Cancer & Pregnancy• Cancer and fertility• Coexistence of cancer and pregnancy (the mother with a malignant condition)
Many questions• Ethical issues in best management of the mother and fetus• Effect of cancer on pregnancy – Effect of the tumor – Effect of management Effect on the outcome of pregnancy, special care, mode of delivery, and fertitliy• Effect of pregnancy on cancer – Effect on biology – Effect on management • Diagnosis : manifestations and diagnostic methods • treatment
Volume 341(2) 8 July 1999 pp 120-121 Cancer during Pregnancy [Editorials] Resnik, Robert.University of California, San Diego, School of Medicine; La Jolla, CA 92093-0621
• Cancer is rare during pregnancy, occurring in only about 1 per 1000 live births.• More than half the cases are tumors of the uterine cervix, breast, or thyroid,• which can metastasize to the placenta but not the fetus
• The fact that most maternal tumors do not metastasize to the fetus emphasizes an additional role of the placenta in most circumstances - that of an effective barrier between mother and fetus.• However, the involvement of the placenta, and sporadically the fetus, by hematologic tumors and melanoma indicates that the placental barrier is imperfect.
• concurrence of pregnancy and cancer does raise complex therapeutic and ethical dilemmas, because the most appropriate and timely treatment for the mother may not be in the best interest of the fetus.
• Extraabdominal surgery and anesthesia during pregnancy rarely carry any risks to the fetus, and intraabdominal surgery may be safely carried out in the second trimester.
• However, fetal cells divide and differentiate rapidly during the first trimester, and• radiation and chemotherapy carry well- recognized risks to the fetus, including the risk of abortion, congenital abnormalities, or preterm birth.• As a result, physicians may be reluctant to treat the mother aggressively at the time of initial diagnosis. Instead, in many cases they defer treatment for several weeks or months, until the fetal lungs have matured.• This delay, however, may substantially reduce the mothers chance of surviving the disease.
• It is impossible to establish a threshold dose of ionizing radiation below which such treatment is safe for the fetus,• inasmuch as exposure during the first trimester to a dose as low as 10 cGy appears to increase the risk of fetal abnormalities and exposure to 3 to 5 cGy increases the risk of childhood cancers. The risk is negligible if exposure to the fetus is less than 1 cGy.• The dose of radiation, the gestational age of the fetus, and the practicability of shielding the fetus from radiation must be balanced against potential benefits to the mother
• When aggressive chemotherapy is administered to the mother during the first trimester, most fetuses develop normally. Nevertheless, drugs that preferentially interfere with rapidly growing tissues, such as methotrexate, can harm the fetus. Use of antagonists of folate, purine, or pyrimidine synthesis during organogenesis results in congenital malformations in 10 to 25 percent of fetuses, although this Figure is much lower if the mother receives only single-agent therapy.• Treatment after the first trimester, when structural development is largely complete, is reasonably safe in many diseases and more appropriate than postponement of treatment for several weeks or months, until a mature infant can be delivered.• Chemotherapy after the first trimester has been associated with slight increases in the incidence of preterm birth and fetal growth restriction and, when administered shortly before delivery, with transient neonatal myelosuppression. Nevertheless, the long-term outcomes of the children of women who received chemotherapy during the second or third trimester are generally good.
The Oncologist® 2002;7:279-287 Coexistence of Pregnancy and Malignancy NICHOLAS A. PAVLIDISDepartment of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece
gold standardsA. try to benefit the mother’s life;B. try to treat curable malignant disease of pregnant women;C. try to protect the fetus and newborn from harmful effects of cancer treatment,D. try to retain the mother’s reproductive system intact for future gestations.
SAFETY OF DIAGNOSTIC WORK-UP• Staging Radiodiagnostic Procedures – The radiation effect on fetal life seems to be dose dependent (Table 3). – the adverse effects of radiation are directly related to the stage of gestation: the earlier the stage, the more detrimental the expected effects
• staging imaging tests should be limited to those associated with the lowest exposure to ionizing radiation. Abdominal plain films, isotope scans, and computerized tomography should be avoided. In contrast, chest x-ray and abdominal ultrasound are indicated as staging procedures.• In certain cases, i.e., brain tumors or pheochromocytomas, magnetic resonance imaging is recommended since it has the benefit of avoiding ionizing radiation to the fetus.
CANCER January 15, 2004 / Volume 100 / Number 2
Ovarian cancer is the second most frequent gynaecological cancer complicating pregnancy
• Although the overall incidence of ovarian cancer is very low, the routine use of ultrasound in pregnancy has led to more frequent findings of adnexal masses, making diagnosis and management increasingly challenging
• The estimated incidence of ovarian tumours is approximately one in 1000 pregnancies. Of those tumours approximately 3–6% are malignant
presentation• A significant number of pregnant women are asymptomatic and are found to have an adnexal mass on physical examination, during ultrasound or at the time of Caesarean section.• Ovarian masses, however, may also cause various complications such as ovarian torsion, haemorrhage and rupture of cysts, sometimes requiring emergency laparotomy.
• Adnexal masses during pregnancy are treated according to – the patient’s symptoms, and – the degree of suspicion regarding malignancy derived from the tumour’s characteristics,including imaging – and the gestational age
• Simple, unilateral masses less than 5 cm in diameterdetected in the first trimester are functional in most cases and represent follicular or corpus luteum cysts.• More than 90% of these functional cysts involute and are undetectable by the 14th week of gestation.
• if adnexal tumours are – greater than 5 cm in diameter, – persist into the second trimester, – are found in both adnexa – and/or have ultrasonographic features including solid components, papillary projections, septations or multicystic appearance,then further investigation is warranted.
• Magnetic resonance imaging, as an imaging modality without ionising radiation exposure, may provide additional information on a pelvic mass detected during ultrasound. Small studies suggested that MRI aids in the differential diagnosis of ovarian masses thus permitting expectant management in a subset of women.
• Most of the common tumour markers for ovarian neoplasms, such as CA125, α- fetoprotein, human chorion gonadotropin, lactate dehydrogenase and inhibin are elevated and fluctuate with gestational age. They are therefore of limited value during pregnancy.
• If surgical intervention is indicated and none of the above mentioned complications warrant emergency surgery,• laparotomy is commonly delayed until 16–18 weeks’ gestation.• At this time hormonal dependence of the pregnancy from the corpus luteum and the risk of spontaneous abortionis minimised.
• Surgical exploration using a midline incision is recommended to limit uterine manipulation and to enable adequate staging and debulking.• Depending upon the appearance of the adnexal mass either a simple cystectomy or oophorectomy is carried out after peritoneal washings have been collected.• A frozen section diagnosis must be made to guide further decisions
• Consistent with the young age of these patients, germ cell tumours and epithelial borderline malignancies are common ovarian malignancies in pregnancy
• In the germ cell category, dysgerminomas are most frequently encountered in pregnancy.• For most patients with ovarian germ cell tumours, unilateral salpingo-oophorectomy with preservation of the contralateral ovary and the uterus followed by surgical staging is adequate.• It is therefore possible to continue the pregnancy.• Staging should include omental and peritoneal biopsies and pelvic and paraaortic lymph node sampling. Routine biopsy of the contralateral ovary is only warranted if the ovary appears to be affected by tumour
• Similar to germ cell tumours, early stage low malignant potential epithelial and sex cord-stromal tumours can be managed by unilateral adnexectomy and staging and the pregnancy continued.
• Invasive epithelial ovarian cancers associated with pregnancy are staged in the same manner as in non-pregnant patients.• The extent of surgical debulking, however, needs to be adjusted according to the patient’s wishes, the stage of disease, and the fetal age and viability.• Removal of the gravid uterus, however, is rarely indicated.
• Cumulative published works suggests that laparoscopic surgery for benign adnexal masses is reasonably safe in pregnancy and has similar maternal and fetal outcomes as laparotomy
• Possible risks of laparoscopy in pregnancy, however, include – injury to the pregnant uterus, – decreased uterine blood flow secondary to increase in intra-abdominal pressure and the – carbon dioxide absorption by the fetus. – Potential drawbacks are also technical difficulties of laparoscopic surgery as a result of the enlarged pregnant uterus.
• The main obstacle for laparoscopic surgery is the preoperative difficulty of distinguishing accurately between benign and malignant lesions.• Opening of malignant cysts has been shown to be a significant adverse prognostic factor and should be avoided whenever possible• it is also impossible to perform adequate staging because of limited exposure and the inability to palpate unvisualised areas
Adjuvant therapy• With the exception of the low-risk grade I– II stage IA or IB malignancies, most germ cell tumours and invasive epithelial carcinomas require adjuvant chemotherapy
• Given the poor prognosis of ovarian malignancies treatment cannotbe delayed in affected patients.• The decision to start cytotoxic therapy in a pregnant patient remains a dilemma.• The main concern is the effect of the drugs on the developing fetus and the long-term sequelae in offspring born after exposure in uterus.• The effect of pregnancy on the pharmacology of the chemotherapeutic drugs is also an important issue.
• The estimated risk of congenital malformations with single agent chemotherapy during the first trimester is over 10% and increases when combinations of cytotoxic agents are used.• After the first trimester, when organogenesis is completed with the exception of the brain and the gonads, the risk of fetal abnormalities is low, and intrauterine growth retardation and preterm birth are the principal effects
timing of chemotherapy and delivery• Finally, the timing of chemotherapy and delivery is an important issue.• The mother should not give birth within 2 weeks of the last treatment as myelosuppression with pancytopenia is expected to be maximal at this time. I• t is also known that the placenta helps to eliminate drugs in a fetus while a newborn may not be able to metabolise the agents leading to harmful toxicity.• Furthermore, delivery shortly after chemotherapy exposes health care personnel to contaminated blood and amniotic fluid.
• 17 patients with pregnancy-associated ovarian cancer were reported from the M. D. Anderson Hospital in Houston, Texas from 1954 to 1970. – 53 percent were epithelial carcinomas, – 29 percent dysgerminomas, – 12 percent granulosa cell tumors, and – 6 percentembryonal carcinoma
• Ovarian cancers diagnosed in pregnancy are associated with a better maternal prognosis because they are more likely to be of lower stage• This finding can be attributed tothe natural behavior of tumor sub-types more commonly seen in the younger, pregnant population
• Because it is such a rare diagnosis, there is an absence of well-designed studies in the literature that outline the optimal management of pregnant patients with ovarian cancer. Several recent reports describe good fetal outcomes with conservative surgical management to allow pregnancy progression
Conclusions• Ovarian cancer during pregnancy is a rare diagnosis• The literature supplies reviews of small series with mixed pathologies from which evidence for treatment cannot be deduced.• Reviewers have implied that it is usually possible to manage the patient with the best fetal outcome. But evidence of this as altering the prognosis of the disease cannot be extrapolated from the articles discussed• The safety of debulking procedure after 16-18 weeks have been shown but the effect of chemotherapy is still understudied.• It is unwise to import conclusions about management as they involve issues pertaining to fetus viability ( an issue that is locally determined).