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Carcinoma of the cervix and pregnancy
GYNECOLOGIC
ONCOLOGY
Carcinoma
1,283-289
(1973)
of the
Cervix
and
Pregnancy’
RONALD C. DUDAN, M.D.,2 JOSEPH L. YON, JR., M.D., JOHN H. FORD, JR., M.D. AND HERVY E. AVERETTE, M.D. Gynecologic Oncology Seruice, Department University of Miami School of Medicine, Receioed
August
of Obstetrics Miami,
and Florida
Gynecology, 33152
13,1973
All patients with cervical cancer diagnosed during pregnancy at Jackson Memorial Hospital, the University of Miami School of Medicine, from 1960-1970 have been reviewed. There are 122 patients in this group; 99 had carcinoma in situ and 23 had invasive cancer. The prevalence rate for carcinoma in situ during pregnancy, was 0.192% and for invasive carcinoma, 0.046%. Of the patients, 95% had a Class III or higher Papanicolaou smear which led to the diagnosis. This is a young population in that the mean age was 29.6 years. Therapy for Stage 0 carcinoma and Stage IA (microinvasive) carcinoma was total hysterectomy, whereas radical hysterectomy with pelvic lymphadenectomy was recommended for Stage IB/IIAcarcinoma of the cervix. Radiotherapy was utilized for more advanced disease or in patients with contraindications to surgery. The importance of adequate follow-up is emphasized in that six patients with carcinoma in situ during pregnancy were found to have invasive carcinoma at a later date and two patients with invasive carcinoma had progression of their disease when treatment was delayed. The survival rate with radical operation during pregnancy for Stage IB and HA carcinoma has been 90% in 10 patients followed nearly 3 years or longer. An additional four patients had radical operation in the follow-up period and all four are clinically free of recurrent cancer at the present time. Major complications were high in those patients treated with primary radiotherapy, and of the five patients who were so treated, four have died, one with recurrent carcinoma and the other three from complications of radiotherapy. An additional three patients were treated with primary radiotherapy during the intrapartum period. In this group two have died of recurrent cancer while one remains clinically free of cancer.
Cervical cancer presents as an uncommon concurrent disease in pregnancy. The incidence of cervical carcinoma in pregnancy varies from 1 in 2000 to 1 in 6000 pregnancies [l-7]. Carcinoma in situ has been reported to occur as frequently as 0.49% in pregnancy [4]. At Jackson Memorial Hospital, University of Miami School of Medicine we have observed a relatively high incidence of cervical carcinoma among our pregnant patients. Several interesting factors related to disease during various periods of observation prompted a review of our experience. ’ The opinions expressed herein represent those of the authors and are not necessarily the Bureau of Medicine and Surgery, or the U. S. Navy as a whole. p Advanced Clinical Fellow, American Cancer Society. Present address: Department trics and Gynecology, Naval Hospital, Key West, Florida. ” U. S. Navy-sponsored Fellow, Gynecologic Oncology. Copyright All rights
@ 1973 by Academic Press, Inc. of reproduction in any form reserved.
283
those of Obste-
of
284
DUDAN
MATERIALS
ET
AL.
AND
METHODS
During the 11-year period from 1960 through 1970 the Department of Obstetrics and Gynecology, University of Miami School of Medicine has diagnosed and managed 122 patients with carcinoma of the cervix associated with pregnancy. Only those patients with a diagnosis of either in situ or invasive carcinoma during pregnancy are included. Patients who had carcinoma discovered during the early postpartum period are excluded from this study. Of the 122 patients, 99 were diagnosed as having carcinoma in situ and 23 had invasive carcinoma. Thus, the incidence of cervical carcinoma in pregnancy at our institution in 122 per 52,500 deliveries or 0.238%. For in situ carcinoma, it is 99 per 52,500 deliveries (0.192%), and for invasive carcinoma it is 23 per 52,500 deliveries (0.046%). The diagnosis of cancer in pregnancy at this institution is usually made as a result of routine cytologic screening in the prenatal clinics. Ninety-five percent of our patients were referred because of abnormal cytology. Five percent had symptoms of vaginal bleeding which ultimately led to the diagnosis of carcinoma. This experience would reemphasize the importance of early prenatal care, routine cytologic screening in all pregnant patients, and through evaluation of all patients with vaginal bleeding. Women with suspicious or positive cytology during pregnancy receive the same diagnostic workup as the nonpregnant patient. Punch biopsies of any suspicious lesion or area that fails to take a Schiller stain are performed. If the punch biopsy fails to show invasive carcinoma, cold knife cone biopsy is performed. Our experience with cone biopsy during pregnancy has been reported earlier [Sl. During the time covered by this study colposcopy was not available in our clinic. Currently all patients with atypical, suspicious, or positive cytology are colposcoped and selective biopsies performed in an attempt to reduce the number of cone biopsies necessary.
AGE Age (years)
OF PATIENTS Stage
0
WITH Stage
TABLE CERVICAL IA”
I NEOPLASIA Stage
IB
Stage
1
-
17-19 20-24 25-29 30-34 35-40 40-44
4 23 38 20 8 6
Total
99
6
15
Mean age (year) 29.6
29.0
30.0
31.9
’ For the purposes of stromal invasion.
of this
1 2 2
4 7 2 1
1
report,
Stage
IN PREGNANCY
IA is limited
to those
IIB
Stage
IIIB
1 1
cases
showing
1
less than
1 mm
CARCINOMA
OF
CERVIX
AND
285
PREGNANCY
The patient age range was from 17 to 44 years with a mean age of 29.6 years. There were 47 Caucasians and 75 Negroes. Parity ranged from 0 to 12 with a mean parity of 4. Table I is an analysis of the age distribution of our patients with cervical cancer during pregnancy. The mean age of patients with in situ carcinoma is 29 years and for Stage IA and IB carcinoma is 30.9 years. It is of interest that the mean age of patients with early invasive cancer is essentially the same as those with in situ carcinoma. Of our patients, 17% were found to have carcinoma of the cervix in the first trimester, 30% in the second trimester, and 53% in the third trimester. Our general plan of management for patients with carcinoma in situ is to allow the pregnancy to proceed to term and allow vaginal delivery. Definitive therapy for the carcinoma in situ is either abdominal or vaginal hysterectomy approximately 12 weeks postpartum depending on the patient’s age, parity, desire for further pregnancy, and follow-up cytologic examinations. Stage IA less than 1 mm stromal invasion, is treated by cesarean section extrafascial hysterectomy at term. Stage IB and IIA carcinoma are usually treated by radical hysterectomy and bilateral pelvic lymphadenectomy. Radiotherapy is utilized for more advanced invasive disease or for patients who have medical contraindications or refuse radical operation. RESULTS Carcinoma
in Situ
During the period of this review, 21 abdominal hysterectomies and 30 vaginal hysterectomies were performed for carcinoma in situ. Of these, three abdominal hysterectomies were performed in the immediate postpartum period and four cesarean section hysterectomies were performed in “highrisk” patients. We define our high-risk patient as one who by past medical records will return to the clinics or hospital only for emergency care or for prenatal care late in her pregnancy. One abdominal hysterectomy was performed in early pregnancy for therapeutic abortion, the carcinoma in situ being incidental and one cesarean hysterectomy was performed upon a paTABLE II ADVANCEMENT OF DISEASE IN FOLLOW-UP OF CERVICAL CANCER DIAGNOSED DURING PREGNANCY Patient 1. 2. 3. 4. 5. 6. 7. 8.
L.P. J.H. G.C. F.H. S.B. M.H. R.W. M.E. * P.G. = Pregnancy.
Stage
P.G.” 0 0 0 0 0 0 IB IB
Stage
Following IA IB IB IB IB IIA IIA IIIB
P.G.
Time 2 2 5 1 5 6 2 6
interval months months months year years years months months
286
DUDAN
ET
AL.
tient undergoing elective repeat cesarean section. Of those patients treated, 32 (63%) had residual carcinoma in situ in the surgical specimen while 19 (37%) had the disease removed by the cone biopsy. Six patients with a diagnosis of in situ carcinoma during pregnancy were found to have more advanced disease at a later date (Table II). Patients 1 and 2 were found to have persistent positive cytology in the postpartum period and repeat diagnostic workup revealed Stage IA and Stage IB carcinoma, respectively. Patients 3,4, 5, and 6 had a delay interval of from 5 months to 6 years after delivery which was directly related to patient delay and refusal of follow-up examinations. Therefore, of the 99 patients diagnosed as having in situ carcinoma during pregnancy, 51 have had definitive therapy, six had more advanced disease in an interval from 2 months to 6 years after delivery, and 42 patients are under continued observation. Invasive
Carcinoma
Six patients were found to have Stage IA cervical carcinoma (less than 1 mm stromal invasion). Five of the six were treated by cesarean section extrafascial hysterectomy at term and the other patient had an abdominal hysterectomy after a cone biopsy in early pregnancy when bleeding could not be controlled by more conservative measures. To date this management has been successful since all patients remain free of disease at the time of this report. Seventeen patients had a diagnosis of frankly invasive cervical carcinoma during pregnancy. In this group four patients underwent cesarean section radical hysterectomy at or near term, two patients had a hysterotomy and radical hysterectomy in the second trimester, two patients had radical hysterectomy in the first trimester, and two patients had a radical hysterectomy in the immediate postpartum period when the diagnosis of invasive cancer was made at the time of delivery. Five patients were treated with primary radiotherapy during pregnancy and two patients refused any form of therapy at the time of initial diagnosis. In the radical hysterectomy group the operating time has ranged from 4 to 6 hr 30 min with an average operating time of 5 hr 11 min. Blood loss ranged from 1500 to 6000 cc with an average of 2835 cc. The postoperative hospital stay ranged from 11 to 22 days with an average stay of 15.5 days. There were three postoperative complications in this group. Two patients had superficial wond infections and one patient had a suspected but unconfirmed pulmonary embolus. In long-term follow-up one patient developed serum hepatitis, but recovered completely. No patient undergoing radical hysterectomy has developed a major complication such as ureterovaginal fistula, vesicovaginal fistula, or bowel obstruction. Two patients were found to have metastatic tumor to the pelvic lymph nodes and received postoperative radiotherapy to the pelvis as suggested by Guttmann [9] and Kelso [lo]. Of these two patients, one has died of diffuse metastatic carcinoma. The recurrent tumor was diagnosed within 13 years and the patient died within 2+ years after primary therapy, This time interval for recurrent disease is consistent with our observations in patients
CARCINOMA
OF
CERVIX
AND
PREGNANCY
287
having radical hysterectomy in the nonpregnant state. At the time of this writing all patients have been followed for nearly 3 years and 9 of the 10 radical hysterectomy patients have no evidence of recurrent disease. Five patients have been treated with primary radiotherapy during pregnancy. Of the five patients treated, three were clinical Stage IB, 1 was Stage IIB, and 1 was Stage IIIB. In this group four patients have died. One patient died of recurrent carcinoma. The other three deaths were due to complications of radiotherapy which include hemorrhage secondary to necrosis and rupture of the hypogastric artery, hemorrhage secondary to radiation changes in the bladder and rectum, and the third involving multiple small-bowel fistulas. The surviving patient had multiple complications of rectovaginal and vesicovaginal fistulas which required colostomy and urinary diversion, but is alive 9 years after primary therapy. Postpartum-Zntrapartum
Period
As noted in Table II eight patients with progression of disease were treated in the postpartum-intrapartum period. Six patients had a diagnosis of Stage 0 carcinoma during pregnancy, but were found to have more advanced disease in a follow-up period varying from 2 months to 6 years. Two patients had a diagnosis of Stage IB invasive carcinoma during pregnancy, but refused any form of initial therapy. Patient 1 was found to have Stage IA carcinoma, and abdominal hysterectomy was performed. She currently is clinically free of recurrent disease. Patients 2, 3, 4, and 5 were found to have Stage IB carcinoma in an interval of from 2 months to 5 years after delivery. These patients were treated by radical hysterectomy and bilateral pelvic lymphadenectomy. All four patients were free of metastatic disease to the pelvic lymph nodes and clinically remain free of disease in a follow-up period of at least 3 years. The remaining three patients were treated with radiotherapy, two for Stage IIA and one for Stage IIIB carcinoma. In this group two patients have died of recurrent or persistent disease while one patient is free of disease in a followup period of over 3 years. DISCUSSION Preliminary to any discussion of clinical experience at Jackson Memorial Hospital one must understand the usual patient we encounter. Most patients are from low socioeconomic groups including many migrant laborers. Medical care is sought only on an emergency basis or in late pregnancy. We believe this reflects in the fact that only 17% of our patients had a diagnosis of cancer made during the first trimester while 53% were diagnosed in the third trimester. Further difficulty is encountered in obtaining optimal follow-up or instituting primary therapy as evidence by the number of Stage 0 carcinoma patients who have not had definitive therapy and the two patients with early invasive carcinoma who refused therapy until the disease was more advanced. For these and other reasons that will be pointed out, our institution plans a more aggressive approach to the gravid patient with in situ carcinoma of the cervix.
288
DUDAN
ET
AL.
In the future we plan to use cesarean hysterectomy or postpartum hysterectomy for patients with Stage 0 carcinoma of the cervix, unless there is absolute patient reliability for follow-up care. We believe this is justified for the following reasons: (1) Most patients are of relatively high parity. (2) Many patients will not return for follow-up care. (3) Some patients will experience progression of disease as outlined in Table 2. (4) Of those hysterectomies performed for Stage 0 cancer, 63% had residual carcinoma in the surgical specimen. This probably indicates that a cone biopsy performed during pregnancy is not as extensive as a cone biopsy in the nonpregnant patient. 5. There have been no postoperative deaths in patients treated in this manner although we may expect some increased postoperative morbidity when compared to the hysterectomy performed at 12 weeks postpartum . We will continue to treat Stage IA (microinvasive) carcinoma by cesarean hysterectomy. Our results with radical hysterectomy for Stage IB-IIA carcinoma would seem to justify the procedure although the total number of patients treated in this manner is small. The major differences in measurable parameters in comparing the radical hysterectomy in the pregnant patient to our nonpregnant patient is an increase in total operating time and increased blood loss at operation. The absence of major complications, such as ureterovaginal fistula, vesicovaginal fistula, or bowel obstruction, combined with an apparent high survival rate would further justify this approach. We feel it is impossible to compare patients that have had radical operation to those who receive radiotherapy. A degree of patient selection always exists and those patients treated with radiotherapy have the benefit of clinical staging only while operative candidates have their stage of disease confirmed by preliminary abdominal and pelvic exploration. In this series the major complications secondary to radiation therapy have been very high and the survival rate has been very low. The radiation dosimitry used was in the levels recommended by other institutions, however, our results were not as favorable [ll]. We have no explanation for our poor results with radiotherapy,
REFERENCES 1. HAYDEN, C. E. Carcinoma of the 71, 780 (1956). 2. KISTNER, K. W., CORBACH, A. Gynecol. 9,554 (1957). 3. MCDUFF, A. C., CARNEY, W. I., O&et. Gynecol. 8, 196 (1965). 4. MAKSH, M., AND FITZGERALD, nancy. Cancer 9, 1195 (1956).
cervix C., AND
associated SSIITH,
AND WATERMAN, P. J. Carcinoma
with
pregnancy.
V. Cervical G. W. Cancer
Amer.
cancer
/. Obstet.
Cynecol.
in pregnancy.
Obstet.
of the cervix
in situ of the human
uterine
and pregnancy. cervix
in preg-
CARCINOMA
OF
CERVIX
AND
PREGNANCY
289
5. SADUGOR, W. G., PALMER, J. P., AND REINHARD, M. C. Carcinoma of the cervix concomitant with pregnancy. Amer. I. Obstet. Gynecol. 57,933 (1949). 6. STANDER, R. W., AND LEWIS, I. N. Carcinoma of the cervix and pregnancy. Amer. J. Obstet. Gynecol. 79, 164 (1960). 7. OSBAND, R., AND JONES, W. N. Carcinoma in situ in pregnancy. Amer. J. Obstet. Gynecol. 83, 599 ( 1962). 8. AVERETTE, H. E., NASSER, N., YANKOW, S. L., AND LITTLE, W. A. Cervical conization in pregnancy. Amer. J. Obstet. Gynecol. 106,543 (1970). 9. GUTTMANN, R. Significance of postoperative irradiation in carcinoma of the cervix; A ten year survey. Amer. J. Roentgenol. Radium Ther. Nucl. Med. 102 (1970). 10. KELSO, J. W., AND FUNNELL, J, W. Radical Wertheim hysterectomy.Amer. J. Obstet. Gynecol. 99, 106 (1967). 11. CREASMAN, W. T., RUTLEDGE, F. D., AND FLETCHER, G. H. Carcinoma of the cervix associated with pregnancy. Obstet. Gynecol. 36,495 (1970).
ONCOLOGY
Carcinoma
1,283-289
(1973)
of the
Cervix
and
Pregnancy’
RONALD C. DUDAN, M.D.,2 JOSEPH L. YON, JR., M.D., JOHN H. FORD, JR., M.D. AND HERVY E. AVERETTE, M.D. Gynecologic Oncology Seruice, Department University of Miami School of Medicine, Receioed
August
of Obstetrics Miami,
and Florida
Gynecology, 33152
13,1973
All patients with cervical cancer diagnosed during pregnancy at Jackson Memorial Hospital, the University of Miami School of Medicine, from 1960-1970 have been reviewed. There are 122 patients in this group; 99 had carcinoma in situ and 23 had invasive cancer. The prevalence rate for carcinoma in situ during pregnancy, was 0.192% and for invasive carcinoma, 0.046%. Of the patients, 95% had a Class III or higher Papanicolaou smear which led to the diagnosis. This is a young population in that the mean age was 29.6 years. Therapy for Stage 0 carcinoma and Stage IA (microinvasive) carcinoma was total hysterectomy, whereas radical hysterectomy with pelvic lymphadenectomy was recommended for Stage IB/IIAcarcinoma of the cervix. Radiotherapy was utilized for more advanced disease or in patients with contraindications to surgery. The importance of adequate follow-up is emphasized in that six patients with carcinoma in situ during pregnancy were found to have invasive carcinoma at a later date and two patients with invasive carcinoma had progression of their disease when treatment was delayed. The survival rate with radical operation during pregnancy for Stage IB and HA carcinoma has been 90% in 10 patients followed nearly 3 years or longer. An additional four patients had radical operation in the follow-up period and all four are clinically free of recurrent cancer at the present time. Major complications were high in those patients treated with primary radiotherapy, and of the five patients who were so treated, four have died, one with recurrent carcinoma and the other three from complications of radiotherapy. An additional three patients were treated with primary radiotherapy during the intrapartum period. In this group two have died of recurrent cancer while one remains clinically free of cancer.
Cervical cancer presents as an uncommon concurrent disease in pregnancy. The incidence of cervical carcinoma in pregnancy varies from 1 in 2000 to 1 in 6000 pregnancies [l-7]. Carcinoma in situ has been reported to occur as frequently as 0.49% in pregnancy [4]. At Jackson Memorial Hospital, University of Miami School of Medicine we have observed a relatively high incidence of cervical carcinoma among our pregnant patients. Several interesting factors related to disease during various periods of observation prompted a review of our experience. ’ The opinions expressed herein represent those of the authors and are not necessarily the Bureau of Medicine and Surgery, or the U. S. Navy as a whole. p Advanced Clinical Fellow, American Cancer Society. Present address: Department trics and Gynecology, Naval Hospital, Key West, Florida. ” U. S. Navy-sponsored Fellow, Gynecologic Oncology. Copyright All rights
@ 1973 by Academic Press, Inc. of reproduction in any form reserved.
283
those of Obste-
of
284
DUDAN
MATERIALS
ET
AL.
AND
METHODS
During the 11-year period from 1960 through 1970 the Department of Obstetrics and Gynecology, University of Miami School of Medicine has diagnosed and managed 122 patients with carcinoma of the cervix associated with pregnancy. Only those patients with a diagnosis of either in situ or invasive carcinoma during pregnancy are included. Patients who had carcinoma discovered during the early postpartum period are excluded from this study. Of the 122 patients, 99 were diagnosed as having carcinoma in situ and 23 had invasive carcinoma. Thus, the incidence of cervical carcinoma in pregnancy at our institution in 122 per 52,500 deliveries or 0.238%. For in situ carcinoma, it is 99 per 52,500 deliveries (0.192%), and for invasive carcinoma it is 23 per 52,500 deliveries (0.046%). The diagnosis of cancer in pregnancy at this institution is usually made as a result of routine cytologic screening in the prenatal clinics. Ninety-five percent of our patients were referred because of abnormal cytology. Five percent had symptoms of vaginal bleeding which ultimately led to the diagnosis of carcinoma. This experience would reemphasize the importance of early prenatal care, routine cytologic screening in all pregnant patients, and through evaluation of all patients with vaginal bleeding. Women with suspicious or positive cytology during pregnancy receive the same diagnostic workup as the nonpregnant patient. Punch biopsies of any suspicious lesion or area that fails to take a Schiller stain are performed. If the punch biopsy fails to show invasive carcinoma, cold knife cone biopsy is performed. Our experience with cone biopsy during pregnancy has been reported earlier [Sl. During the time covered by this study colposcopy was not available in our clinic. Currently all patients with atypical, suspicious, or positive cytology are colposcoped and selective biopsies performed in an attempt to reduce the number of cone biopsies necessary.
AGE Age (years)
OF PATIENTS Stage
0
WITH Stage
TABLE CERVICAL IA”
I NEOPLASIA Stage
IB
Stage
1
-
17-19 20-24 25-29 30-34 35-40 40-44
4 23 38 20 8 6
Total
99
6
15
Mean age (year) 29.6
29.0
30.0
31.9
’ For the purposes of stromal invasion.
of this
1 2 2
4 7 2 1
1
report,
Stage
IN PREGNANCY
IA is limited
to those
IIB
Stage
IIIB
1 1
cases
showing
1
less than
1 mm
CARCINOMA
OF
CERVIX
AND
285
PREGNANCY
The patient age range was from 17 to 44 years with a mean age of 29.6 years. There were 47 Caucasians and 75 Negroes. Parity ranged from 0 to 12 with a mean parity of 4. Table I is an analysis of the age distribution of our patients with cervical cancer during pregnancy. The mean age of patients with in situ carcinoma is 29 years and for Stage IA and IB carcinoma is 30.9 years. It is of interest that the mean age of patients with early invasive cancer is essentially the same as those with in situ carcinoma. Of our patients, 17% were found to have carcinoma of the cervix in the first trimester, 30% in the second trimester, and 53% in the third trimester. Our general plan of management for patients with carcinoma in situ is to allow the pregnancy to proceed to term and allow vaginal delivery. Definitive therapy for the carcinoma in situ is either abdominal or vaginal hysterectomy approximately 12 weeks postpartum depending on the patient’s age, parity, desire for further pregnancy, and follow-up cytologic examinations. Stage IA less than 1 mm stromal invasion, is treated by cesarean section extrafascial hysterectomy at term. Stage IB and IIA carcinoma are usually treated by radical hysterectomy and bilateral pelvic lymphadenectomy. Radiotherapy is utilized for more advanced invasive disease or for patients who have medical contraindications or refuse radical operation. RESULTS Carcinoma
in Situ
During the period of this review, 21 abdominal hysterectomies and 30 vaginal hysterectomies were performed for carcinoma in situ. Of these, three abdominal hysterectomies were performed in the immediate postpartum period and four cesarean section hysterectomies were performed in “highrisk” patients. We define our high-risk patient as one who by past medical records will return to the clinics or hospital only for emergency care or for prenatal care late in her pregnancy. One abdominal hysterectomy was performed in early pregnancy for therapeutic abortion, the carcinoma in situ being incidental and one cesarean hysterectomy was performed upon a paTABLE II ADVANCEMENT OF DISEASE IN FOLLOW-UP OF CERVICAL CANCER DIAGNOSED DURING PREGNANCY Patient 1. 2. 3. 4. 5. 6. 7. 8.
L.P. J.H. G.C. F.H. S.B. M.H. R.W. M.E. * P.G. = Pregnancy.
Stage
P.G.” 0 0 0 0 0 0 IB IB
Stage
Following IA IB IB IB IB IIA IIA IIIB
P.G.
Time 2 2 5 1 5 6 2 6
interval months months months year years years months months
286
DUDAN
ET
AL.
tient undergoing elective repeat cesarean section. Of those patients treated, 32 (63%) had residual carcinoma in situ in the surgical specimen while 19 (37%) had the disease removed by the cone biopsy. Six patients with a diagnosis of in situ carcinoma during pregnancy were found to have more advanced disease at a later date (Table II). Patients 1 and 2 were found to have persistent positive cytology in the postpartum period and repeat diagnostic workup revealed Stage IA and Stage IB carcinoma, respectively. Patients 3,4, 5, and 6 had a delay interval of from 5 months to 6 years after delivery which was directly related to patient delay and refusal of follow-up examinations. Therefore, of the 99 patients diagnosed as having in situ carcinoma during pregnancy, 51 have had definitive therapy, six had more advanced disease in an interval from 2 months to 6 years after delivery, and 42 patients are under continued observation. Invasive
Carcinoma
Six patients were found to have Stage IA cervical carcinoma (less than 1 mm stromal invasion). Five of the six were treated by cesarean section extrafascial hysterectomy at term and the other patient had an abdominal hysterectomy after a cone biopsy in early pregnancy when bleeding could not be controlled by more conservative measures. To date this management has been successful since all patients remain free of disease at the time of this report. Seventeen patients had a diagnosis of frankly invasive cervical carcinoma during pregnancy. In this group four patients underwent cesarean section radical hysterectomy at or near term, two patients had a hysterotomy and radical hysterectomy in the second trimester, two patients had radical hysterectomy in the first trimester, and two patients had a radical hysterectomy in the immediate postpartum period when the diagnosis of invasive cancer was made at the time of delivery. Five patients were treated with primary radiotherapy during pregnancy and two patients refused any form of therapy at the time of initial diagnosis. In the radical hysterectomy group the operating time has ranged from 4 to 6 hr 30 min with an average operating time of 5 hr 11 min. Blood loss ranged from 1500 to 6000 cc with an average of 2835 cc. The postoperative hospital stay ranged from 11 to 22 days with an average stay of 15.5 days. There were three postoperative complications in this group. Two patients had superficial wond infections and one patient had a suspected but unconfirmed pulmonary embolus. In long-term follow-up one patient developed serum hepatitis, but recovered completely. No patient undergoing radical hysterectomy has developed a major complication such as ureterovaginal fistula, vesicovaginal fistula, or bowel obstruction. Two patients were found to have metastatic tumor to the pelvic lymph nodes and received postoperative radiotherapy to the pelvis as suggested by Guttmann [9] and Kelso [lo]. Of these two patients, one has died of diffuse metastatic carcinoma. The recurrent tumor was diagnosed within 13 years and the patient died within 2+ years after primary therapy, This time interval for recurrent disease is consistent with our observations in patients
CARCINOMA
OF
CERVIX
AND
PREGNANCY
287
having radical hysterectomy in the nonpregnant state. At the time of this writing all patients have been followed for nearly 3 years and 9 of the 10 radical hysterectomy patients have no evidence of recurrent disease. Five patients have been treated with primary radiotherapy during pregnancy. Of the five patients treated, three were clinical Stage IB, 1 was Stage IIB, and 1 was Stage IIIB. In this group four patients have died. One patient died of recurrent carcinoma. The other three deaths were due to complications of radiotherapy which include hemorrhage secondary to necrosis and rupture of the hypogastric artery, hemorrhage secondary to radiation changes in the bladder and rectum, and the third involving multiple small-bowel fistulas. The surviving patient had multiple complications of rectovaginal and vesicovaginal fistulas which required colostomy and urinary diversion, but is alive 9 years after primary therapy. Postpartum-Zntrapartum
Period
As noted in Table II eight patients with progression of disease were treated in the postpartum-intrapartum period. Six patients had a diagnosis of Stage 0 carcinoma during pregnancy, but were found to have more advanced disease in a follow-up period varying from 2 months to 6 years. Two patients had a diagnosis of Stage IB invasive carcinoma during pregnancy, but refused any form of initial therapy. Patient 1 was found to have Stage IA carcinoma, and abdominal hysterectomy was performed. She currently is clinically free of recurrent disease. Patients 2, 3, 4, and 5 were found to have Stage IB carcinoma in an interval of from 2 months to 5 years after delivery. These patients were treated by radical hysterectomy and bilateral pelvic lymphadenectomy. All four patients were free of metastatic disease to the pelvic lymph nodes and clinically remain free of disease in a follow-up period of at least 3 years. The remaining three patients were treated with radiotherapy, two for Stage IIA and one for Stage IIIB carcinoma. In this group two patients have died of recurrent or persistent disease while one patient is free of disease in a followup period of over 3 years. DISCUSSION Preliminary to any discussion of clinical experience at Jackson Memorial Hospital one must understand the usual patient we encounter. Most patients are from low socioeconomic groups including many migrant laborers. Medical care is sought only on an emergency basis or in late pregnancy. We believe this reflects in the fact that only 17% of our patients had a diagnosis of cancer made during the first trimester while 53% were diagnosed in the third trimester. Further difficulty is encountered in obtaining optimal follow-up or instituting primary therapy as evidence by the number of Stage 0 carcinoma patients who have not had definitive therapy and the two patients with early invasive carcinoma who refused therapy until the disease was more advanced. For these and other reasons that will be pointed out, our institution plans a more aggressive approach to the gravid patient with in situ carcinoma of the cervix.
288
DUDAN
ET
AL.
In the future we plan to use cesarean hysterectomy or postpartum hysterectomy for patients with Stage 0 carcinoma of the cervix, unless there is absolute patient reliability for follow-up care. We believe this is justified for the following reasons: (1) Most patients are of relatively high parity. (2) Many patients will not return for follow-up care. (3) Some patients will experience progression of disease as outlined in Table 2. (4) Of those hysterectomies performed for Stage 0 cancer, 63% had residual carcinoma in the surgical specimen. This probably indicates that a cone biopsy performed during pregnancy is not as extensive as a cone biopsy in the nonpregnant patient. 5. There have been no postoperative deaths in patients treated in this manner although we may expect some increased postoperative morbidity when compared to the hysterectomy performed at 12 weeks postpartum . We will continue to treat Stage IA (microinvasive) carcinoma by cesarean hysterectomy. Our results with radical hysterectomy for Stage IB-IIA carcinoma would seem to justify the procedure although the total number of patients treated in this manner is small. The major differences in measurable parameters in comparing the radical hysterectomy in the pregnant patient to our nonpregnant patient is an increase in total operating time and increased blood loss at operation. The absence of major complications, such as ureterovaginal fistula, vesicovaginal fistula, or bowel obstruction, combined with an apparent high survival rate would further justify this approach. We feel it is impossible to compare patients that have had radical operation to those who receive radiotherapy. A degree of patient selection always exists and those patients treated with radiotherapy have the benefit of clinical staging only while operative candidates have their stage of disease confirmed by preliminary abdominal and pelvic exploration. In this series the major complications secondary to radiation therapy have been very high and the survival rate has been very low. The radiation dosimitry used was in the levels recommended by other institutions, however, our results were not as favorable [ll]. We have no explanation for our poor results with radiotherapy,
REFERENCES 1. HAYDEN, C. E. Carcinoma of the 71, 780 (1956). 2. KISTNER, K. W., CORBACH, A. Gynecol. 9,554 (1957). 3. MCDUFF, A. C., CARNEY, W. I., O&et. Gynecol. 8, 196 (1965). 4. MAKSH, M., AND FITZGERALD, nancy. Cancer 9, 1195 (1956).
cervix C., AND
associated SSIITH,
AND WATERMAN, P. J. Carcinoma
with
pregnancy.
V. Cervical G. W. Cancer
Amer.
cancer
/. Obstet.
Cynecol.
in pregnancy.
Obstet.
of the cervix
in situ of the human
uterine
and pregnancy. cervix
in preg-
CARCINOMA
OF
CERVIX
AND
PREGNANCY
289
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