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Fetal and maternal considerations in the management of stage I-B cervical cancer during pregnancy
GYNECOLOGIC
ONCOLOGY
34,
61-65 (1989)
Fetal and Maternal Considerations in the Management of Stage I-B Cervical Cancer during Pregnancy’ B. E. GREER, M.D.,’ T. R. EASTERLING, M.D., D. A. MCLENNAN, M.D., T. J. BENEDETTI, M.D., J. M. CAIN, M.D., D. C. FIGGE, M.D., H. K. TAMIMI, M.D., AND J. C. JACKSON, M.D.* University of Washington, Departments of Obstetrics and Gynecology, and *Pediatrics, Seattle, Washington, 98195 Received March 1, 1988
The timing of treatment for stage I-B cervical carcmoma diagnosed during pregnancy is complicated by conflicting concerns for fetal survival and control of malignancy. There were 11 pregnant women with stage I-B cervical carcinoma diagnosed prior to fetal viability since 1969. Six patients were managed with termination of pregnancy and radical hysterectomy with pelvic lymphadenectomy. In 5 patients, treatment was delayed for 6 to 17 weeks and then delivery was accomplished by cesareansection followed directly by radical hysterectomy and pelvic lymphadenectomy. Two of the infants experienced complicated neonatal courses and would have benefited from additional delay. Benefits that could be achieved by delaying delivery for the fetus were calculated from a review of 600 inborn infants without congenital anomalies admitted to the neonatal intensive care (NICU) during 1984 and 1985. Neonatal mortality decreasedfrom 32.8% at 2627 weeks to 2.7% at 34-35 weeks gestation. Similar improvements in neonatal morbidity were demonstrated. Although adverse maternal outcomes were not associated with delay, an evaluation of risk cannot be derived from this series. Significant fetal benefit can accrue from relatively short delays in planned delivery dates. When stage I-B cervical carcinoma is diagnosed during pregnancy and when fetal survival is desired, delivery should be delayed to achieve fetal maturity, rather than only potential viability. o 1989 Academic
Ress, Inc.
INTRODUCTION Carcinoma of the cervix associated with an intrauterine pregnancy is an uncommon problem. Between 0.02 and 0.4% of pregnancies are complicated by invasive cervical cancer [ 11. Historically, immediate treatment was recommended without regard to the pregnancy. More recently, arbitrary time limits of “fetal viability” have been used without consideration of fetal mortality ’ Presented at the Annual Meeting of The Western Association of Gynecologic Oncologists, May 13-16, 1987. ’ To whom reprint requests for reprints should he addressed.
and morbidity. Highly complex ethical issues, religious beliefs, and emotional considerations for the patient and family are superimposed on this medical dilemma. Both the maternal and the fetal outcomes should be considered when counseling the pregnant patient with invasive cervical cancer. This report attempts to address these issues and offer guidelines for management of both stage I-B cervical carcinoma and pregnancy, when they coexist. MATERIALS
AND METHODS
Between January 1969 and February 1986, at the University of Washington, 11 pregnant patients were treated on the Gynecologic Oncology Service for stage I-B cervical carcinoma. Age, gravidity, parity, methods of diagnosis and treatment, pathology, and maternal and fetal outcomes were considered. To determine the customary interval between diagnosis and definitive therapy at this institution, the records of all patients with stage I-B cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy during 1983 and 1984 were reviewed. None of these patients was pregnant. Expected neonatal mortality and morbidity in premature infants were determined by abstracting data from the University of Washington Neonatal Intensive Care Unit (NICU) database. Six hundred consecutive NICU admissions
since January
1, 1984, representing
inborn
infants without congenital anomalies and with gestational ages between 24 and 35 weeks, were evaluated. Data were grouped by 2-week gestational age spans. Gestational age was determined by the Ballard method [2] and obstetrical parameters. Stillborn infants and those infants that could not be resuscitated in the delivery room were excluded. The incidence of neonatal death prior to discharge, 61 lM9i-h8258189
$1.50
Copyright 0 1989by AcademicPress,Inc. All rights of reproductionin any form reserved.
62
GREER ET AL.
lowed for 12 to 105 months. One patient, who had a right pelvic sidewall recurrence 5 months following surgery, was treated with radiation therapy and is clinically without evidence of disease at 8 years. The patient with “glassy cell” carcinoma died of metastatic disease at 12 months. The remaining patients are living and well. In five patients, treatment was delayed 6 to 17 weeks RESULTS to improve fetal survival (Table 2). These patients were Patients’ ages ranged from 22 to 43 years, with an treated by cesarean section with radical hysterectomy average of 30.6 years. Average parity was 2.9 with a and pelvic lymphadenectomy. The post-treatment parange of 2 to 5. The diagnosis was made by cervical thology in the four patients diagnosed initially by coniconization in seven patients, by cervical biopsy in three, zation showed only focal residual disease or carcinoma and by removal of a cervical polyp in the remaining in situ. The patient with “glassy cell” carcinoma had a patient. Three patients were in the first trimester, and positive lymph node. She received postoperative radiaeight were in the second trimester of their pregnancy at tion therapy and subsequently recurred and died of metthe time of diagnosis. Five of those cases diagnosed astatic disease at 15 months. She received chemotherapy during the second trimester were allowed delays in treat- without any response. The remaining four patients have been followed for 13 to 35 months with no evidence of ment to improve fetal survival. Six patients were managed without delay by termi- disease. Three infants in the delayed group had uncomplicated nation of pregnancy and radical hysterectomy and pelvic neonatal courses. One infant had a lecithin-sphingomyelymphadenectomy (Table 1). In three of six patients dilin ratio (L/S) equal to 1.6 three days before delivery agnosed initially by conization, post-treatment pathology and developed mild respiratory distress. This infant redemonstrated that two had residual CIN III and one had quired 1 day of oxygen administration and spent 7 days no residual disease. Another patient had focal residual in the NICU (Table 2). adenocarcinoma. In retrospect, the pathology in these The two remaining infants had more complicated neofour patients was favorable for a delay in treatment had natal courses. The first was delivered at 28 weeks gesfetal survival been desired. The lymph nodes in all six tation and developed severe hyaline membrane disease, patients were negative for metastatic disease. requiring 36 days of mechanical ventilation and 57 days The six patients treated without delay have been fol-
hyaline membrane disease, bronchopulmonary dysplasia, and grades 3 and 4 intraventricular hemorrhage were calculated. The mean number of ventilator days, supplemental oxygen days, and total NICU days were determined for each group.
TABLE 1 Stage I-B Cervical Carcinoma in Pregnancy-Treated with Termination and Pelvic Lymphadenectomy
Case
Age
1 2 3
40 23 43
Cone-KC Cone-SCC Bx-SCC
4
41
5
23
Cone-multifocal see w/bwh involve. Bx-glassy cell cancer
6
28
Preop path
Bx-adenoca
GA at ds/surg
of Pregnancy and Radical Hysterectomy
DX-surg interval (weeks)
Postop path
Lymph nodes
Maternal outcome
15117 1st TM 8/10
2.5 5.0 2.0
CIN III No resid. Invasive SCC w/lymph. invasion
t-1 (-) t-1
16/18
2.0
Resid. focal CIS
C-1
NED-60 months NED-105 months WP radiation W/boost to sidewall. Recur. at 5 months. NED-100 months NED-15 months
13/14
1.5
C-1
DOD-12
months
8124
16
Typical glassy cell cancer Focal resid. adenoca
(-)
NED-98
months
Note. Abbreviations: SCC, squamous cell cancer; CIN, cervical intraepithelial neoplasia; NED, no evidence of disease; DOD, dead of disease.
STAGE I-B CERVICAL
63
CANCER DURING PREGNANCY
TABLE 2
StageI-B Cervical Carcinoma in Pregnancy-Delayed Treatment by C-Sectionand Radical Hysterectomyand Pelvic Lymphadenectomyfor Improved Fetal Survival GA at dx/surg
DX-surg delay (weeks)
Case
Age
1
22
Polyp-see
22/28
6
2
34
Cone-SCC
24/35
11
3
31
Cone-SCC
24134
10
4’
28
Cone-SCC
21135
5
31
Cone-extensive CIN III w/gland involv. and foci of SCC invasion
20131
Preop path
Note. Abbreviations: disease. ’ See text.
Lymph nodes
Fetal outcome
Typical glassy cell cancer
1+
890 g F Apgars 718 very complic. neonatal course”
Circumferential severe dysplasia to CIS and focal microinvasion CIN III all quads small focus susp. for microinvasion
t-1
14
Focal residual SCC w/h@ invasion
C-1
17
Multifocal CIS
t-1
1300 g M Apgars l/4 very complic. neonatal coursea 2800 g M Apgars 719 Min. complic. neonatal course” 3300 g M Apgars 9/9 uncomplicated neonatal course 3360gM Apgars 819 uncomplicated neonatal course
Postop path
-
C-1
Maternal outcome DOD. 15 months postsurg./XRT died w/widespread disease; no response to chemotherapy NED 35 months
NED 27 months
NED 26 months
NED 13 months
SCC, squamous cell cancer; CIN, cervical intraepithelial neoplasia; NED, no evidence of disease; DOD, dead of
of supplemental oxygen. In addition, she developed a jejunal perforation requiring a resection; a patent ductus arteriosis that required ligation; a grade 1 intraventricular hemorrhage; neonatal seizures; and stage 2 retrolental fibrosis during 102 days in the NICU. The other infant was delivered at 35 weeks, by dates, with an L/S ratio of 1.1 one week prior to delivery, which was not repeated. The Ballard examination demonstrated a 30- to 32-week gestation infant. He required 3 days of mechanical ventilation and 3 days of supplemental oxygen. A total of 24 days was spent in the NICU. These two infants illustrate neonatal complications that occur without an adequate delay for fetal maturity. The average delay between diagnosis and surgery for 60 nonpregnant women with stage I-B invasive cervical carcinoma treated at the University Hospital was 27.7 days with a range of 6 to 74 days. The rates of morbidity and mortality of 600 neonates delivered at University Hospital in 1984 and 1985 are listed in Table 3 and Fig. 1. Infants born at 26-27 weeks of gestation suffered a mortality rate of 32.8%. Of those born at 32-33 weeks, only 1.2% died. The principle risk
to the premature infant is the development of hyaline membrane disease (HMD) and the consequences related to the management of this condition. The risk of HMD decreased from 86.9% at 26-27 weeks to 12.7% at 3435 weeks. Over the same interval the rate of bronchopulmonary dysplasia (BPD) fell from 59 to 2.4%. The rate of complicated intraventricular hemorrhage (IVH) fell from 32.7 to 1.8%. The degree of morbidity assoTABLE 3 Mortality, Incidence of Hyaline Membrane(HMD), Bronchopulmonary Dysplasia (BPD), and Complicated Intraventricular Hemorrhage (IVH) of 600 NICU Infants by Completed Gestational weeks
24-25 26-27 28-29 30-31 32-33 34-35
weeks, weeks, weeks, weeks, weeks, weeks,
R n n n n n
= = = = = =
30 61 67 129 163 150
Mortality
HMD
BPD
IVH
66.7% 32.8% 20.9% 9.3% 1.2% 2.7%
93.3% 86.9% 71.6% 46.5% 33.7% 12.7%
50.0% 59.0% 34.3% 13.9% 2.4% 1.3%
36.7% 32.7% 34.2% 7.6% 1.8% 1.3%
64
GREER ET AL.
24-25
26-27
28-29
30-31
32-33
24-25
34-35
26-27
28-29
30-31
32-33
34-35
WEEKS COMPLETED GESTATION
COMPLETED WEEKS GESTATION 0 Morfallty OHM) .SPD . IVH
e VENT DAYS
D 02 DAYS
. NW
DAYS
FIG. 1. Mortality, incidence of hyaline membrane (HMD), bronchopulmonary dysplasia (BPD), and complicated intraventricular hemorrhage (IVH) of 600 NICU infants by completed gestational weeks.
FIG. 2. Ventilator dependent days, supplemental oxygen days (0,) and total NICU days of 600 NICU infants by completed gestational weeks.
ciated with HMD can be estimated by the support required (Table 4, Fig. 2). The mean length of mechanical ventilation and supplemental oxygen fell from 25.0 and 36.1 days at 26-27 weeks to 0.7 and 1.3 days at 34-35 weeks. The total length of hospitalization fell from 48.9 to 11.4 days. These data indicate that for every additional 2 weeks of intrauterine life, there is significant decrease in morbidity and mortality of the premature infant. The low mortality and morbidity at 34 to 35 weeks is a reflection of fetal maturity. Predelivery assessment of fetal lung maturity should further reduce neonatal morbidity and mortality.
Longer delays in more advanced disease for surgical staging has been practiced without evidence of progression of disease. Planned delays in treatment of up to 17 weeks in this small series of pregnant patients were not associated with any progression of disease. The final pathology was favorable in all but one of these patients, who had a “glassy cell” cancer. In addition, the final pathology was favorable for delay in four of the patients who had immediate treatment. The two patients that died of disease in this series had typical “glassy cell” carcinomas. The survival of patients with stage I-B “glassy cell” carcinoma diagnosed at the University Hospital is 50%. There was one patient with “glassy cell” carcinoma in each group of this series, The decision to treat or delay treatment of cervical carcinoma during pregnancy is not difficult if the pregnancy is unwanted prior to 24 weeks, if the cancer is diagnosed when fetal maturity has been attained, or if the cancer is far advanced and a delay will not change the maternal prognosis. The difficult decision arises when the pregnancy is wanted and the fetus is not mature. Parents need to participate in the decision-making process and need adequate information on which to base their decision. The NICU data clearly demonstrate a dramatic decrease in infant mortality and morbidity with increasing gestational age up to 36 weeks. If a decision is made to delay treatment, the delay should be long enough to achieve fetal lung maturity and avoid hyaline membrane disease. The data presented are only for the neonatal period. Equally important are long-term developmental sequelae of low birth weight infants. A 7-year longitudinal report of infants weighing less than 1500 g revealed deficits in IQ, visual-motor integration, and reading. In that study, 54% of the children required special education or resource help at age 7 [7]. Complicated intraventricular hemorrhage is associated with major neurological handicaps in childhood [8].
DISCUSSION The traditional recommendation for immediate treatment of the pregnant patient with cervical cancer has little scientific basis. Anecdotal reports claiming deleterious effects on maternal outcome are poorly documented [3,4]. Studies have demonstrated no difference in survival between pregnant and nonpregnant patients controlling for stage of disease [5,6]. The delay from diagnosis to surgical treatment in nonpregnant patients in this investigation averaged 4 weeks and has not caused undue concern. Until recently, a 6-week delay between cone biopsy and definitive surgery was advocated. TABLE
4
Ventilator DependentDays, SupplementalOxygenDays, and Total NICU Daysof 600NICU Infants by CompletedGestational Weeks
24-25 26-27 28-29 30-31 32-33 34-35
weeks, n = 30 weeks, n = 61 weeks, n = 67 weeks, n = 12 weeks, n = 163
weeks, n = 150
Vent days
0, Days
NICU days
27.8 25.0 15.1 4.5
43.0 36.1 26.6 9.7 4.0 1.3
45.4 48.9 45.0 25.9 17.2 11.4
1.5 0.7
STAGE I-B CERVICAL
CANCER DURING PREGNANCY
In summary, delays of treatment in select pregnant patients with early invasive cervical carcinoma can be offered to women who express a desire to maintain their pregnancy. There may be a small increased risk in maternal outcome. Consequently, to balance this risk, the required length of the delay should be clearly sufficient to achieve documented fetal lung maturity which will permit the delivery of an infant with reasonably low risk of morbidity and mortality. The optimal management would be combined management by a gynecologic oncologist and a perinatologist with availability of a NICU. REFERENCES 1. Shingleton, H., and Orr, J. W. Cancer complicating pregnancy, Cancer of the cervix: Diagnosis and treatment, in Current Reviews in Ob. Gyn, No. 5 in series. Churchill Livingston, 198-209 (1983).
65
2. Ballard, J. L., Novak, K. K., and Driver, M. A simplified score for assessment of fetal maturation of newly born infants, J. Pediurr. 95, 769-784 (1979). 3. Fay, R. A. Cervical carcinoma associated with pregnancy, Lancer 2, 1213 (1982). 4. Todd, 0. E. Cancer of the cervix, J. Mich. State Med. Sot., 1911% (March, 1941). 5. Creasman, W. T., Rutledge, F. N., and Fletcher, G. H. Carcinoma of the cervix associated with pregnancy, Ob. Gyn. 36, 495-501 (1970). 6. Lee, R. B., Neglia, W., and Park, R. C. Cervical carcinoma in pregnancy, Ob. Gyn. 58, 584-589 (1981). 7. Vohr, B. R., and Coil, C. T. G. Neurodevelopmental and school performance of very low-birth-weight infants: A seven-year longitudinal study, Pediatrics 76, 345-350 (1985). 8. Papile, L. A., Munsik-Bruno, G., and Schaefer, A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J. Pediatr. 103, 273-277 (1983).
ONCOLOGY
34,
61-65 (1989)
Fetal and Maternal Considerations in the Management of Stage I-B Cervical Cancer during Pregnancy’ B. E. GREER, M.D.,’ T. R. EASTERLING, M.D., D. A. MCLENNAN, M.D., T. J. BENEDETTI, M.D., J. M. CAIN, M.D., D. C. FIGGE, M.D., H. K. TAMIMI, M.D., AND J. C. JACKSON, M.D.* University of Washington, Departments of Obstetrics and Gynecology, and *Pediatrics, Seattle, Washington, 98195 Received March 1, 1988
The timing of treatment for stage I-B cervical carcmoma diagnosed during pregnancy is complicated by conflicting concerns for fetal survival and control of malignancy. There were 11 pregnant women with stage I-B cervical carcinoma diagnosed prior to fetal viability since 1969. Six patients were managed with termination of pregnancy and radical hysterectomy with pelvic lymphadenectomy. In 5 patients, treatment was delayed for 6 to 17 weeks and then delivery was accomplished by cesareansection followed directly by radical hysterectomy and pelvic lymphadenectomy. Two of the infants experienced complicated neonatal courses and would have benefited from additional delay. Benefits that could be achieved by delaying delivery for the fetus were calculated from a review of 600 inborn infants without congenital anomalies admitted to the neonatal intensive care (NICU) during 1984 and 1985. Neonatal mortality decreasedfrom 32.8% at 2627 weeks to 2.7% at 34-35 weeks gestation. Similar improvements in neonatal morbidity were demonstrated. Although adverse maternal outcomes were not associated with delay, an evaluation of risk cannot be derived from this series. Significant fetal benefit can accrue from relatively short delays in planned delivery dates. When stage I-B cervical carcinoma is diagnosed during pregnancy and when fetal survival is desired, delivery should be delayed to achieve fetal maturity, rather than only potential viability. o 1989 Academic
Ress, Inc.
INTRODUCTION Carcinoma of the cervix associated with an intrauterine pregnancy is an uncommon problem. Between 0.02 and 0.4% of pregnancies are complicated by invasive cervical cancer [ 11. Historically, immediate treatment was recommended without regard to the pregnancy. More recently, arbitrary time limits of “fetal viability” have been used without consideration of fetal mortality ’ Presented at the Annual Meeting of The Western Association of Gynecologic Oncologists, May 13-16, 1987. ’ To whom reprint requests for reprints should he addressed.
and morbidity. Highly complex ethical issues, religious beliefs, and emotional considerations for the patient and family are superimposed on this medical dilemma. Both the maternal and the fetal outcomes should be considered when counseling the pregnant patient with invasive cervical cancer. This report attempts to address these issues and offer guidelines for management of both stage I-B cervical carcinoma and pregnancy, when they coexist. MATERIALS
AND METHODS
Between January 1969 and February 1986, at the University of Washington, 11 pregnant patients were treated on the Gynecologic Oncology Service for stage I-B cervical carcinoma. Age, gravidity, parity, methods of diagnosis and treatment, pathology, and maternal and fetal outcomes were considered. To determine the customary interval between diagnosis and definitive therapy at this institution, the records of all patients with stage I-B cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy during 1983 and 1984 were reviewed. None of these patients was pregnant. Expected neonatal mortality and morbidity in premature infants were determined by abstracting data from the University of Washington Neonatal Intensive Care Unit (NICU) database. Six hundred consecutive NICU admissions
since January
1, 1984, representing
inborn
infants without congenital anomalies and with gestational ages between 24 and 35 weeks, were evaluated. Data were grouped by 2-week gestational age spans. Gestational age was determined by the Ballard method [2] and obstetrical parameters. Stillborn infants and those infants that could not be resuscitated in the delivery room were excluded. The incidence of neonatal death prior to discharge, 61 lM9i-h8258189
$1.50
Copyright 0 1989by AcademicPress,Inc. All rights of reproductionin any form reserved.
62
GREER ET AL.
lowed for 12 to 105 months. One patient, who had a right pelvic sidewall recurrence 5 months following surgery, was treated with radiation therapy and is clinically without evidence of disease at 8 years. The patient with “glassy cell” carcinoma died of metastatic disease at 12 months. The remaining patients are living and well. In five patients, treatment was delayed 6 to 17 weeks RESULTS to improve fetal survival (Table 2). These patients were Patients’ ages ranged from 22 to 43 years, with an treated by cesarean section with radical hysterectomy average of 30.6 years. Average parity was 2.9 with a and pelvic lymphadenectomy. The post-treatment parange of 2 to 5. The diagnosis was made by cervical thology in the four patients diagnosed initially by coniconization in seven patients, by cervical biopsy in three, zation showed only focal residual disease or carcinoma and by removal of a cervical polyp in the remaining in situ. The patient with “glassy cell” carcinoma had a patient. Three patients were in the first trimester, and positive lymph node. She received postoperative radiaeight were in the second trimester of their pregnancy at tion therapy and subsequently recurred and died of metthe time of diagnosis. Five of those cases diagnosed astatic disease at 15 months. She received chemotherapy during the second trimester were allowed delays in treat- without any response. The remaining four patients have been followed for 13 to 35 months with no evidence of ment to improve fetal survival. Six patients were managed without delay by termi- disease. Three infants in the delayed group had uncomplicated nation of pregnancy and radical hysterectomy and pelvic neonatal courses. One infant had a lecithin-sphingomyelymphadenectomy (Table 1). In three of six patients dilin ratio (L/S) equal to 1.6 three days before delivery agnosed initially by conization, post-treatment pathology and developed mild respiratory distress. This infant redemonstrated that two had residual CIN III and one had quired 1 day of oxygen administration and spent 7 days no residual disease. Another patient had focal residual in the NICU (Table 2). adenocarcinoma. In retrospect, the pathology in these The two remaining infants had more complicated neofour patients was favorable for a delay in treatment had natal courses. The first was delivered at 28 weeks gesfetal survival been desired. The lymph nodes in all six tation and developed severe hyaline membrane disease, patients were negative for metastatic disease. requiring 36 days of mechanical ventilation and 57 days The six patients treated without delay have been fol-
hyaline membrane disease, bronchopulmonary dysplasia, and grades 3 and 4 intraventricular hemorrhage were calculated. The mean number of ventilator days, supplemental oxygen days, and total NICU days were determined for each group.
TABLE 1 Stage I-B Cervical Carcinoma in Pregnancy-Treated with Termination and Pelvic Lymphadenectomy
Case
Age
1 2 3
40 23 43
Cone-KC Cone-SCC Bx-SCC
4
41
5
23
Cone-multifocal see w/bwh involve. Bx-glassy cell cancer
6
28
Preop path
Bx-adenoca
GA at ds/surg
of Pregnancy and Radical Hysterectomy
DX-surg interval (weeks)
Postop path
Lymph nodes
Maternal outcome
15117 1st TM 8/10
2.5 5.0 2.0
CIN III No resid. Invasive SCC w/lymph. invasion
t-1 (-) t-1
16/18
2.0
Resid. focal CIS
C-1
NED-60 months NED-105 months WP radiation W/boost to sidewall. Recur. at 5 months. NED-100 months NED-15 months
13/14
1.5
C-1
DOD-12
months
8124
16
Typical glassy cell cancer Focal resid. adenoca
(-)
NED-98
months
Note. Abbreviations: SCC, squamous cell cancer; CIN, cervical intraepithelial neoplasia; NED, no evidence of disease; DOD, dead of disease.
STAGE I-B CERVICAL
63
CANCER DURING PREGNANCY
TABLE 2
StageI-B Cervical Carcinoma in Pregnancy-Delayed Treatment by C-Sectionand Radical Hysterectomyand Pelvic Lymphadenectomyfor Improved Fetal Survival GA at dx/surg
DX-surg delay (weeks)
Case
Age
1
22
Polyp-see
22/28
6
2
34
Cone-SCC
24/35
11
3
31
Cone-SCC
24134
10
4’
28
Cone-SCC
21135
5
31
Cone-extensive CIN III w/gland involv. and foci of SCC invasion
20131
Preop path
Note. Abbreviations: disease. ’ See text.
Lymph nodes
Fetal outcome
Typical glassy cell cancer
1+
890 g F Apgars 718 very complic. neonatal course”
Circumferential severe dysplasia to CIS and focal microinvasion CIN III all quads small focus susp. for microinvasion
t-1
14
Focal residual SCC w/h@ invasion
C-1
17
Multifocal CIS
t-1
1300 g M Apgars l/4 very complic. neonatal coursea 2800 g M Apgars 719 Min. complic. neonatal course” 3300 g M Apgars 9/9 uncomplicated neonatal course 3360gM Apgars 819 uncomplicated neonatal course
Postop path
-
C-1
Maternal outcome DOD. 15 months postsurg./XRT died w/widespread disease; no response to chemotherapy NED 35 months
NED 27 months
NED 26 months
NED 13 months
SCC, squamous cell cancer; CIN, cervical intraepithelial neoplasia; NED, no evidence of disease; DOD, dead of
of supplemental oxygen. In addition, she developed a jejunal perforation requiring a resection; a patent ductus arteriosis that required ligation; a grade 1 intraventricular hemorrhage; neonatal seizures; and stage 2 retrolental fibrosis during 102 days in the NICU. The other infant was delivered at 35 weeks, by dates, with an L/S ratio of 1.1 one week prior to delivery, which was not repeated. The Ballard examination demonstrated a 30- to 32-week gestation infant. He required 3 days of mechanical ventilation and 3 days of supplemental oxygen. A total of 24 days was spent in the NICU. These two infants illustrate neonatal complications that occur without an adequate delay for fetal maturity. The average delay between diagnosis and surgery for 60 nonpregnant women with stage I-B invasive cervical carcinoma treated at the University Hospital was 27.7 days with a range of 6 to 74 days. The rates of morbidity and mortality of 600 neonates delivered at University Hospital in 1984 and 1985 are listed in Table 3 and Fig. 1. Infants born at 26-27 weeks of gestation suffered a mortality rate of 32.8%. Of those born at 32-33 weeks, only 1.2% died. The principle risk
to the premature infant is the development of hyaline membrane disease (HMD) and the consequences related to the management of this condition. The risk of HMD decreased from 86.9% at 26-27 weeks to 12.7% at 3435 weeks. Over the same interval the rate of bronchopulmonary dysplasia (BPD) fell from 59 to 2.4%. The rate of complicated intraventricular hemorrhage (IVH) fell from 32.7 to 1.8%. The degree of morbidity assoTABLE 3 Mortality, Incidence of Hyaline Membrane(HMD), Bronchopulmonary Dysplasia (BPD), and Complicated Intraventricular Hemorrhage (IVH) of 600 NICU Infants by Completed Gestational weeks
24-25 26-27 28-29 30-31 32-33 34-35
weeks, weeks, weeks, weeks, weeks, weeks,
R n n n n n
= = = = = =
30 61 67 129 163 150
Mortality
HMD
BPD
IVH
66.7% 32.8% 20.9% 9.3% 1.2% 2.7%
93.3% 86.9% 71.6% 46.5% 33.7% 12.7%
50.0% 59.0% 34.3% 13.9% 2.4% 1.3%
36.7% 32.7% 34.2% 7.6% 1.8% 1.3%
64
GREER ET AL.
24-25
26-27
28-29
30-31
32-33
24-25
34-35
26-27
28-29
30-31
32-33
34-35
WEEKS COMPLETED GESTATION
COMPLETED WEEKS GESTATION 0 Morfallty OHM) .SPD . IVH
e VENT DAYS
D 02 DAYS
. NW
DAYS
FIG. 1. Mortality, incidence of hyaline membrane (HMD), bronchopulmonary dysplasia (BPD), and complicated intraventricular hemorrhage (IVH) of 600 NICU infants by completed gestational weeks.
FIG. 2. Ventilator dependent days, supplemental oxygen days (0,) and total NICU days of 600 NICU infants by completed gestational weeks.
ciated with HMD can be estimated by the support required (Table 4, Fig. 2). The mean length of mechanical ventilation and supplemental oxygen fell from 25.0 and 36.1 days at 26-27 weeks to 0.7 and 1.3 days at 34-35 weeks. The total length of hospitalization fell from 48.9 to 11.4 days. These data indicate that for every additional 2 weeks of intrauterine life, there is significant decrease in morbidity and mortality of the premature infant. The low mortality and morbidity at 34 to 35 weeks is a reflection of fetal maturity. Predelivery assessment of fetal lung maturity should further reduce neonatal morbidity and mortality.
Longer delays in more advanced disease for surgical staging has been practiced without evidence of progression of disease. Planned delays in treatment of up to 17 weeks in this small series of pregnant patients were not associated with any progression of disease. The final pathology was favorable in all but one of these patients, who had a “glassy cell” cancer. In addition, the final pathology was favorable for delay in four of the patients who had immediate treatment. The two patients that died of disease in this series had typical “glassy cell” carcinomas. The survival of patients with stage I-B “glassy cell” carcinoma diagnosed at the University Hospital is 50%. There was one patient with “glassy cell” carcinoma in each group of this series, The decision to treat or delay treatment of cervical carcinoma during pregnancy is not difficult if the pregnancy is unwanted prior to 24 weeks, if the cancer is diagnosed when fetal maturity has been attained, or if the cancer is far advanced and a delay will not change the maternal prognosis. The difficult decision arises when the pregnancy is wanted and the fetus is not mature. Parents need to participate in the decision-making process and need adequate information on which to base their decision. The NICU data clearly demonstrate a dramatic decrease in infant mortality and morbidity with increasing gestational age up to 36 weeks. If a decision is made to delay treatment, the delay should be long enough to achieve fetal lung maturity and avoid hyaline membrane disease. The data presented are only for the neonatal period. Equally important are long-term developmental sequelae of low birth weight infants. A 7-year longitudinal report of infants weighing less than 1500 g revealed deficits in IQ, visual-motor integration, and reading. In that study, 54% of the children required special education or resource help at age 7 [7]. Complicated intraventricular hemorrhage is associated with major neurological handicaps in childhood [8].
DISCUSSION The traditional recommendation for immediate treatment of the pregnant patient with cervical cancer has little scientific basis. Anecdotal reports claiming deleterious effects on maternal outcome are poorly documented [3,4]. Studies have demonstrated no difference in survival between pregnant and nonpregnant patients controlling for stage of disease [5,6]. The delay from diagnosis to surgical treatment in nonpregnant patients in this investigation averaged 4 weeks and has not caused undue concern. Until recently, a 6-week delay between cone biopsy and definitive surgery was advocated. TABLE
4
Ventilator DependentDays, SupplementalOxygenDays, and Total NICU Daysof 600NICU Infants by CompletedGestational Weeks
24-25 26-27 28-29 30-31 32-33 34-35
weeks, n = 30 weeks, n = 61 weeks, n = 67 weeks, n = 12 weeks, n = 163
weeks, n = 150
Vent days
0, Days
NICU days
27.8 25.0 15.1 4.5
43.0 36.1 26.6 9.7 4.0 1.3
45.4 48.9 45.0 25.9 17.2 11.4
1.5 0.7
STAGE I-B CERVICAL
CANCER DURING PREGNANCY
In summary, delays of treatment in select pregnant patients with early invasive cervical carcinoma can be offered to women who express a desire to maintain their pregnancy. There may be a small increased risk in maternal outcome. Consequently, to balance this risk, the required length of the delay should be clearly sufficient to achieve documented fetal lung maturity which will permit the delivery of an infant with reasonably low risk of morbidity and mortality. The optimal management would be combined management by a gynecologic oncologist and a perinatologist with availability of a NICU. REFERENCES 1. Shingleton, H., and Orr, J. W. Cancer complicating pregnancy, Cancer of the cervix: Diagnosis and treatment, in Current Reviews in Ob. Gyn, No. 5 in series. Churchill Livingston, 198-209 (1983).
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2. Ballard, J. L., Novak, K. K., and Driver, M. A simplified score for assessment of fetal maturation of newly born infants, J. Pediurr. 95, 769-784 (1979). 3. Fay, R. A. Cervical carcinoma associated with pregnancy, Lancer 2, 1213 (1982). 4. Todd, 0. E. Cancer of the cervix, J. Mich. State Med. Sot., 1911% (March, 1941). 5. Creasman, W. T., Rutledge, F. N., and Fletcher, G. H. Carcinoma of the cervix associated with pregnancy, Ob. Gyn. 36, 495-501 (1970). 6. Lee, R. B., Neglia, W., and Park, R. C. Cervical carcinoma in pregnancy, Ob. Gyn. 58, 584-589 (1981). 7. Vohr, B. R., and Coil, C. T. G. Neurodevelopmental and school performance of very low-birth-weight infants: A seven-year longitudinal study, Pediatrics 76, 345-350 (1985). 8. Papile, L. A., Munsik-Bruno, G., and Schaefer, A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J. Pediatr. 103, 273-277 (1983).