast cancer are possible during pregnancy, with the caveat that treatment should be tailored to the individual patient.

Generally, surgery can be conducted safely during any stage of pregnancy and most anesthetic agents seem to be safe for the fetus, they point out. The choice of surgery should follow the same guidelines as those for nonpregnant women, and radiation therapy after a breast-conservation procedure is rarely a concern; most women receive chemotherapy and delay radiotherapy until after delivery.

After the first trimester of pregnancy, chemotherapy can be either adjuvant or neoadjuvant, and the decision to use chemotherapy should follow the same guidelines as for nonpregnant women, the authors report. The goal should also be a term delivery (37 weeks or more), and premature birth should be avoided if possible.

Cervical and Ovarian Cancers During Pregnancy

In the review paper on gynecologic cancers, Dr. Morice and his colleagues from France and the United States focused on the 2 most common and complex gynecologic cancers — cervical and ovarian. As in breast cancer, a multidisciplinary discussion is essential for optimal disease management, note the authors. Physicians need to consider the possibility of saving the fetus and the effect of therapy on the woman's reproductive capacity.

Dr. Morice and colleagues point out that until the 1980s, cervical cancer diagnosed during the first 2 trimesters was managed by ending the pregnancy and radically treating the cervical neoplasm. The current trend is to try to preserve the pregnancy, especially in patients with early-stage disease with no nodal involvement.

The management of cervical cancer depends largely on 4 criteria: the extent of local spread, nodal status, pregnancy trimester, and histologic subtype. The authors explain that in early-stage cervical cancer, during the first and at the beginning of the second trimester, magnetic resonance imaging and laparoscopic lymphadenectomy can be used to help plan a conservative approach.

Among women with small tumors and without nodal spread, postponing treatment until fetal maturity and delivery can be discussed. In these cases, radical trachelectomy and neoadjuvant chemotherapy might be appropriate.

The treatment of patients with locally advanced disease is controversial — neoadjuvant chemotherapy with preservation of the pregnancy or chemotherapy and radiotherapy — and needs to be discussed on a case-by-case basis. Tumor size, radiologic findings, the term of pregnancy, and the patient's wishes must be taken into consideration, the authors note.

The management of ovarian cancer is dependent on histologic type, stage, and pregnancy trimester. In patients with peritoneal spread or high-risk early-stage disease, preservation of the pregnancy might be possible with neoadjuvant chemotherapy, according to Dr. Morice and colleagues.

Chemotherapy is generally necessary to achieve a cure in ovarian cancer, and the risk for a congenital malformation or miscarriage as a consequence is very high during the first trimester. In such cases, "consideration of a therapeutic abortion versus delayed treatment should be discussed with the patient," they write. However, treatment during subsequent trimesters can be given according to the usual standard chemotherapy guidelines for both germ-cell tumors and epithelial ovarian cancer; in most cases, there are generally no irreversible consequences for the fetus.

It is also usually not necessary to induce premature delivery if the cancer is controlled with chemotherapy.

"Clinical studies are needed, particularly for key issues in clinical management, such as an intentional delay in early-stage cervical cancer or radical trachelectomy and neoadjuvant chemotherapy, to establish the balance between the best chance of cure for the patient and preservation of a healthy fetus," Dr. Morice and colleagues emphasize.

Nefertiti duPont, MD, MPH, who was approached by Medscape Medical News for an independent comment, noted that this is "an excellent review of a difficult topic."

"When diagnosed early, gynecologic cancers in pregnancy can lead to good outcomes for the mother and infant," said Dr. duPont, who is assistant professor and director of the High Risk Ovarian Cancer Screening Clinic, Roswell Park Cancer Institute, Buffalo, New York. "The most important issues are close follow-up of the mother during her pregnancy and postpartum course, and long-term follow-up of the infant."

What is also critical is a multidisciplinary team to ensure that the mother and baby have the best possible outcomes, she explained.

Several areas in the review, however, could be strengthened, Dr. duPont noted. "Clinicians should provide psychosocial and emotional support to the mother during diagnosis and treatment," she said. "Also, most studies recommend postponing chemotherapy within 3 weeks of delivery to avoid neonatal myelosuppression."

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