Download BIOETHICS: For Allowing Fetal Viability prior to Hysterectomy

BIOETHICS: For Allowing Fetal Viability prior to Hysterectomy
STENCHEVER COMPREHENSIVE GYNECOLOGY, 5th ed, 2007
TABLE 29-2 -- Carcinoma of the Uterine Cervix: Distribution by Stage and 5-Year Survival Rates for Patients Treated in 1990–
1992 (n = 11,945)
Stage
Patients (n)
5-Year Survival
Stage la
902
95.01%
Stage lb
4657
80.1% (generally high survival rate)
Stage II
3364
64.2%
Stage III
2530
38.31%
Stage IV
492
14%
Modified from Pecorelli et al: Annual report on the Results of Treatment in Gynaecological Cancer, XXIII Volume, Milan, 1998.
Federation Internationale de Gynecologie et d'Obstetrique.
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Within each stage, survival statistics are similar in pregnant and nonpregnant women.
If vaginal delivery, high risk for tumor dissemination and hemorrhage. But if Cesarean section, no increased in
risk.
If carcinoma is diagnosed in the first trimester or early in the second trimester (before 20 weeks), treatment may
be undertaken immediately because of the concern that a delay could lead to tumor progression or spread.
However, Duggan et al. had delays of 2 to 7 months in 8 pregnant patients with stage I disease and
demonstrated no adverse effects from the delay.
For patients beyond the twentieth week of gestation, therapy is often delayed until fetal viability. The health and
maturity of the fetus are determined by appropriate ultrasound studies and amniotic fluid analysis to ensure
fetal lung maturity. Delivery is usually accomplished by cesarean section, and after this, therapy is completed by
operation or radiation with the usual considerations of tumor stage and size.
Overall, treatment results in pregnant patients are similar to those in nonpregnant patients, stage for stage, as
recently confirmed by van der Vange et al. Overall, a 5-year survival rate of 49.2% was recorded for pregnant
patients, in comparison to 51% for nonpregnant patients treated during the same period of time.
JOURNAL ARTICLE
N. Germann, C. Haie-Meder, P. Morice, C. Lhomme, P. Duvillard, K. Hacene & A. Gerbaulet. Management and clinical outcomes
of pregnancy and invasive cervical cancer. Annals of Oncology 16: 397–402, 2005
Background: The objective of this study was to evaluate the clinical outcomes and to discuss the management of women
presenting with an invasive cervical cancer during pregnancy. Patients and methods: We retrospectively reviewed patients
treated for an invasive cervical cancer diagnosed during pregnancy between 1985 and 2000 in our institution.
Results: Twenty-one pregnant patients among a total of 487 women were treated. Thirteen, five, two and one, respectively,
were diagnosed during the first, second and third pregnancy trimester and post-partum. The FIGO stage was IB in 15 cases, IIB
in five cases and IVA in one case. Mean follow-up was 64 months (range 2–165). Overall and disease-free survival at 5 years
were 82% and 79%, respectively. All five patients diagnosed in the second trimester were alive. Two of the 13 patients and one
of the two patients diagnosed during the first trimester and the third trimester, respectively, died of their disease. No
difference was observed between the nine patients whose treatment was delayed or not.
Conclusions: Invasive cervical cancer during pregnancy is rare but is a dilemma for women and their physicians. The present
study and review of the literature suggest that pregnancy does not seem to influence the prognosis of cervical cancer. Delayed
treatment could be proposed to selected patients diagnosed at the end of the second trimester or at the beginning of the third
trimester, with a small tumor (<2 cm) and negative nodes, after a multidisciplinary approach.
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Design: retrospective study of cases from 1985-2000 treated in Institute Gustave-Roussy, Villejuif, France
N = 21, patients who are pregnant and diagnosed with cervical CA with > 5mm invasion (St IA2 and above)
Characteristics
o Age – 28-43, median 33
o Median parity – G1
o Type – Squamous cell CA 20. AdenoCA – 1
o FIGO stage – IB1 14, IIB 5, IB2 1, IVA 1
o Trimester at diagnosis – First 13, Second 5, Third 2
o Delay in therapy – 4 months
o Follow up time -64 months
o Drop out – 2 (lost to follow-up)
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Outcomes of children
Among the 21 patients, a total of 11 viable children were born. The most frequent mode of delivery was by Cesarean
section, in eight patients. Despite an emergency Cesarean section, the child died of fetal cardiac distress in one patient. Three
patients had a vaginal delivery without complications. The range of gestations was 4–9 months. No abnormalities or
malformations were reported in the 10 newborns. Pregnancy was interrupted for therapeutic purposes in four women (median
term 1–3 months). Four fetuses were removed at the time of surgery (median term 1–5 months). There was one spontaneous
abortion. One vaginal delivery resulted from the expulsion of a dead fetus after external beam radiotherapy (patient with stage
IVA disease).
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Fourteen patients are disease-free. Four patients died oftheir cancer (four pelvic recurrences associated with
metastases in two cases).
Overall and disease-free survival were 89% and 79%, respectively, at 3 years and 82% and 73% at 5 years.
All patients with stage I were disease-free and the 5-year survival rate was 80% for the five patients with stage II
disease. The patient with stage IVA died of her disease 39months after the diagnosis.
All 15 patients with a tumor measuring <4 cm were alive and free of disease at 5 years. When the tumor size was
>4 cm, 5-year survival was 60%.
Five-year survival was 100% and 84%, respectively, whether the treatment was delayed or not.
Five-year survival was 90% for the 13 patients in whom disease was diagnosed during the first trimester. All five
patients in whom disease was diagnosed during the second trimester were alive at 5 years. Two of the three
patients whose tumor was diagnosed during the third trimester and post-partum died of their disease.
Five-year survival was 100% and 90%, respectively, for vaginal delivery (three patients) and Cesarean section
(eight patients).
The majority of the studies in the literature do not report on a difference in the prognosis of invasive cervical
cancer during pregnancy [8–14]. Zemlickis et al. [7] compared 34 women with invasive cervical cancer with 89
non-pregnant controls matched for age, calendar year of diagnosis, stage and tumor type. Pregnancy did not
affect the survival of women with invasive cervical cancer. Other authors reporting on patients with advancedstage disease reached the same conclusions [14–17]. Baltzer et al. [8] found no differences in tumor size,
histologic differentiation, lymphatic invasion and lymph node metastases between pregnant and non-pregnant
women.
The majority of papers suggested that treatment of the tumor could be delayed, particularly in patients with
early-stage disease. Only three series do not support this proposed recommendation [19, 22, 25]. Dudan et al.
[22] reported two clinical progressions in patients with stage IB disease. Nisker and Shubat [19] and Monk and
Montz [25] reported the death of two patients with stage IB disease after delayed therapy (24 and 3 weeks). In
our experience, postponing therapy had no influence on survival in nine patients. The percentage of positive
nodes in these nine patients was 33%, and patients whose treatment was delayed had a better prognosis (small
tumors) than the others, but no disease progression was observed during pregnancy. However, definitive
conclusions about the impact on the survival of pregnant patients of delay in treatment could not be reached in
the present study because of the small number of patients in whom treatment was delayed (nine patients).
COHORT STUDY
The Prognosis of Cervical Cancer Associated With Pregnancy: A Matched Cohort Study
VANGE, N. VANDER; WEVERLING, G. J.; KETTING, B. W.; ANKUM, W. M.; SAMLAL, R.; LAMMES, F. B.
Abstract
Objective: To assess the effect of pregnancy on the prognosis of cervical cancer and the morbidity of standard treatment.
Methods: We analyzed 44 women with cervical carcinoma associated with pregnancy, who were matched with 44 controls.
Matching criteria were age, stage of disease (according to the International Federation of Gynecology and Obstetrics
classification), tumor type, treatment modality, and period of treatment.
Results: In 23 cases, cervical cancer was diagnosed during pregnancy and in the other 21 cases, within 6 months after delivery.
Thirty-nine women had early-stage disease (eight IA, 25 IB, and six IIA), and five had advanced stages (four IIB and one IIIB). The
overall 5-year survival rate was 80% among subjects and 82% among controls, whereas the relative risk (RR) of dying within 5
years was 1.12 (95% confidence interval [CI] 0.48-2.65). With regard to the 5-year survival rate (85% for both subjects and
controls, the RR of dying was 1.00 [95% CI 0.35-2.83]); no differences were found between subjects and controls for early-stage
cervical carcinoma. The size of the group with advanced-stage cervical carcinoma was too small to allow any statistical analysis.
No statistically significant differences in survival were observed between cases diagnosed during pregnancy and cases
diagnosed after delivery. In addition, the mode of delivery had no effect on survival. Early complications within 6 weeks after
treatment were seen 33 times in 25 subjects and 29 times in 23 controls. No differences were observed in the prevalence and
type of early complications in subjects versus controls. Late complications after 6 weeks of treatment were seen nine times in
nine subjects and 11 times in ten controls. No significant differences were observed in the prevalence and type of late
complications in subjects versus controls.
Conclusion: The prognosis of early-stage cervical cancer is similar in pregnant and nonpregnant patients when standard
treatment is given. Because of the limited number of patients, no conclusions can be drawn about advanced-stage cervical
cancer. The goal should be standard oncologic treatment, which does not lead to morbidity in pregant patient.
(C) 1995 The American College of Obstetricians and Gynecologists
CASE REPORT
Successful conservative treatment of endocervical adenocarcinoma stage Ib1 diagnosed early in pregnancy
Authors: KRISTEL VAN CALSTEREN1, MYRIAM HANSSENS2, PHILIPPE MOERMAN3,
GUY ORYE4, DIDIER BIELEN5, IGNACE VERGOTE1 & FREDERIC AMANT1
1Gynecologic Oncology, Leuven Cancer Institute (LKI), Department of Obstetrics and Gynecology, UZ Gasthuisberg, Katholieke
Universiteit Leuven, Belgium, 2Perinatal Center, Department of Obstetrics and Gynecology, UZ Gasthuisberg, Katholieke
Universiteit Leuven, Belgium, 3Department of Pathology, UZ Gasthuisberg, Katholieke Universiteit Leuven, Belgium,
4Department of Obstetrics and Gynecology, Virga Jesse Ziekenhuis, Hasselt, Belgium, and 5Department of Radiology, UZ
Gasthuisberg, Katholieke Universiteit Leuven, Belgium
Abstract
Traditionally when cervical cancer is diagnosed during the first trimester of pregnancy, oncological treatment is given priority
despite the pregnant state. A 32-year-old primigravida was diagnosed with invasive endocervical adenocarcinoma stage Ib1 at 8
weeks’ gestation. As the patient wanted to preserve the pregnancy, an amputation of the anterior cervix and retroperitoneal
pelvic lymphadenectomy were performed. Based on favourable prognostic markers, we decided to maintain the pregnancy
with careful cytological and histological follow-up. The patient gave birth at term to a healthy boy, and 18 months after the
delivery there is no evidence of recurrent disease. In the absence of poor prognostic markers, we decided to adopt a
conservative approach for cervical adenocarcinoma in a pregnant patient at 8 weeks’ gestation.
Discussion
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Factors taken into consideration include the stromal invasion, largest tumour diameter, histological features and
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nodal status.
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Successful conservative treatment of endocervical adenocarcinoma 251 including lymphadenectomy, should be
performed prior to offering a conservative approach.
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Conisation, cervical amputation (large cone) and radical trachelectomy have been described as fertility-conserving
surgery, and can also be applied when the aim is the maintenance of pregnancy.
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Conisation is the standard treatment for stage Ia1 cervical cancer in non-pregnant women who want to preserve their
fertility, and can be applied during pregnancy. The most frequent complications of a conisation during pregnancy are
haemorrhage (5_10%), miscarriage (25%), preterm labour and delivery as well as infection.
To minimise the risk of miscarriage and blood loss, the optimal time for cervical conisation is the second trimester,
preferably between 14 and 20 weeks’ gestation (1).
For larger lesions, individualisation is necessary: Radical trachelectomy (but the procedure is technically hazardous,
associated with large volumes of blood loss and a considerable high risk of pregnancy loss) and neoadjuvant
chemotherapy during pregnancy can be used to stabilise or reduce cervical cancer (2_4).
Chemotherapy can be administered until fetal viability, at that stage the delivery and definitive surgical treatment of
the cancer (conisation or radical hysterectomy depending on the remaining tumour volume) can be performed.
Most centres accept a tumour size B20 mm as limiting criterion for fertility-sparing surgery (5). This size takes into
consideration the achievement of a tumour-free margin of approximately 10 mm, and sufficient residual functional
cervical stroma.
Tumour biology will also determine the potential to maintain the pregnancy.
Pelvic nodal status, however, is the most important prognostic factor in early stage cervical cancer.
The existence of lymph nodes in the parametrium that might contain metastatic cells is the rationale for
parametrectomy in a Wertheim_Meigs procedure.
The documentation of a negative nodal status, including the parametrial nodes, was necessary to accept a
conservative approach. Positive nodes would characterise high risk disease necessitating standard treatment for
cervical cancer. In this case, a radical hysterectomy with loss of the pregnancy would have been performed.
The route of delivery will be determined by the presence or absence of tumour. In case of tumour activity at the time
of the delivery, a caesarean section is the preferred route of delivery to prevent (fatal) recurrences in the episiotomy
scar (10,11).
We conclude that in cases of early stage cervical cancer diagnosed in the first trimester of pregnancy, a conservative
surgical approach can be proposed under strict conditions. These include an explicit wish to preserve the pregnancy
and favourable obstetrical and oncological prognostic factors.
CASE REPORT
Pregnancy after neoadjuvant chemotherapy followed by pelvic lymphadenectomy and radical trachelectomy in bulky stage
IB1 cervical cancer: A case report
Hua LIU, Zhi-lan PENG, Jiang-yan LOU and Wang PING Department of Obstetrics and Gynaecology, West China Second Hospital,
Sichuan University, Chendu, Sichuan, China
A 24-year-old G4P0 patient with seven months of abnormal genital bleeding was presented. Physical examination revealed that
a tumour was present at the left underside of the cervix, which measures 2 cm in size and extended almost to the left vaginal
fornix with no infiltration of the parametrium or vagina. Cervical biopsy confirmed a poorly differentiated squamous cell
carcinoma without vascular space invasion. This case was classified as a FigO stage IB1. The patient wanted to preserve her
fertility potential, and for this reason, we offered her one cycle of chemotherapy with bleomycin + cisplatin (BP) intravenous
regimen: bleomycin 15 mg/m2 on days 1–2 and cisplatin 70 mg/m2 on day 1 with continued
hydration. Ten days later, she underwent transabdominal pelvic lymphadenectomy. After all lymph nodes were confirmed
negative through frozen section, abdominal RT was completely followed. After operation, the cervical canal was 0.3–0.5 cm in
length below the isthmus. On final pathology, only focal carcinoma (5.5 mm in width and 3 mm in depth) remained on the
cervical vaginal side. The patient recovered well and was followed up. Two years later, she conceived and gave birth through
cesarean section after 35+2 gestational weeks because of intrahepatic cholestasis of pregnancy. The newborn weighing 2600 g
and with no evidence of abnormalities had Apgar scores of 10 and 10 at one and five minutes, respectively. To assess the
stability of the cervix, transvaginal ultrasound measurement of cervical length was performed at 16, 28 and 35 weeks of
gestation, and no significant cervical shortening was observed throughout the pregnancy.