GYNECOLOGIC ONCOLOGY 35, 314-320 (1989)

A Prospective Surgical Pathological Study of Stage I Squamous

Carcinoma of the Cervix: A Gynecologic
Oncology Group Study*
G. DELGADO, M.D.,’ B. N. BUNDY, PH.D.,* W. C. FOWLER, JR., M.D.,3 F. B. STEHMAN, M.D.,4
B. SEVIN, M.D.,5 WILLIAM T. CREASMAN,M.D.,6 F. MAJOR, M.D.,’ P. DISAIA, M.D.,8
AND R. ZAINO, M.D.9
‘Division of Gynecologic Oncology, Georgetown University,
Vincent T. Lombardi Cancer Research Center, 3800 Reservoir Road, NW,
Washington, DC
’ Roswell Park Memorial Institute, Buffalo, New York
3 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel
Hill, North Carolina 27514
’ Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Indiana University Medical Center,
Indianapolis, Indiana 46202
’ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Miami School of Medicine, Miami, Florida
6 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina
’ Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, and Gynecology Tumor Service,
Denver General Hospital, Denver, Colorado
a Department of Obstetrics and Gynecology, University of California, Irvine Cancer Center, Orange, California
9 Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033

Received July 18, 1988

Thirty-three institutions collaborating in the Gynecologic On-
cology Group gathered surgical and pathological data on 1125
patients with primary, previously untreated, histologically con-
fhmed stage I cervical carcinoma with more than 3 mm of in-
vasion who were selected to undergo radical hysterectomy and
paraaortic and pelvic lymphadenectomy. Of the 940 eligible, ev-
aluable patients, 732 had squamous carcinoma. Of the study
group, 87 (12%) did not undergo radical hysterectomy because
of gross disease beyond the uterus or microscopic aortic node
involvement documented at exploratory laparotomy. Among the
645 patients undergoing pelvic and paraaortic lymphadenectomy
and radical hysterectomy, five risk factors were significantly as-
sociated with microscopic pelvic lymph node metastasis: depth
of invasion (P = O.OOOl),parametrial involvement (P = O.OOOl),
capillary-lymphatic space invasion (P = O.OOOl),tumor grade
(P = O.Ol), and gross versus occult primary tumor (P = 0.009).
The factors identified as independent risk factors for pelvic lymph
node metastasis by multivariate analysis were capillary-lymphatic
space involvement (P < O.OOOl),depth of invasion (P < O.OOOl),
parametrial involvement (P = O.OOOS), and age (P = 0.02). The
model was used to predict the chance of a patient having nodal
metastasis for any combination of risk factors. Q 19139academic PMS,
Inc.
* Address reprint requests to GOG Headquarters, Suite 1945, 1234
Market St., Philadelphia, PA 19107.
314
0090-8258/89$1.50
Copyright 0 1989by Academic Press, Inc.
All rights of reproductionin any form reserved.
INTRODUCTION
The several reports in the literature presenting a sur-
gical-pathological analysis of stage I cervical cancer are
mostly retrospective reviews of cases accumulated over
a 5- to 20-year period [l-6]. From 1981 to 1984, thirty-
three institutions associated with the Gynecologic On-
cology Group (GOG) undertook a prospective study of
the surgical and pathological data on patients with pri-
mary, previously untreated, histologically confirmed
stage I cervical cancer. Data on these patients who
underwent radical hysterectomy, pelvic lymph adenec-
tomy, and paraaortic lymphadenectomy were subjected
to multivariate analysis to identify independent risk fac-
tors and estimate the level of risk for pelvic lymph node
metastasis.
MATERIAL AND METHODS
From May 1981 to February 1984, the Gynecologic
Oncology Group registered preoperatively 1125 patients
with primary, previously untreated, histologically con-
firmed FIG0 stage I cervical cancer with more than 3
mm of invasion. The protocol did not require registration
of all stage IB cervical cancers of the cervix.
 SQUAMOUS CARCINOMA
The protocol directed that all patients were to undergo
radical hysterectomy, paraaortic and pelvic lymphade-
nectomy, and peritoneal cytology. Patients with frozen-
section confirmation of tumor involving structures other
than the uterus, cervix, and pelvic nodes were to have
only exploration and appropriate biopsies to confirm the
extent of the disease. Patients with fixed, nonresectable
pelvic nodes, confirmed by frozen section, were to re-
ceive only pelvic node biopsy, paraaortic node sampling,
and exploration of the abdomen and pelvis.
The radical hysterectomy consisted of removal of the
uterus and contiguous parametrial tissue to its most lat-
eral extent, along the paravaginal tissue and the upper
portion of the vagina and the proximal uterosacral lig-
aments. The uterine artery was transected at its origin
lateral to the ureter. The ureter was unroofed from its
entry into the broad ligament to its intramural portion
in the bladder and dissected laterally from its attachment
to the cardinal ligament [7-121.
Pelvic lymphadenectomy was performed by bilateral
removal of all nodal tissue and skeletonization of all
vessels from the midportion of the common iliac artery
to the deep circumflex iliac vein. The lateral limit of the
dissection was the psoas muscle. The obturator fossa
was cleared to the level of the obturator nerve [ 131.
For the paraaortic lymphadenectomy, the peritoneum
was entered at the root of the small bowel mesentery at
the ileocecal junction. The peritoneal invasion continued
toward the bifurcation of the aorta and extended ce-
phalad for 5 cm. The mesentery of the small bowel was
retracted, and aorta and vena cava were identified. After
the lateral retraction of the right ureter, the fatty tissue
containing the lymph nodes was removed anterior and
lateral to the vena cava. The dissection was performed
on the left side, anterior and lateral to the aorta, after
identification and retraction of the left ureter and ovarian
blood vessels.
Clinical data collected included gross description,
greatest diameter of the primary tumor, patient age, and
GOG performance status of 0, 1, and 2, which is equiv-
alent to the Karnofsky scale of 90+ 100, 70+ 80, and
50 + 60, respectively. The participating institutions sub-
mitted operative reports, pathological slides and reports,
discharge summaries, and follow-up data on postoper-
ative treatment, complications, and recurrence to the
GOG Gynecologic Management Committee which re-
viewed all the material for study. The Protocol Chairman
reviewed the data for protocol adherence and coding
accuracy. Two pathologists from the GOG Pathology
Committee reviewed and analyzed the pathology
material.
The tumors were classified according to cell type as
follows: squamous cell carcinoma, adenocarcinoma, ad-
enosquamous carcinoma, and other. A pathologic grade
OF THE CERVIX 315
of well, moderately or poorly differentiated was assigned
to each of the tumors using a modification of Broders’
classification [ 14,151. Squamous carcinomas were cate-
gorized as large cell nonkeratinizing, large cell keratin-
izing, or small cell, according to the criteria of Reagan
et al. [16,17].
The total thickness of the cervix was measured with
a millimeter scale. The maximum depth of invasion of
tumor into the cervical stroma was assessed, with the
site of penetration defined as that point where the base-
ment membrane of the surface epithelium or underlying
gland was disrupted by malignant cells. Also, the max-
imum depth of invasion was categorized by fractional
thickness of the cervix as follows: any penetration up
to and including one-third the thickness of the cervix
was recorded as inner third, greater than one-third up
to and including two-thirds was recorded as middle third,
and greater than two-thirds was recorded as outer third.
Capillary-lymphatic space invasion was recorded when
neoplastic cells were identified microscopically within
endothelium-lined spaces. Tumor involvement was de-
termined for the following structures: uterine cavity, pel-
vic and paraaortic nodes, fallopian tubes, ovaries, par-
ametrium, and surgical margins.
The x2 test [18] was used to evaluate the association
of various factors with both the presence of tumor be-
yond the uterus, cervix, and pelvic nodes and the pres-
ence of positive pelvic lymph nodes. The logistic model
[19] was employed to simultaneously evaluate these as-
sociations to determine their independent contributions.
RESULTS
After central GOG review, the initial study group of
1125 patients was reduced to 940 evaluable cases (Table
1). One hundred twenty-one patients were eliminated
from the study because they did not meet preoperative
eligibility requirements: 15 patients did not have the cor-
rect FIG0 stage, 1 patient had a previous cancer, 8
patients had tumors with less than 3 mm of invasion, 9
patients had inadequate pathologic material to confirm
histology and invasion, 2 patients did not undergo sur-
gery, and 14 patients were registered postoperatively.
There were 49 patients who did not receive protocol
surgery because of intraoperative complications or other
circumstances unrelated to their disease. Postoperative
histologic evaluation eliminated 15 additional patients:
10 patients did not have cervical carcinoma (9 endome-
trial carcinoma, 1 uterine sarcoma); 3 patients had two
primary cancers, one each with endometrial, colonic, and
small bowel; and 2 patients were excluded because their
institutions did not submit the required materials.
Of the 940 evaluable patients, 732 (78%) had squamous
cell carcinoma. There were 117 (12%) patients with ad-
316 DELGADO ET AL.
TABLE 1
ExclusionsBasedon Eligibility, Surgical Procedures,Cell
Type, and Extent of Disease
Total entries 112.5
Exclusions
Preoperative 121
Surgical 49
Postoperative 15
Evaluable 940
Nonsquamous cell carcinomas
Adenocarcinoma 117
Adenosquamous 78
Other 13
Evaluable with squamous cell carcinoma
Gross disease beyond the uterus and
cervix or microscopic involvement of the
aortic nodes
Disease outside the pelvis
Positive aortic nodes 29
Other structures 7 carcinoma and no gross/aortic disease was also studied.
Disease confined to the pelvis
Pelvic structures 32
Gross pelvic nodes only 19
Study population with complete evaluation
of disease
enocarcinoma, 78 (8%) with adenosquamous carcinoma,
and 13 (1%) with tumors of other cell types. Those pa-
tients with squamous cell carcinoma are the focus of this
report. Those with nonsquamous cell carcinoma will be
addressed in a subsequent paper.
Among the 732 patients with squamous cell carcinoma,
87 (12%) had either gross disease beyond the uterus and
cervix or microscopic involvement of the aortic lymph
nodes. There were 29 (4%) patients with aortic node
metastasis (microscopic or gross) and 7 (1%) patients
with disease beyond the pelvis with negative aortic
nodes. Among patients with gross disease confined to
the pelvis (but beyond the uterus and cervix), 32 (4%)
had tumor implants, direct extension, or gross serosal
breakthrough and 19 (3%) patients had only gross tumor
in the pelvic lymph nodes (Table 1).
The frequency of patients with either gross disease
beyond the uterus and cervix or microscopic involve-
ment of the aortic nodes (gross/aortic disease) was de-
termined for various preoperative factors. The patient’s
GOG performance status, tumors more than 3 cm in
diameter, and histologic grade were positively correlated
with the frequency of gross/aortic disease. Ulcerated
tumors were associated with a lower frequency of
gross/aortic disease when compared with endophytic
and exophytic tumors.
Logistic analysis assessed the independent association
of the significant factors listed above for gross/aortic
disease. The factors that had independent significant as-
sociation were maximum diameter of the primary tumor,
GOG performance status, gross description of the pri-
mary tumor, and histologic tumor grade (listed in order
of most to least significant). The three most significant
factors were used to define risk groups in such a way
as to maximize the difference in the frequency of
gross/aortic disease. Among the 70 patients assigned to
the low-risk subgroup, defined as performance status 0,
grade 1 tumor, and tumor diameter less than 3 cm, 3
(4%) had gross/aortic disease. In contrast, 8 of 17 (47%)
patients with performance status of 1 or poorer, grade
3 tumor, and tumor diameter of 3 cm (high risk) had
gross/aortic disease. Although the high-risk group has
732 an 11 times greater chance of having gross/aortic dis-
ease, it constitutes only 2% of the study population. The
low-risk group makes up only 10%.
The distribution of the pathological factors in the 645
hysterectomy specimens of patients with squamous cell
There were 93 (14.4%), 373 (57.8%), and 179 (27.8%)
patients with histologic grade 1, 2, and 3 tumors, re-
spectively. For the classification of cell type, size, and
645 keratinizing status, 401 (62.2%) patients had large cell
nonkeratinizing tumors, 227 (35.2%) had large cell ker-
atinizing tumor, and 17 (2.6%) had either small cell or
other cell types. There were 100 (15.5%) patients with
microscopic pelvic nodal metastasis; of these, 45 (7.0%)
had two or more positive lymph nodes. There were 31.3,
33.0, and 35.7% of patients with superficial, middle-third,
and deep-third invasion into the cervix, respectively.
There were 74 (11.5%) patients with uterine extension,
20 (3.1%) with tumor at the surgical margins, 44 (6.8%)
with parametrial tumor involvement, and 276 (43.0%)
with capillary-lymphatic space involvement. Among the
627 patients who underwent peritoneal cytology, only 2
(0.3%) patients had malignant cells in the sample.
Gross versus occult primary tumor was the only clin-
ical factor found to be significantly correlated with pos-
itive pelvic lymph nodes. Age at diagnosis was close to
statistical significance when classified by decade (Table
2). Among pathological factors, histologic grade, depth
of invasion, tumor in the parametrium, and capillary-
lymphatic space involvement were all found to be sig-
nificantly correlated with positive lymph nodes (Table
3).
Logistic analysis assessed the independent association
of pre- and postsurgical factors to the status of pelvic
lymph nodes for patients with no gross/aortic disease.
The factors listed in Tables 2 and 3 that reached a sig-
nificance level of 0.2 or less were eligible to be included
in the model, but only factors that were significant at
the 0.05 level were included. The independent significant
factors were capillary-lymphatic space involvement
(P < O.OOOl),depth of invasion (P < O.OOOl),parametrial
involvement (P = O.OOS),and age (P = 0.02). Histologic
 SQUAMOUS CARCINOMA OF THE CERVIX 317

TABLE 2 TABLE 3
Frequency of Positive Pelvic Lymph Nodes by Host and Clinical Frequency of Positive Pelvic Lymph Nodes by Pathological
Factors for Patients with Squamous Cell Carcinoma, No Gross Factors for Patients with Squamous Cell Carcinoma, No Gross
Diseasebeyond the Uterus and Cervix, and Negative Aortic Nodes Diseasebeyond the Uterus and Cervix, and Negative Aortic Nodes
Frequency Frequency
with positive with positive
pelvic lymph pelvic lymph
Factor nodes* P Factor nodes” P

Total loo/645 (15.5) Histologic grade

Age 1 9/93 ( 9.7)
s 30 15/103 (14.6) 2 52,‘373 (13.9) 0.01
31-40 371233 (15.9) 3 39/179 (21.8)
41-50 32/149 (21.5) 0.07
Keratinizing/ceIl type size classification
51-60 12/102 (11.8)
Large cell nonkeratinizing 58/401 (14.5)
6l+ 4/58 ( 6.9)
Large cell keratinizing 391227 (17.2) 0.6
GOG performance status
Small cell/other 3/17 (17.6)
0 92/553 (16.6)
0.1
l-2 8/92 ( 8.7) Depth of invasion
Gross primary tumor C 5 mm 6/177 ( 3.4)
Occult 15/168 ( 8.9) 6-10 mm 36/238 (15.1)
0.009
Gross 851477 (20.9) 11-15 mm 30/135 (22.2) 0.0001
Maximum clinical tumor diameter 16-20 mm 19/49 (38.8)
0.1-1.0 cm 8/63 (12.7) 21+ mm 7131 (22.6)
1.1-2.0 cm 21/133 (15.8)
0.2h Inner third 9/199 ( 4.5)
2.1-3.0 cm 21/129 (16.3)
Middle third 28/210 (13.3) 0.0001
3.1+ cm 35/152 (23.0)
Outer third 601227 (26.4)
Gross primary tumor description
Endophytic 26/139 (18.7) Uterine extension
Exophytic 44/239 (18.4) 0.P Negative 83/567 (14.6)
Ulcerated 0.2
15,‘98 (15.3) Positive 16/74 (21.6)

a Number (%). Surgical margins

’ Patients with occult tumors were eliminated when computing the Negative 95/623 (15.2)
Positive 0.4
P value. 5/20 (25.0)
Parametrial extension
tumor grade was significant (P = 0.002) after two mod- Negative 81/599 (13.5)
Positive 0.0001
19144 (43.2)
ifications were made to the model: Grades 1 and 2 were
fixed at the same level of risk to be distinguished only Capillary/lymphatic spaces
from grade 3, and the increased risk associated with Negative 30/366 ( 8.2)
Positive 0.0001
70/276 (25.4)
grade 3 existed for superficial and middle-third invading
tumors only. Patient age was entered as a continuous Pelvic washings
Negative 97/625 (15.5)
variable, with both a linear and a squared term to quan- Positive
1.0
o/2 ( 0.0)
tify the decreasing risk at both ends of the age spectrum.
The parabolic-shaped risk function for age peaked at 38 ” Number (%).
years.
The risk of nodal metastasis was more dramatically operative findings. This table displays the essence of the
associated with the depth of invasion in fractional thirds model’s results on pelvic lymph node status as a function
than absolute millimeters. The small number of patients of the various combinations of the five significant risk
with positive parametrium and less than deep-third tumor factors. Age was collapsed into only two categories in
invasion made it impossible to estimate their risk of nodal Tables 4 and 5 because its impact on risk of nodal in-
involvement. The positive correlation between deep- volvement was the least dramatic. The breakpoint of 50
third invasion and parametrial invasion was dramatic. was chosen to include enough patients in the older group
Among those patients with negative parametrium, 32% to display frequency of nodal involvement. It does not
had deep-third invasion, in contrast to 86% among pa- represent the optimal breakpoint for differentiation risk.
tients with a positive parametrium. The lowest risk (i.e., 1%) in the upper left corner of
Table 4 gives the percentage probability (based on the Table 5 is associated with negative capillary-lymphatic
model) of a patient having microscopic pelvic lymph spaces and parametrium, superficial cervix invasion, and
node metastasis among patients with no gross intra- histologic grade 1 or 2. The highest risk of nodal me-
318 DELGADO ET AL.

TABLE 4
Percentage Probability (Based on the Logistic Model) of a Patient Having Positive Pelvic Lymph Nodes for Prognostic Factors:
Parametrial Status, Depth of Invasion, Age, Capillary-Lymphatic Spaces, and Grade
Negative capillary-lymphatic spaces Positive capillary-lymphatic spaces
Parametrial status,
depth of invasion, and age Grades 1, 2 Grade 3 Grades 1, 2 Grade 3

Percentage expected
Negative parametrium
Superficial third
51+ 1 8 2 18
5 50 1 12 3 30
Middle third
51+ 4 7 11 19
s 50 8 12 21 30
Deep third
51+ 8 7 24 24
6 50 15 15 35 36
Positive parametrium
Deep third
51+ 22 29 40 36
G 50 34” 34 60 61

a There were only 6 patients with positive parametrium and less than deep-third invasion. There were 13 patients with one or more of the
risk factors unknown: depth of invasion, parametrial and capillary-lymphatic space status.
b The study population had no patients with this combination of the five risk factors. The 34% probability is based on an age of 33 years.

tastasis is 60 to 61% among patients with positive cap-
illary-lymphatic spaces, positive parametrium, deep-
third invasion, and age at diagnosis less than or equal
to 50 years.
Table 5 shows the observed percentages of patients
with positive pelvic lymph nodes relative to the five sig-
nificant risk factors. With few exceptions, the observed
percentages compare well with the corresponding per-
centages predicted by the model (Table 4) when the num-
ber of patients in the category exceeds 10. None of the
30 patients included in the first row of Table 5 (i.e.,
negative parametrium, superficial invasion, and age more

TABLE 5
Percentage of Patients with Positive Pelvic Lymph Nodes by Parametrial Status, Depth of Invasion, Age, Capillary-Lymphatic
Spaces, and Grade
Negative capillary-lymphatic spaces Positive capillary-lymphatic spaces

Grades 1, 2 Grade 3 Grades 1, 2 Grade 3

Parametrial status,
depth of invasion, and age % No. % No. % No. % No.

Negative parametrium
Superficial third
51+ 0 14 0 4 0 11 0 1
s 50 2 84 13 24 2 49 33 9
Middle third
51+ 0 17 0 9 9 11 0 6
s 50 11 70 13 39 18 40 46 13
Deep third
51+ 9 23 0 14 22 23 20 5
s 50 6 36 29 14 37 51 43 21
Positive parametrium
Deep thirdb
51+ 29 7 100 1 29 7 50 4
s 50 - 0 0 1 78 9 44 9

Note. There were 13 patients with one or more of the risk factors unknown: depth of invasion, parametrial status, and capillary-lymphatic
space status.
b There were only 6 patients with positive parametrium and less than deep-third invasion, and these were not included in the table. None
had positive pelvic nodes.
 SQUAMOUS CARCINOMA
than 50 years) had positive pelvic lymph nodes. In con-
trast, of patients with deep-third invasion, positive para-
metrium, and capillary-lymphatic space involvement, 15
(52%) had positive pelvic lymph nodes.
There are only two categories for age at diagnosis in
Tables 4 and 5 because it was the least dramatic of the
significant factors and to keep enough patients in most
of the table cells to have reasonable estimates of the
frequency of positive pelvic nodes. The breakpoint of 50
was chosen to keep a sufficient number of patients in
the older category and it is a point where age begins to
make a notable decrease in risk. The effect on risk of
age at diagnosis can best be demonstrated by example.
Taking the category of negative parametrium, middle-
third invasion, negative capillary-lymphatic spaces, and
grade l/2 tumor, the expected probabilities of nodal in-
volvement for ages 35, 45, 55, and 65 are 9, 8, 5, and
3%, respectively.
DISCUSSION
The original population of patients registered in this
GOG study involved 1125 patients from 33 institutions
reporting to a central statisical office, with the surgical
pathology and other data reviewed by a central com-
mittee. A goal of the study was to identify factors that
could predict prognosis and indicate therapy for patients
with primary carcinoma clinically confined to the cervix
with more than 3 mm invasion. All patients were to
undergo radical hysterectomy, paraaortic and pelvic
lymphadenectomy, and peritoneal cytology; however,
hysterectomy was not required if gross extrauterine dis-
ease (including larged fixed pelvic nodes confirmed by
frozen section) or microscopic aortic node metastases
were found. Of the 940 evaluable patients, the 732 with
squamous carcinoma were analyzed relative to preop-
erative, intraoperative, and postoperative categories to
determine those factors independently associated with
pelvic node metastasis.
An initial comparison was made of the squamous car-
cinoma group meeting all study requirements, no gross
extrauterine disease, and negative aortic nodes with
those having gross disease beyond the uterus and/or
metastases to the aortic nodes. Gross disease beyond
the uterus was independently correlated with GOG per-
formance status, tumor grade, tumor size, and tumor
gross morphology. Tumor gross morphology did not in-
fluence the observed frequency of gross disease beyond
the uterus in the extreme-risk groups. Forty-seven per-
cent of patients in the highest-risk group, (i.e., GOG
performance status 1-2, highest histological grade, max-
imum tumor diameter greater than 3 cm) had gross dis-
ease beyond the uterus; however, 3 (4%) patients in the
lowest-risk group, 2 of whom had occult cancer only,
OF THE CERVIX 319
had gross disease beyond the uterus. The correlations
thus indicate an insufficient specificity and sensitivity to
provide a satisfactory level of confidence for predicting
the presence of gross disease or aortic metastases on
purely preoperative, clinical factors.
In 674 selective aortic node dissections, 33 (5%) had
clinically occult metastatic cancer, 4 (12%) of which were
missed at frozen section. The real percentage of meta-
static aortic nodes in stage I disease cannot be assessed,
because in several patients with disease beyond the cer-
vix, node dissection was not performed. In view of the
limitations of the protocol design, however, definitive
guidelines for aortic node dissection in stage I squamous
cell cancer of the cervix cannot be given.
Pelvic lymph node involvement was found in 15.5%
of patients with disease apparently confined to the uterus
at exploration. Patients with disease beyond the uterus
(including microscopic metastatic aortic nodes) did not
undergo pelvic lymphadenectomy.
Six of 177 (3.4%) patients with 5 mm or less invasion
had pelvic node metastasis, the finding associated with
the lowest risk of nodal disease in the study. Only two
patients had positive pelvic washings, indicating that this
procedure may be of very little value.
This study confirms previous publications that con-
clude that histological grade has a linear correlation with
lymph node involvement and clinical tumor size corre-
lates with the risk of positive pelvic nodes [l]. However,
this study also indicates that patients with occult cancers
can have nodal metastases, and that patients with exo-
phytic lesions have the same risk for nodal metastases
as those with endophytic and ulcerated lesions. Although
more patients had positive pelvic nodes when the uterine
cavity was involved, the difference was not statistically
significant. Capillary-lymphatic space invasion, found in
43% of the cases overall, correlated strongly with the
risk of positive lymph nodes (25% vs 8%).
For patients without gross tumor beyond the uterus
and negative aortic lymph nodes, five risk factors were
associated with pelvic node metastases: depth of inva-
sion (greater than one-third), parametrial involvement,
capillary-lymphatic space invasion, tumor grade, and
gross cervical tumor. Using logistic analysis, four factors
were found to be highly statistically significant and to
operate independently: depth of invasion, capillary-lym-
phatic space invasion, grade, and parametrial extension.
By use of the model, risk groups were identified rang-
ing from a 1 to 61% probability of having positive pelvic
nodes. Of greater interest to the clinician is a model of
pelvic node risk utilizing preoperative data. This was
accomplished with unsatisfactory results. In the low-risk
group, those with grade I and clinically occult tumors,
5% of patients had microscopically positive pelvic nodes.
In contrast, 22% of patients with grade 3 and clinically
320 DELGADO ET AL.
gross tumors had positive nodes. Additional data on re-
currence and survival, after further follow-up, may give
a clearer indication of risk factors permitting more ac-
curate identification of patients with early invasive cerv-
ical cancer who require additional or alternate therapy.
ACKNOWLEDGMENTS
The following are participating institutions and the National Cancer
Institute grants supporting this study: University of Alabama at Bir-
mingham (CA-12484), University of Oregon Health Sciences Center,*
Duke University Medical Center (CA-12534) Hahnemann Medical Col-
lege/Jefferson Medical College/Temple University School of Medicine
(CA-12478), University of Rochester Medical Center (CA-12482), Wal-
ter Reed Army Medical Center (CA-23501), University of Minnesota
Medical School (CA-23088), University of Southern California Medical
Center at Los Angeles (CA-37535), University of Mississippi Medical
Center (CA-13633), Colorado Foundation for Medical Care (CA-15975).
University of California Medical Center at Los Angeles (CA-13630),
University of Miami School of Medicine (CA-37234), Milton S. Hershey
School of Medicine of Pennsylvania State University (CA-16386),
Georgetown University Hospital (CA-16938) University of North Car-
olina School of Medicine (CA-23073), University of Texas Health Sci-
ence Center at Dallas (CA-28160), Indiana University Medical Center
(CA-21720), Bowman Gray School of Medicine of Wake Forest Uni-
versity (CA-21946), The Albany Medical College of Union University,*
University of California Medical Center at Irvine (CA-23765), Tufts
New England Medical Center (CA-37569) Illinois Cancer Council (CA-
27806), University of Pittsburgh School of Medicine,* St. Louis Uni-
versity Medical Center (CA-35571), Stanford University Medical Cen-
ter,* University of Connecticut Medical Center,* State University of
New York-Downstate Medical Center (CA-34477) University of
Michigan Medical School,* Jacksonville University Hospital,* Latter
Day Saints Hospital,* University of Utah Medical Center (CA-15469),
University of Puerto Rico,* and University of Kentucky.* (Partici-
pating institutions followed by an asterisk are unfunded.)
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