Case Conference July 3th 2018

03-Jul-2018, Divisi Ginekologi Onkologi RSCM

CASE CONFERENCE

July 3^th, 2018

Mrs. Lulu Marendang, 35 yo, G3P2A0, 429-33-13

Invasive cervical cancer in pregnancy

PPDS: Syifa M. Syafitri (T3B, Oncology Rotation)

Supervisor: dr. Tricia Dewi Anggraeni, OBGYN(C)

 

CASE DESCRIPTION (April, 3th 2018)

Mrs LM, G3P2, presented to emergency room RSCM with complained of vaginal bleeding at 8 months of pregnancy. Previously, she came to Taman Harapan Baru Hospital and diagnosed with G3P2, 33-34 weeks, post CS 1x, PROM then referred to RSCM. In RSCM, the patient diagnosed with G3P2, 33-34 weeks, post CS 1x, preterm labor, superimposed preeclampsia, suspected cervical polyp. She has hypertension since 2 year and controlled with nifedipin 1x10 mg. There were history of contact bleeding history and fluor albus. On examination found nodulated mass on the cervix, soft consistency, suspected cervical polyp. After tocolytic, lung maturation and MgSO4 administration, she underwent cesarean section - tubectomy and cervical mass biopsy (on April, 5th 2018). The baby boy was born, 1910 gram, 41 cm, A/S 8/9. Results of cervical mass biopsy histopathology: moderate differentiation unkeratinized squamous cell carcinoma, without lymphovascular invasion.  

On evaluation after delivery, her general status was within normal limit. On speculum examination found smooth cervix, with papillary mass on 10-11 o’clock direction. From bimanual examination palpated smooth cervix, unpalpable mass on the cervix, and uterus  was within normal limit. Ultrasound finding shows no sign of malignancy and abdomino-pelvis mass or metastasis. She was diagnosed as cervical cancer stage IB1. The patient then underwent laparoscopy radical hysterectomy and bilateral pelvic lymph node dissection on June, 28^th 2018.

 

 

 

Figure 1. Inspeculo finding on evaluation after delivery

INTRODUCTION

Cervical cancer is one of the most common malignancies in pregnancy, with an estimated incidence of 0.8 to 1.5 cases per 10,000 births. One to 3 % of women diagnosed with cervical cancer are pregnant or postpartum at the time of diagnosis. Half of these cases are diagnosed prenatally, and the other half in the 12 months after delivery.

Most patients are diagnosed at an early stage of disease. This is probably due to routine prenatal screening and that advanced stage disease will interferes with conception. Stage, course of disease and prognosis of cervical cancer in pregnant patients are similar to those of nonpregnant.

There are no large randomized trials data to base recommendations for the care of pregnant patients with cervical cancer. Therefore, management is based upon evidence from randomized trials in nonpregnant women, findings from observational studies of pregnant women, and the unique considerations of each individual case. Treatment should be individualized and based on the stage of cancer, the woman's desire to continue pregnancy, and the risks of modifying or delaying therapy during pregnancy.

 

QUESTION

How are the management of invasive cervical cancer in pregnancy?

 

LITERATURE REVIEW

A careful multidisciplinary team approach is required and the desires of the pregnant patient (and her family) regarding preservation of the pregnancy should be considered. Immediate, definitive treatment, regardless of gestational age, is generally appropriate in:

§ Documented lymph node metastases

§ Progression of disease during the pregnancy

§ Patient choice to terminate the pregnancy

 

Figure 2. Algorithm for the treatment of cervical cancer in pregnancy

IF PREGNANCIES NOT TERMINATED 

Management of cervical cancer in women who do not choose or are unable to terminate pregnancy requires individualized consideration of stage of disease, treatment options, patient preferences, and fetal viability. Radiation therapy (RT) is contraindicated as it can cause fetal demise or serious nonlethal fetal harm. Approach is placed based on fetal gestational age and the International Federation of Gynecology and Obstetrics (FIGO) stage of cervical cancer at diagnosis.

· Gestational age less than 22 to 25 weeks at diagnosis — patients suggested to undergo lymphadenectomy if it can be performed safely. Limited data indicate that lymphadenectomy can be performed in the first and most of the second trimester with no increased risk of complications.  

o No evidence of nodal involvement:

§ Microinvasive disease (Stage IA1) — conization. This appears to be sufficient and relatively safe. In a report of eight pregnant women, no disease progression was documented before definitive therapy.

The patients should aware that cervical conization may be associated with significant morbidity and perinatal complications,: excessive bleeding ranging from 5 to 15 percent and a risk of spontaneous abortion. Because of these, some advocated the use of a coin excision to cause less disruption to the endocervical canal.

§ Stage IA2 to IB1 tumor <2 cm —the reported risk of parametrial extension is less than 1 %. Therefore, conservative surgical options, including a simple trachelectomy or large conization, are appropriate. Radical trachelectomy should be avoided if pregnancy preservation is desired (32 %  incidence of spontaneous abortion).

§ Stage IB1 (tumor 2 cm or larger) and higher —neoadjuvant chemotherapy if they have no evidence of lymph node involvement on lymphadenectomy. Neoadjuvant chemotherapy can be administered without prior staging lymphadenectomy, in which case, surgical staging should be performed six to eight weeks after delivery.

o Positive nodal involvement — Patients with evidence of nodal involvement, confirmed on lymphadenectomy or suspected based on imaging findings, have advanced cervical cancer.

§ If she wish to preserve their pregnancies, treatment options include neoadjuvant chemotherapy or early delivery. The approach to these patients is similar to women with advanced disease in whom pregnancy preservation is not desired.

· Gestational age 22 to 25 weeks or later —lymphadenectomy becomes less of an option due to the increased risks associated with surgery and the size of the pregnant uterus. Decisions on treatment should be based on the clinical stage of disease at diagnosis.

 

o Stage IA to IB1 tumor <2 cm —delaying treatment until six to eight weeks after delivery. Several lines of evidence support this approach:

§ In nonpregnant women, it is common to allow a six-week interval between diagnostic conization and definitive surgery. This delay has not been associated with adverse effects on outcome.

§ A review of 98 pregnancies in which therapy for cervical cancer was deliberately delayed for 3 to 40 weeks to allow fetal maturation also provided reassuring data. All 98 of the patients had stage I to II disease, and most had very early stage disease (stage IA and small volume IB1), for which there is only a small risk of clinically significant disease progression.

§ Should disease progression be observed, treatment may become necessary. The approach is similar to patients presenting at an earlier gestational age and with evidence of nodal involvement.

o Stage greater than IB1 (Tumor 2 cm or larger) — For women with a larger tumor ≥2 cm, there is a lack of data on treatment delay and outcomes. Some oncologists have suggested that treatment not be postponed for patients with tumors exceeding 4 cm, also includes patients with positive lymph nodes. If the patient prefers not to deliver early, we would advocate for the administration of neoadjuvant chemotherapy until delivery rather than a delay of treatment.

 

Surveillance during pregnancy —The surveillance strategy is dependent on the extent of disease:

§ Women with stage IA1 disease are followed with clinical examinations and colposcopy each trimester throughout pregnancy.

§ For women who elect to delay definitive therapy until after delivery and for those patients who are on neoadjuvant chemotherapy, we recommend proceeding with a pelvic examination every three to four weeks during pregnancy. In addition, repeat imaging using magnetic resonance imaging (MRI) without gadolinium should be performed to rule out disease progression. These women should be followed by a maternal-fetal medicine specialist in order to ensure close maternal surveillance and monitoring of fetal growth and well-being.

 

Considerations about delivery — The timing of delivery must be individualized based on the gestational age of the fetus, the stage of the cervical cancer, and whether the tumor shows evidence of disease progression during the pregnancy. A term delivery at ≥37 weeks and ideally at 39 weeks is optimal; however, if earlier delivery is indicated for medical or obstetrical reasons, steroids may be administered to reduce the morbidity of preterm birth.

No randomized trials evaluating maternal outcome according to mode of delivery are available.

§ Retrospective and case-controlled studies suggest that vaginal delivery through a cervix with microscopic cervical cancer generally does not alter maternal prognosis. Women with stage IA1 and IA2 cervical cancer can proceed with a vaginal delivery, with cesarean delivery reserved for standard obstetrical indications. Episiotomy should be avoided when possible. At least 15 cases of tumor cell implantation in the episiotomy site have been reported after vaginal birth in women with cervical cancer. Five of the 11 patients who had recurrence of cervical cancer in the episiotomy site died of their disease.

§ For women with stage IB1 or greater cervical cancer, vaginal delivery should be avoided. The limited data suggest that maternal cancer outcomes are worse with vaginal rather than cesarean delivery. Furthermore, patients with bulky or friable gross tumor and those with barrel-shaped cervical cancer are at risk for significant hemorrhage and obstruction of the birth canal during labor and attempted vaginal delivery. Thus, it is prudent to schedule a cesarean delivery once fetal maturity is likely, ie, at least ≥37 weeks and ideally at 39 weeks.

 

Definitive treatment for cervical cancer — For women who opted to continue their pregnancy, the definitive treatment of cervical cancer can occur at the time of delivery or postpartum. Our approach is as follows:

§ For women who wish to preserve future fertility:

No further treatment is warranted if they had stage IA1 disease, if no further evidence of disease during follow-up. If the conization margin was positive, delivery by cesarean and repeat conization six to eight weeks postpartum to rule out invasive disease is indicated.

Radical trachelectomy (with lymphadenectomy if not already performed) is indicated if they had stage IA2 disease or a tumor up to 4 cm in size. This can be performed six to eight weeks after delivery.  

§ For women who do not wish to preserve fertility:

Those patients with stage IA1 disease without evidence of LVSI are candidates for an extrafascial hysterectomy. This may be done concomitantly with a cesarean delivery.

Patients with stage IA1 with LVSI, IA2, or IB1 tumors <2 cm should undergo definitive treatment with radical hysterectomy, which can be done at the time of cesarean delivery or as a second surgical procedure postpartum.  

§ Patients treated with neoadjuvant chemotherapy during pregnancy for locally advanced disease or node-positive disease should undergo a radical hysterectomy

 

WOMEN WITH METASTATIC DISEASE 

Patients with evidence of disease outside of the cervix involving other organs have stage IV cervical cancer. The prognosis associated with metastatic cervical cancer is poor, and pregnancy is expected to make the situation even more psychologically and emotionally difficult for the patient and her family. It is important that the psychosocial needs of women in this situation be actively addressed, even while a treatment plan is developed. For women with metastatic cervical cancer in pregnancy, the management is medical and aimed at disease control, not cure. Therefore, these women should be offered chemotherapy with agents in use for women with metastatic or recurrent cervical cancer who are not pregnant. The chemotherapy agents of choice (cisplatin and paclitaxel) can be initiated during pregnancy.

 

SYSTEMIC THERAPY IN PREGNANCY 

§ The regimen of choice is the combination of cisplatin plus paclitaxel administered every 3 weeks for a maximum of six cycles. There is some evidence that cisplatin is filtered by the placenta. In a study of 21 pregnant women with cervical cancer, platinum concentrations in the amniotic fluid at delivery were only 11 to 42 %. However, low albumin levels in pregnancy result in higher levels of free cisplatin in the mother and fetus and may increase the risk of toxicity, including ototoxicity. Transient neutropenia in the newborn has also been reported.

§ Ideally, there should be three weeks between completion of chemotherapy and delivery, so the bone marrow can recover and to allow the placenta to metabolize and eliminate cytotoxic drugs from the fetus. Since the potential for spontaneous labor increases, it is prudent to avoid chemotherapy in the late third trimester.

§ Data regarding the safety of chemotherapy in pregnancy are limited. The effects of chemotherapy on the fetus depend upon the gestational age, agent(s) used, and dose. A 2013 systematic review of 48 human pregnancy exposures to platinum derivatives for treatment of cervical cancer at 17 to 33 weeks of gestation reported 67.4 percent of neonates were healthy at birth, and the problems in most of the remainder were associated with prematurity (eg, respiratory distress).  

 

CONCLUSION

Multidisciplinary approach is mandatory in cervical cancer diagnosed during pregnancy, since stage, gestational age and patient’s desire to continue the pregnancy will determine the treatment policy. Overall prognosis appears to be similar to the non-pregnant state. In this case, patients with stage IB1 tumors <2 cm already underwent definitive treatment with radical hysterectomy as a second surgical procedure postpartum.  

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