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5.6 Carcinoma of the Cervix in Pregnancy

Disease in the pregnant woman is generally managed as in the non-pregnant woman. The treatment policies must be individualized as to the stage and extent of disease, gestational age and, in particular, the wishes of the patient by the multidisciplinary team.

In the case of a high risk Pap smear, colposcopy should be performed. Colposcopic guided biopsy of suspicious areas is recommended only if there is clinical suspicion of malignancy. An ECC should not be performed during pregnancy. If there is no clinical suspicion for malignancy, colposcopy should be repeated every trimester and again 2-3 months post- partum. 

Should invasive carcinoma be discovered in early pregnancy and thought to be unsuitable for primary surgical therapy, termination of the pregnancy is usually carried out with the method depending on the gestational age and is followed by radiotherapy +/- chemotherapy. Patients with suspected clinical stage IA1 disease may be treated primarily with a cone biopsy. This should be performed after the first trimester to minimize complications and risks to the pregnancy. 

If more advanced disease is suspected, options for management include radical hysterectomy with fetus in situ and pelvic lymphadenectomy, or delay of definitive treatment to allow for fetal maturity. In the latter situation, neoadjuvant chemotherapy during the pregnancy should be considered. For those patients diagnosed in the latter stage of pregnancy with a viable fetus, delivery by caesarean section is usually recommended although studies have not shown that vaginal delivery has produced a higher morbidity or decreased survival in patients delivered this way. 

Radiotherapy

Primary Radiotherapy
Pelvic +/- para-aortic radiotherapy to a dose of 45-50 Gy in 1.8-2 Gy per fraction is recommended. Gross pelvic or para-aortic lymph nodes (or PET positive nodes) should receive a dose boost, using simultaneous integrated boost or sequential technique. Pelvic radiotherapy only is recommended in cases with negative nodes.  Para-aortic irradiation is recommended in cases with positive para-aortic nodes and can be considered in cases of positive pelvic nodes.

External beam radiotherapy must be followed by intracavitary +/- interstitial brachytherapy unless contraindicated for medical reasons. Interstitial technique to augment intracavitary brachytherapy must be considered in cases of large tumors, asymmetrical tumors, significant lateral extension and unfavorable anatomy. CT-guided brachytherapy planning must be done. MRI-guided brachytherapy planning should be considered for all cases, having shown increased local control and decreased toxicity in large cohort studies. The MRI should be done for at least one fraction, usually at the first insertion, with applicators in place. Target volumes and organs at risk, including bladder, rectum, sigmoid and bowels, should be contoured and volumetric dose prescription must be done.

In cases of extensive persistent disease at the time of brachytherapy, an additional external beam boost can be considered.

Radiation treatment including external beam and brachytherapy should be completed within 56 days with the goal of completing the treatment in the shortest time possible.

Adjuvant Radiotherapy
Pelvic radiotherapy to a dose of 45-50Gy in 1.8-2Gy per fraction is recommended, with or without brachytherapy boost.

Chemotherapy

Primary Concurrent Chemo-Radiation
Results from each of five randomized phase III trials show an average overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy. Although the trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, they all demonstrate significant survival benefit for this combined approach. The protocol designation for this therapy is GOCXCRT. It consists of weekly cisplatin at 40 mg/m2 weekly for five weeks during external beam radiation therapy.

Advanced or Recurrent Disease
Palliative treatment may be offered in the form of standard chemotherapy or as part of investigatory protocols.  In the first-line setting, our current standard is carboplatin, paclitaxel, and bevacizumab (GOCXCATB).  Palliative chemotherapy incorporating bevacizumab has been shown to improve overall survival.

There is no evidence that treatment in the second- or later-line setting improves overall survival, compared with best supportive care alone.

For more information on chemotherapy protocols, please click here.

References

  1. Tang J, et al. Chemoradiation and adjuvant chemotherapy in advanced cervical adenocarcinoma. Gynecol Oncol 2012;125:297-302.
  2. Tewari K, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014;370:734-43.

Estrogen Replacement Therapy

No data exists to show a contraindication for hormone replacement in cervical or vaginal cancer. Many of these patients are young and at high risk for estrogen deprivation related morbidity. It is common practice to encourage such patients to take estrogen replacement therapy. There are a multitude of choices but in the presence of a uterus, it is recommended to use continuous estrogen and progesterone with the estrogen at a moderate dose (Estradiol 2mg po daily or Estradot patch 50mcg change twice a week) and the progesterone at a low dose (2.5 mg Provera). Histologic studies have shown that continuous therapy with combined estrogen and progesterone induces an atrophic bland endometrium. This regime may result in some initial bleeding for the first one to two months but in general the women are amenorrheic.
 
An alternative regime would be to use cyclical estrogen and progesterone. This has the disadvantage of inducing a withdrawal bleed in some patients who have not had total ablation of the endometrium. Hematometra may develop if there is cervical stenosis present leading to abdominal pain or a mass.

Transdermal estrogen replacement therapy is associated with a lower risk of thromboembolism, stroke and hypertriglyceridemia compared to oral estrogen preparations. However, an oral preparation is a reasonable option for women with low risk of thromboembolic events. 

Recommendation: Continuous estrogen and progesterone, e.g.:
Micronized 17-beta estradiol 1-2mg taken daily, 50mcg of transdermal estradiol (Estradot Patch) to be changed twice a week (eg Monday and Thursday) or Conjugated Estrogen (Premarin) 0.625-1.25mg taken daily

Provera 2.5 mg daily
(note: these small doses of Provera do not seem to have the same deleterious effects on serum lipids as the higher doses.)

In the absence of a uterus estrogen alone in usual doses is recommended.


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