Treatment of Gynaecologic Malignancies During Pregnancy

Third international consensus meeting-based guidelines

Recent studies have shown that treatment of gynaecological malignancies during pregnancy is attainable, although oncological treatment needs to be individualised to ensure optimal maternal care and minimise potential effects to the foetus, while meeting the psychosocial needs of the family. It is a key message from the third international consensus meeting, sponsored by the European Society of Gynaecological Oncology, which aim was to disclose new evidence-based information and expert knowledge, to revise and strengthen the recommendations of the previous guidelines published in 2009 and 2014, to recommend appropriate techniques and to promote effective management of pregnant women with gynecological malignancies and their offspring. The latest guidelines are published on 21 August 2019 in the Annals of Oncology.

Prof. Frédéric Amant of the Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium and colleagues wrote that a lack of knowledge and the rarity of cancer in pregnancy spearheaded the creation of the International Network on Cancer, Infertility and Pregnancy (INCIP) that aims to contribute to the advancement of cancer management for pregnant women and facilitate large-scale studies. The INCIP has grown remarkably in the past years and now consists of 62 medical centres in 25 countries, which have registered over 2000 patients with a cancer diagnosis during pregnancy.

Since inception of the registration in 2005, a knowledge on how to manage gynaecological malignancies has increased tremendously. New insights and more experience have been gained since two previously published guidelines.

The rare combination of cancer and pregnancy is expected to rise, as already demonstrated by population-based studies. This will be most significant in countries where women tend to delay childbearing and where non-invasive prenatal testing that may reveal asymptomatic malignancies is easily available or reimbursed by insurance.

With an aim to provide comprehensive protocols and promote effective management of pregnant women with gynaecological malignancies, the INCIP members in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. The main conclusions from the experts’ panel are summarised below.

Treatment of gynaecological malignancies during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of healthcare providers. It allows further optimisation of maternal treatment, while considering foetal development and providing psychological support and long-term follow-up of the infants.

Non-ionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans.

In contrast to other cancer types, standard surgery for gynaecological malignancies often needs to be adapted according to cancer type and gestational age.

Chemotherapy is contraindicated in the first trimester of gestation to avoid interference with organogenesis; foetal benefit of treatment delay until the second trimester should be balanced against maternal risk. 

After 14 weeks of gestation, most standard regimens of chemotherapy can be administered. Administration of a number of anticancer drugs is feasible including taxanes, platinum agents, anthracyclines, etoposide and bleomycin. 

Dosing of chemotherapeutic drugs during pregnancy should be based on actual weight. 

Chemotherapy is not recommended beyond 35 weeks: it is important to give a 3-week window between the last cycle of chemotherapy and delivery to allow both maternal and foetal bone marrow to recover. 

Anti-VEGF and other antiangiogenic drugs are contraindicated during pregnancy. 

Until safety data are available, targeted therapies should be avoided during pregnancy. 

Metoclopramide, 5-HT3 antagonists, ranitidine, proton pump inhibitors, methylprednisolone, prednisolone or hydrocortisone can be used if necessary. 

Any radiation treatment to the pelvic region will deliver a significant dose to the foetus and should therefore be avoided if pregnancy is to be continued. Radiation doses in the therapeutic range, starting from the first fraction, will lead to foetal death. The probability for a new pregnancy after successful cancer treatment decreases with the delivered radiation dose to the uterine structures. If radiation therapy is indicated after termination of pregnancy, it is advised that the ovaries are marked with radiological visible clips to guide ovary-sparing radiation therapy to decrease the risk of premature menopause.

Caesarean section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers.

The placenta should be examined for metastatic disease. In the rare case that the placenta shows metastases, three monthly clinical follow-up of the child is recommended by a specialised cancer expert in a paediatric oncology centre. Metastasis to the foetus in gynaecological malignancies is exceptional.

Both the pregnancy/postpartum period and malignancy are risk factors for venous thromboembolism. Therefore, thromboprophylaxis with low-molecular-weight heparin should be considered, especially in postoperative setting or in the case of immobilisation.

Oncological treatment can be continued immediately after vaginal delivery, and 1 week after uncomplicated Caesarean section. It is also important to discuss postpartum contraception if fertility is maintained.

Breastfeeding is allowed if there is no ongoing chemotherapy, endocrine or targeted therapy, if the time since last administration is at least 3 weeks. More studies that focus on the long-term toxic effects of gynaecologic malignancy treatments are needed to provide a full understanding of their foetal impact. In particular, data on targeted therapies that became a standard of care in certain gynaecological malignancies is still limited.

The guidelines also provide recommendations for neonatal and paediatric care, as well as recommendations for psychosocial caregivers treating pregnant cancer patients and their families.

More studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted.

Participation in existing registries ( www.cancerinpregnancy.org) and the creation of national tumour boards with multidisciplinary teams of care providers is encouraged.

 

Reference

Amant F, Berveiller P, Boere IA, et al. Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting. Annals of Oncology; Published online 21 August 2019. pii: mdz228. doi: 10.1093/annonc/mdz228.