GYNECOLOGIC
ONCOLOGY
8,
84-86 (1979)
The Treatment of Microinvasive Squamous Carcinoma of the Uterine Cervix DAVID
R. POPKIN, M.D.,
C.M., FRCS(C), FACOG, ROBERT FRCS(C), FACOG, AND J. P. A. LATOUR, M.D.,
M.D., Division
Cell
of Gynecological University,
C.M.,
FRCS(C),
Oncology. Department Royal Victoria Hospital,
PILORGE,
FACS
of Obstetrics and Gynecology, Montreal, Quebec, Canada
McGill
Received September 22, 1978 Between 1947 and 1971 254 cases of microinvasive carcinoma of the uterine cervix were treated in this institution. Cervical cytology was used to detect the cervical abnormality and the diagnosis of microinvasion was established by cone biopsy. During this time period microinvasion was defined as the breakthrough of the basement membrane and the penetration of neoplastic epithelium into the stroma to a depth of no greater than 5 mm, and excluded those cases which had lymph or blood vessel involvement, a dentritic or staghorn pattern, many epithelial cells in clusters in the stroma, or the presence of confluence. Of the 254 cases, 250 were followed for 5 years or more. Treatment methods for microinvasive cervical cancer over this time period included surgery alone, radiotherapy alone, or a combined approach using both surgery and radiotherapy. None of the 125 cases treated by surgery alone have died of cervical cancer. It is concluded that microinvasive carcinoma, as defined in this study, can be cured by conservative surgical means.
Microinvasive carcinoma of the uterine cervix is recognized as a clinical entity and is referred to as stage IA in the FIG0 staging for cervical cancer. The recognition of this cancer should be based on a pattern of growth and not just on the depth of infiltration of neoplastic epithelium below the basement membrane. The significance of distinguishing this lesion from other stage I cancers is that the true microinvasive lesion should not metastasize to the lymph nodes and therefore can be treated in a manner similar to carcinoma in situ. The purpose of this study is to report the results obtained in the management of microinvasive carcinoma of the cervix from 1947 to 1971. During this period of time the concept of carcinoma in situ and microinvasive cancer was developed, neither entity being recognized by the international classification in the earlier years of this study [ 11. The concept that microinvasive cancer had a different biologic potential than other invasive stage I cancers of the cervix has been maintained throughout the time of this study and the following definition pertains to the material presented. Our concept of microinvasive cancer of the cervix embodies the breakthrough of the basement membrane and the penetration of neoplastic epithelial cells into the stroma to a depth of no greater than 5 mm, as 84 0090-8258/79/040084-03$01.00/O Copyright All rights
@ 1979 by Academic Press, Inc. of reproduction in any form reserved
SQUAMOUS
CELL
CARCINOMA
OF
THE
CERVIX
85
measured from the basement membrane. Not to be included in stage IA are those cases which show lymph or blood vessel involvement, a dentritic or staghorn pattern of growth, many epithelial cells in small clusters in the stroma, or the presence of confluence. These latter cases are stage IB even if the depth of penetration is less than 5 mm. MATERIALS
AND METHODS
We have reviewed all cases diagnosed as microinvasive carcinoma of the cervix from January 1947 to December 1971. All were diagnosed and treated at the Royal Victoria Hospital. The same pathologist examined the histology and made the diagnosis during this entire period. During the study period there were 1,272 cases of invasive cervical cancer of which 254 were microinvasive cancer and 335 were stage IB. There were also 617 cases of carcinoma i/r sifu. Of the 254 cases of microinvasion 92% were detected by exfoliative cervial cytology. In 3% the cervical cytology was negative and in 5% there was no record of the results of cytology. All diagnoses were made from cone biopsy specimens except for 3 of the cases treated by radiotherapy in which there were no records of how the diagnoses were established. The 254 patients were treated by one of three methods. There were 125 patients treated by surgery alone, 105 by abdominal hysterectomy with a vaginal cuff, 1 by cesarean section and hysterectomy, 8 by removal of the cervical stump with vaginal cuff, 8 by cone biopsy, and 3 by radical hysterectomy and pelvic lymphadenectomy. There were 63 patients treated by radiotherapy alone using intracavitary radium followed by external radiotherapy. A combination of radiotherapy and surgery was used to treat 66 patients. RESULTS
Of the 125 patients treated by surgery alone all were alive and free from disease 5 years after treatment. There were 2 patients lost to follow-up before 5 years, i.e., at 1 year and 2 years. There were 9 patients lost to follow-up between 5 and IO years and 4 more lost to follow up after 10 years. Eight of the remaining 110 patients have died, all of known causes, none with evidence of cervical cancer. In this surgically treated group there were no deaths from cervical cancer and no recurrences. The follow-up of the 125 patients is 88% for 10 years and 98% for 5 years. There were 63 cases treated by radiotherapy alone and all were followed for 15 or more years. None died of cervical cancer within 5 years of treatment. Two patients died of cervical cancer at 15 and 20 years after treatment by radiotherapy. They both had recurrent disease localized to the pelvis. There were 66 patients treated by radiotherapy followed by abdominal hysterectomy. Two patients died within 5 years of treatment; one of postoperative complications 3 weeks following surgery, the other of a primary brain tumor 4 years after treatment. Two patients were lost to follow-up within 5 years of treatment. Of the remaining 62 patients three were lost to follow-up at 5, 10, and 23 years. Four died of causes other than cancer. In this group there were no deaths from cervical cancer but the morbidity following treatment was greater than in the other two treatment groups (see Table 1).
86
POPKIN,
PILORGE,
AND
TABLE RESULTS
Treatment
method
Surgery alone Radiotherapy alone Radiotherapy and surgery
OF TREATMENT
Number 125 63 66
LATOUR
1
OF 254 CASES
5-year
OF MICRO(NVASIVE
CANCER
survival
123(98.5%) 63( 100%) 62(94%)
Remarks Two
patients
lost to follow-up Two patients lost to follow-up; two patients died of known causes
DISCUSSION
There is not, at this time, total agreement as to the definition of microinvasive cervical cancer [2,3]. From our data it would appear that provided the depth of invasion of neoplastic epithelium below the basement membrane does not exceed 5 mm and there is no blood vessel or lymphatic involvement, no confluent or staghorn pattern of growth, and no clusters of neoplastic epithelium in the stroma, the lesion can be treated by conservative surgical methods. If the four patients lost to follow-up in the first 5 years after treatment are excluded there were no deaths and no recurrences for 5 years in any of the three treatment groups. It seems evident that the occurrence of lymph node metastases in this carefully selected group of patients is extremely rare. A review of the literature indicates that the incidence of lymph node metastases in cases where the depth of infiltration below the basement membrane is 1 mm or less is zero [4-61. Data also suggest that lymphatic or blood vessel permeation is as important as penetration of the basement membrane in predicting likelihood of spread beyond the cervix [7]. The actual depth of penetration below the basement membrane, be it 1, 3, or 5 mm, is probably of less import than the selection of patients with the growth patterns of neoplastic epithelium below the basement membrane described in the definition of microinvasive cervical cancer used in this and other studies 181. The presence of these characteristic growth patterns indicates a greater likelihood of spread beyond the cervix regardless of the depth of infiltration and therefore is an indication for radical therapy. REFERENCES J. P. A. Results in the management of preclinical carcinoma of the cervix, Amer. J. Obstet. Gynecol. 81, 511-514 (1961). Savage, E. W. Microinvasive carcinoma of the cervix, Amer. J. Obstet. Gynecol. 113, 708-717 (1972). Kirk, M. E. Progress in human pathology, Gynecol. Hum. Puthol. 5, 253-257 (1974). Mussey, E., Soule, E. H., and Welch, J. S. Microinvasive carcinoma of the cervix. Late results of operative treatment in 91 cases, Amer. J. Obstet. Gynecol. 104, 738-742 (1969). Averette, H. E., Nelson, J. H., Ng, A. B. P., et al. Diagnosis and management of microinvasive (stage IA) carcinoma of the uterine cervix, Cuncer 38, 414-425 (1976). Wilkinson, E. J., and Komoroski, R. A. Borderline microinvasive carcinoma of the cervix, Obstet. Gynecol. 51, 472-475 (1978). Bohm, J. W., Krapp, P. J., Lee, F. Y. L., et al. Lymph node metastases in microinvasive epidermoid cancer of the cervix, Obstet. Gynecol. 48, 65-67 (1976). Marcuse, P. M. Incipient microinvasive carcinoma of the uterine cervix, Obstet. Gynecol. 37, 360-367 (1971).
1. Latour, 2. 3. 4. 5. 6. 7. 8.
ONCOLOGY
8,
84-86 (1979)
The Treatment of Microinvasive Squamous Carcinoma of the Uterine Cervix DAVID
R. POPKIN, M.D.,
C.M., FRCS(C), FACOG, ROBERT FRCS(C), FACOG, AND J. P. A. LATOUR, M.D.,
M.D., Division
Cell
of Gynecological University,
C.M.,
FRCS(C),
Oncology. Department Royal Victoria Hospital,
PILORGE,
FACS
of Obstetrics and Gynecology, Montreal, Quebec, Canada
McGill
Received September 22, 1978 Between 1947 and 1971 254 cases of microinvasive carcinoma of the uterine cervix were treated in this institution. Cervical cytology was used to detect the cervical abnormality and the diagnosis of microinvasion was established by cone biopsy. During this time period microinvasion was defined as the breakthrough of the basement membrane and the penetration of neoplastic epithelium into the stroma to a depth of no greater than 5 mm, and excluded those cases which had lymph or blood vessel involvement, a dentritic or staghorn pattern, many epithelial cells in clusters in the stroma, or the presence of confluence. Of the 254 cases, 250 were followed for 5 years or more. Treatment methods for microinvasive cervical cancer over this time period included surgery alone, radiotherapy alone, or a combined approach using both surgery and radiotherapy. None of the 125 cases treated by surgery alone have died of cervical cancer. It is concluded that microinvasive carcinoma, as defined in this study, can be cured by conservative surgical means.
Microinvasive carcinoma of the uterine cervix is recognized as a clinical entity and is referred to as stage IA in the FIG0 staging for cervical cancer. The recognition of this cancer should be based on a pattern of growth and not just on the depth of infiltration of neoplastic epithelium below the basement membrane. The significance of distinguishing this lesion from other stage I cancers is that the true microinvasive lesion should not metastasize to the lymph nodes and therefore can be treated in a manner similar to carcinoma in situ. The purpose of this study is to report the results obtained in the management of microinvasive carcinoma of the cervix from 1947 to 1971. During this period of time the concept of carcinoma in situ and microinvasive cancer was developed, neither entity being recognized by the international classification in the earlier years of this study [ 11. The concept that microinvasive cancer had a different biologic potential than other invasive stage I cancers of the cervix has been maintained throughout the time of this study and the following definition pertains to the material presented. Our concept of microinvasive cancer of the cervix embodies the breakthrough of the basement membrane and the penetration of neoplastic epithelial cells into the stroma to a depth of no greater than 5 mm, as 84 0090-8258/79/040084-03$01.00/O Copyright All rights
@ 1979 by Academic Press, Inc. of reproduction in any form reserved
SQUAMOUS
CELL
CARCINOMA
OF
THE
CERVIX
85
measured from the basement membrane. Not to be included in stage IA are those cases which show lymph or blood vessel involvement, a dentritic or staghorn pattern of growth, many epithelial cells in small clusters in the stroma, or the presence of confluence. These latter cases are stage IB even if the depth of penetration is less than 5 mm. MATERIALS
AND METHODS
We have reviewed all cases diagnosed as microinvasive carcinoma of the cervix from January 1947 to December 1971. All were diagnosed and treated at the Royal Victoria Hospital. The same pathologist examined the histology and made the diagnosis during this entire period. During the study period there were 1,272 cases of invasive cervical cancer of which 254 were microinvasive cancer and 335 were stage IB. There were also 617 cases of carcinoma i/r sifu. Of the 254 cases of microinvasion 92% were detected by exfoliative cervial cytology. In 3% the cervical cytology was negative and in 5% there was no record of the results of cytology. All diagnoses were made from cone biopsy specimens except for 3 of the cases treated by radiotherapy in which there were no records of how the diagnoses were established. The 254 patients were treated by one of three methods. There were 125 patients treated by surgery alone, 105 by abdominal hysterectomy with a vaginal cuff, 1 by cesarean section and hysterectomy, 8 by removal of the cervical stump with vaginal cuff, 8 by cone biopsy, and 3 by radical hysterectomy and pelvic lymphadenectomy. There were 63 patients treated by radiotherapy alone using intracavitary radium followed by external radiotherapy. A combination of radiotherapy and surgery was used to treat 66 patients. RESULTS
Of the 125 patients treated by surgery alone all were alive and free from disease 5 years after treatment. There were 2 patients lost to follow-up before 5 years, i.e., at 1 year and 2 years. There were 9 patients lost to follow-up between 5 and IO years and 4 more lost to follow up after 10 years. Eight of the remaining 110 patients have died, all of known causes, none with evidence of cervical cancer. In this surgically treated group there were no deaths from cervical cancer and no recurrences. The follow-up of the 125 patients is 88% for 10 years and 98% for 5 years. There were 63 cases treated by radiotherapy alone and all were followed for 15 or more years. None died of cervical cancer within 5 years of treatment. Two patients died of cervical cancer at 15 and 20 years after treatment by radiotherapy. They both had recurrent disease localized to the pelvis. There were 66 patients treated by radiotherapy followed by abdominal hysterectomy. Two patients died within 5 years of treatment; one of postoperative complications 3 weeks following surgery, the other of a primary brain tumor 4 years after treatment. Two patients were lost to follow-up within 5 years of treatment. Of the remaining 62 patients three were lost to follow-up at 5, 10, and 23 years. Four died of causes other than cancer. In this group there were no deaths from cervical cancer but the morbidity following treatment was greater than in the other two treatment groups (see Table 1).
86
POPKIN,
PILORGE,
AND
TABLE RESULTS
Treatment
method
Surgery alone Radiotherapy alone Radiotherapy and surgery
OF TREATMENT
Number 125 63 66
LATOUR
1
OF 254 CASES
5-year
OF MICRO(NVASIVE
CANCER
survival
123(98.5%) 63( 100%) 62(94%)
Remarks Two
patients
lost to follow-up Two patients lost to follow-up; two patients died of known causes
DISCUSSION
There is not, at this time, total agreement as to the definition of microinvasive cervical cancer [2,3]. From our data it would appear that provided the depth of invasion of neoplastic epithelium below the basement membrane does not exceed 5 mm and there is no blood vessel or lymphatic involvement, no confluent or staghorn pattern of growth, and no clusters of neoplastic epithelium in the stroma, the lesion can be treated by conservative surgical methods. If the four patients lost to follow-up in the first 5 years after treatment are excluded there were no deaths and no recurrences for 5 years in any of the three treatment groups. It seems evident that the occurrence of lymph node metastases in this carefully selected group of patients is extremely rare. A review of the literature indicates that the incidence of lymph node metastases in cases where the depth of infiltration below the basement membrane is 1 mm or less is zero [4-61. Data also suggest that lymphatic or blood vessel permeation is as important as penetration of the basement membrane in predicting likelihood of spread beyond the cervix [7]. The actual depth of penetration below the basement membrane, be it 1, 3, or 5 mm, is probably of less import than the selection of patients with the growth patterns of neoplastic epithelium below the basement membrane described in the definition of microinvasive cervical cancer used in this and other studies 181. The presence of these characteristic growth patterns indicates a greater likelihood of spread beyond the cervix regardless of the depth of infiltration and therefore is an indication for radical therapy. REFERENCES J. P. A. Results in the management of preclinical carcinoma of the cervix, Amer. J. Obstet. Gynecol. 81, 511-514 (1961). Savage, E. W. Microinvasive carcinoma of the cervix, Amer. J. Obstet. Gynecol. 113, 708-717 (1972). Kirk, M. E. Progress in human pathology, Gynecol. Hum. Puthol. 5, 253-257 (1974). Mussey, E., Soule, E. H., and Welch, J. S. Microinvasive carcinoma of the cervix. Late results of operative treatment in 91 cases, Amer. J. Obstet. Gynecol. 104, 738-742 (1969). Averette, H. E., Nelson, J. H., Ng, A. B. P., et al. Diagnosis and management of microinvasive (stage IA) carcinoma of the uterine cervix, Cuncer 38, 414-425 (1976). Wilkinson, E. J., and Komoroski, R. A. Borderline microinvasive carcinoma of the cervix, Obstet. Gynecol. 51, 472-475 (1978). Bohm, J. W., Krapp, P. J., Lee, F. Y. L., et al. Lymph node metastases in microinvasive epidermoid cancer of the cervix, Obstet. Gynecol. 48, 65-67 (1976). Marcuse, P. M. Incipient microinvasive carcinoma of the uterine cervix, Obstet. Gynecol. 37, 360-367 (1971).
1. Latour, 2. 3. 4. 5. 6. 7. 8.
