Discussion
Owing to the current trend of delaying pregnancy into the later reproductive years and the increased availability of screening tests for cervical cancer, physicians caring for pregnant women may encounter early-stage cervical cancer more frequently. If there is a concern with the appearance of the cervix or problems of interpretation, women should be referred for colposcopic assessment. This should be performed by an experienced colposcopist. Colposcopy is safe in pregnancy, as cervical punch biopsy is. In addition to the assessment of the extent of the cancer (staging), the initial evaluation of the pregnant patient with cervical cancer should include an accurate appraisal of gestational age and thorough ultrasound examination of the fetus. Care should also be taken to screen for aneuploidies and fetal anomalies, during the appropriate time intervals. Once the diagnosis, stage, and extent of invasive cervical cancer have been established in the pregnant patient, a multidisciplinary meeting should be arranged with representatives specializing in gynecologic oncology, maternal-fetal medicine, neonatology, and oncology. The decision to delay or initiate treatment has ethical, moral, and cultural implications that need to be carefully addressed.[9]
Immediate definitive treatment, regardless of gestational age, is generally appropriate in case of locally advanced disease and documented lymph node metastases and depends on the patient's choice or progression of disease during the pregnancy.[10] If the mother chooses to continue the pregnancy, decisions regarding timing of treatment and delivery require careful consideration of disease stage and the trimester in which the diagnosis is made.
In general, treatment guidelines for pregnant patients with invasive cervical cancer are similar with those for nonpregnant patients. Owing to the absence of prospective clinical trials, the management of cervical cancer during pregnancy remains unclear and varies according to the stage of disease and gestational age at diagnosis. During the second half of the pregnancy, a delay of 6 to 8 weeks to reach fetal lung maturity is acceptable. However, during the first half of pregnancy, when delivery is remote, women are advised to be treated as soon as possible, relinquishing their pregnancy.[11]
As in case 1, a stage IB1 cervical cancer at 16 weeks of gestation, whose patient decided to terminate the pregnancy, a radical hysterectomy with ovarian preservation and pelvic lymphadenectomy was performed. This is the standard management for stage IB1 cervical cancer up to 20 weeks of gestation and is recommended as a management option.[12] Radical hysterectomy has been proven to be an effective curative treatment for early-stage cervical cancer at the expense of the pregnancy.[13]
Alternatively, radiation therapy can be initiated, usually leading to pregnancy termination, or medically induced uterine evacuation is also possible.
In cases 2 and 3 where there was the explicit wish to preserve the pregnancy, tumor size and stage were crucial determinants for the delaying of the definite treatment. The limited experience with invasive cervical cancer diagnosed during pregnancy renders every proposed treatment investigational. For those patients who choose to delay treatment, close tumor surveillance is warranted. Regular pelvic examinations, with visual inspection and colposcopic evaluation, may assist in the detection of tumor progression during the period of planned delay. Duggan et al.[10] advocate the use of serial MRI in the assessment of tumor size and spread.
Delaying definitive treatment to improve fetal outcome, although beneficial to the fetus, may carry an additional risk of tumor progression. A delay in definitive treatment is regarded as feasible and safe in patients with small-sized tumor and early-stage disease, if there is no evidence of disease progression.[14] The goal is fetal viability. Several lines of evidence support this approach. In nonpregnant women, it is common to allow a 6-week interval between diagnostic conization and definitive surgery; this delay has not been associated with adverse effects on outcome. Furthermore, a review of 98 pregnancies in which therapy for cervical cancer was deliberately delayed for 3 to 40 weeks provided reassuring data.[15] At the last follow-up, 93 patients (96%) were alive with no evidence of disease. All 98 patients had stage I to II diseases, and most had very early-stage disease (stage IA and small-volume stage IB1), for which there is only a small risk of clinically significant disease progression. These results emphasize the possibility of preserving pregnancy and delaying treatment for more than the accepted 6 to 8 weeks, even during the first and second trimesters of pregnancy. However, because these studies that deal with a small number of patients are limited and a real concern for the patient's outcome exists, active management will usually be preferable.
Alternatively, neoadjuvant chemotherapy (NACT) during pregnancy can be used to stabilize or reduce cervical cancer.[15–17] Bulky and locally advanced cervical cancer in nonpregnant women is sometimes treated with NACT because it can lead to clinically significant tumor shrinkage and thus increasing operability. Radical hysterectomy is performed after NACT. Neoadjuvant chemotherapy has been attempted in pregnant women with locally advanced cervical carcinoma, who were unwilling to undergo either pregnancy termination or a therapy likely to result in fetal death. The goal of NACT was to achieve disease regression or stabilization until the fetus could be safely delivered. However, only 9 such cases have been reported, 2 patients of which with stage IB1,[16,18] with the use of NACT currently being evaluated and principal indications limited to locally advanced carcinomas or localized (stages IB or IIA) bulky tumors.
Cesarean delivery is recommended for patients with stage IA2, IB, or IIA disease. A radical hysterectomy and pelvic/para-aortic lymphadenectomy can be performed as soon as the infant has been delivered and the hysterotomy closed. Cesarean-radical hysterectomy is more associated with greater blood loss and need for blood transfusion than is radical hysterectomy in nongravid women.[11,19,20] In case 2, technical difficulties led to separate procedures (cesarean and radical hysterectomy); nevertheless, the benefit of 1 surgical procedure (cesarean-radical hysterectomy) outweighs the disadvantage of increased blood loss, as performed in case 3.
Radical trachelectomy with lymphadenectomy 6 to 8 weeks after childbirth is an alternative to radical hysterectomy for selected women with stage IA2 or small-volume stage IB1 disease, in whom fertility preservation is desired.[21,22]
Radical trachelectomy has also been described by Ungar et al.[23] during pregnancy. This procedure is technically hazardous, associated with large volumes of blood loss and a considerable high-risk pregnancy loss. The following cases were poorly differentiated carcinomas of a woman, grade 3 (cases 1 and 2), or the lesion was more than 2.5 cm (case 3), thus not accepted for conservative therapy.
Given the limited number of systematic case series in the literature comparing the treatment of cervical cancer in both pregnant and nonpregnant women, it is difficult to draw definitive conclusions on how the overall prognosis differs. It does seem, however, that these women have a survival profile that closely approximates the nonpregnant population, when adjusted for stage.[6,7,11,14,24,25] The effect of cervical cancer on pregnancy outcome is less clear.[6,11,24]
In conclusion, in an early-stage cervical cancer diagnosed in the first half of pregnancy, a delaying treatment to minimize fetal/neonatal risks can be proposed under strict conditions. These include an explicit wish to preserve the pregnancy and favorable obstetrical and oncological prognostic factors.
J Low Genit Tract Dis. 2013;17(1):66-70. © 2013 Lippincott Williams & Wilkins
