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Gynecologic Oncology 125 (2012) 287–291

Contents lists available at SciVerse ScienceDirect

Gynecologic Oncology
journal homepage: www.elsevier.com/locate/ygyno

Prognostic significance of adenocarcinoma histology in women with cervical cancer


Vijaya Galic a, Thomas J. Herzog a, d, Sharyn N. Lewin a, d, Alfred I. Neugut b, c, d, William M. Burke a,
Yu-Shiang Lu a, Dawn L. Hershman b, c, d, Jason D. Wright a, d,⁎
a
Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, United States
b
Department of Medicine, Columbia University College of Physicians and Surgeons, United States
c
Department of Epidemiology, Mailman School of Public Health, United States
d
Herbert Irving Comprehensive Cancer Center, United States

a r t i c l e i n f o a b s t r a c t

Article history: Objectives. We performed a population-based analysis to determine the effect of histology on survival for
Received 29 November 2011 women with invasive cervical cancer.
Accepted 11 January 2012 Methods. The Surveillance, Epidemiology and End Results database was used to identify women with
Available online 18 January 2012 stage IB-IVB cervical cancer treated from 1988 to 2005. Patients were stratified by histology (squamous, ad-
enocarcinoma, and adenosquamous). Clinical characteristics, patterns of care, and outcomes were analyzed
Keywords:
using multivariable logistic regression and Cox proportional hazards models.
Cervical cancer
Cervical carcinoma
Results. A total of 24,562 patients were identified including 18,979 (77%) women with squamous cell car-
Adenocarcinoma cinomas, 4103 (17%) with adencarcinomas, and 1480 (6%) with adenosquamous tumors. Women with ade-
Squamous cell carcinoma nocarcinomas were younger, more often white, and more frequently married than patients with squamous
Histology cell tumors (p b 0.0001 for all). Patients with adenocarcinomas were more likely to present with early-
stage disease (p b 0.0001). At diagnosis, 26.7% of women with adenocarcinomas had stage IB1 tumors com-
pared to 16.9% of those with squamous cell carcinomas. Among women with early-stage (IB1-IIA) tumors,
patients with adenocarcinomas were 39% (HR = 1.39; 95% CI, 1.23–1.56) more likely to die from their tumors
than those with squamous cell carcinomas. For patients with advanced-stage disease (stage IIB-IVA) women
with adenocarcinomas were 21% (HR = 1.21; 95% CI, 1.10–1.32) more likely to die from their tumors than
those with squamous neoplasms. Five-year survival for stage IIIB neoplasms five-year survival was 31.3%
(95% CI, 29.2–33.3%) for squamous tumors vs. 20.3% (95% CI, 14.2–27.1%) for adenocarcinomas.
Conclusion. Cervical adenocarcinomas are more common in younger women and white patients. Adeno-
carcinoma histology negatively impacts survival for both early and advanced-stage carcinomas.
© 2012 Elsevier Inc. All rights reserved.

Introduction Oncology Group (GOG) found no difference in outcome for squamous


cell carcinomas and adenocarcinomas [10]. Many of these studies in-
Approximately 20–25% of cervical carcinoma is comprised of adeno- clude small numbers of patients, are from single institutions, or in-
carcinomas [1]. Unlike squamous cell carcinoma, which has progressive- clude patients treated over long periods of time. Additionally, the
ly declined in incidence, adenocarcinomas have increased [2]. The majority of published studies have focused on early-stage tumors,
increased incidence of adenocarcinomas is likely multifactorial, although data specifically examining women with advanced stage disease has
difficulties in detecting these lesions by cytology and variability in diag- been limited.
nosing the precursor in-situ lesion likely play a substantial role [3–5]. Given the rising incidence of adenocarcinomas the effect of histol-
The effect of tumor histology on outcomes for women with cervi- ogy on outcome is of particular importance. If adenocarcinomas are
cal cancer has been actively debated with conflicting results. While more aggressive than their squamous counterparts histology- specific
some studies have shown that survival for the two histologies is protocols or inclusion of histology as a risk factor in treatment algo-
equivalent, other data has suggested that adenocarcinomas are rithms may be warranted. The goal of our study was to examine the
more aggressive and associated with decreased survival [6–11]. A effect of histology on survival for women with invasive cervical
study of women with stage IB tumors conducted by the Gynecologic cancer.

Materials and methods


⁎ Corresponding author at: Division of Gynecologic Oncology, Department of Obstetrics
and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort
Washington Ave, 8th Floor, New York, NY 10032, United States. Fax: +1 212 305 3412. Data from the National Cancer Institute's Surveillance, Epidemiology,
E-mail address: jw2459@columbia.edu (J.D. Wright). and End Results (SEER) database was analyzed [12]. SEER is a

0090-8258/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.ygyno.2012.01.012
288 V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291

population-based registry that encompasses 17 geographically distinct tumors included higher tumor grade and more advanced stage.
tumor registries and includes approximately 26% of the United States In a Kaplan–Meier analysis of cancer-specific survival for patients
population [13]. with stage IIIB neoplasms, survival of women with adenocarci-
Women diagnosed with stage IB1-IVB invasive cervical cancer nomas was inferior to that of patients with squamous cell tumors
from 1988 to 2005 were analyzed. Patients were classified based (p = 0.014) (Fig. 2).
on their tumor histology into the following groups: squamous, ad- Five-year survival was then examined. For women with stage IB1
enocarcinoma or adenosquamous carcinoma. Demographic data tumors, survival was 88.2% (95% CI, 86.9–89.5%) for squamous le-
collected included age at diagnosis (b40, 40–65, > 65 years), race sions, 84.8% (95% CI, 82.0–87.3%) for adenocarcinomas, and 81.7%
(white, black or other), and marital status (married, single, un- (95% CI, 76.7–85.8%) for adenosquamous cancers (Table 4). For
known). The year of diagnosis was classified as 1988–1993, stage IIIB neoplasms five-year survival was 31.3% (95% CI, 29.2–
1994–1999, or 2000–2005. The geographic residence at the time 33.3%) for squamous tumors, 20.3% (95% CI, 14.2–27.1%) for adeno-
of diagnosis was categorized into one of the following United carcinomas, and 24.6% (95% CI, 15.7–34.5%) for adenosquamous
States regions: east (Connecticut, New Jersey, Atlanta, rural Geor- carcinomas.
gia) central (Detroit, Iowa, Kentucky, Louisiana, Utah), and west
(Alaska, California, Hawaii, Los Angeles, New Mexico, San Fran- Discussion
cisco, San Jose, Seattle). Tumor grade (1, 2, or 3) was recorded
for each patient. Stage was assigned based on the reported SEER Our findings suggest that tumor histology has an important im-
extent of disease codes and American Joint Cancer Committee pact on survival for women with cervical cancer. While a number of
(AJCC) criteria. The primary treatment modality (radiation, surgery prior reports have examined the influence of histology on outcome,
or no treatment) as well as whether lymphadenectomy was per- our analysis specifically explored the influence of adenocarcinoma
formed were also recorded. histology on outcome stratified by stage. For both early and
Frequency distributions for categorical variables were com- advanced-stage disease women with adenocarcinomas had poorer
pared using chi square tests. Cancer specific and overall survival survival.
were analyzed using multivariable Cox proportional hazards For women with early-stage cervical cancer survival is similar fol-
models. Separate models were developed to analyze early-stage lowing radical hysterectomy or primary radiotherapy [14]. While pa-
(IB1-IIA) and advanced-stage (IIB-IVA) patients. All analyses tients treated surgically who have high-risk tumor features (nodal
were performed with SAS version 9.2 (SAS Institute Inc., Cary, involvement, positive margins, parametrial spread) benefit from ad-
North Carolina). juvant therapy, the postoperative management of women with inter-
mediate risk tumors remains controversial [15]. While adjuvant
Results radiation has not been shown to improve survival for women with in-
termediate risk tumors, the recurrence rate in patients with adeno-
A total of 24,562 patients were identified including 18,979 (77.3%) carcinomas and adenosquamous carcinomas decreased from 44% to
women with squamous cell carcinomas, 4103 (16.7%) with adenocar- 9% in a prospective trial of adjuvant radiation. In contrast, the recur-
cinomas, and 1480 (6.0%) with adenosquamous tumors. Table 1 dis- rence rate in squamous tumors decreased from 28% to 20%, suggest-
plays the demographic characteristics of the cohort. At the time of ing that adenocarcinomas as a subset may derive the greatest
diagnosis, women with adenocarcinomas were younger, more often benefit from postoperative radiation [16]. Our findings suggest that
white, and more frequently married than patients with squamous among women with stage IB-IIA with adenocarcinomas have an infe-
cell tumors (p b 0.0001 for all). Women with adenocarcinomas were rior prognosis to women with squamous lesions. Women with early-
more likely to present with early-stage disease (p b 0.0001). At diag- stage adenocarcinomas were nearly 40% more likely to die from their
nosis, 26.7% (n = 1094) of women with adenocarcinomas had stage disease than patients with squamous cell carcinomas. Our findings as
IB1 tumors compared to 16.9% (n = 3214) of those with squamous well as the data from the Gynecologic Oncology Group's study of ad-
cell carcinomas, while 5.8% (n = 238) of those with adenocarcinomas juvant radiotherapy suggest that physicians should take into account
had stage IIIB disease vs. 13.5% (n = 2568) of patients with squamous histology in treatment planning in patients with early-stage disease
lesions. Primary treatment consisted of surgery in 2852 (69.5%) pa- managed surgically.
tients with adenocarcinomas and in 9452 (49.8%) of women with Little data has been reported to examine whether histology has
squamous cell carcinomas (p b 0.0001). an influence on outcome for women with advanced stage disease.
The characteristics of patients with early-stage (IB1-IIA) neo- Curative intent therapy for most women with stage IIB-IVA cervi-
plasms are displayed in Table 2. Compared to women with squamous cal cancer is chemoradiation [17,18]. We noted that even for pa-
cell carcinomas, the multivariable odds ratio for death from cervical tients with advanced stage disease histology had an impact on
cancer was 1.39 (95% CI, 1.23–1.56) for women with adenocarci- survival. Five-year survival for women with stage IIIB squamous
nomas and 1.55 (95% CI, 1.32–1.82) for adenosquamous tumors. Sim- tumors was 31% compared to only 20% for women with adenocar-
ilar trends were noted for overall survival. Other adverse prognostic cinomas. An important consideration is the influence on the addi-
factors for women with early-stage tumors included black race, tion of chemotherapy to radiation for the treatment of advanced
higher tumor grade, treatment with radiation, and higher stage. In a stage disease and how this impacts the influence of histology on
Kaplan-Meier analysis, cancer-specific survival for women with survival. Although SEER lacks data on chemotherapy, we per-
stage IB1 adenocarcinomas and adenosquamous tumors was inferior formed a sensitivity analysis and examined patients treated from
to that of stage matched patients with squamous cell carcinomas 1988 to 1999 (before chemoradiation) as well as those treated
(p = 0.001) (Fig. 1). after the intronduction of chemoradiation (2000–2005). In both
Among women with advanced-stage disease (stage IIB-IVA), subgroups women with adenocarcinomas had an statistically sig-
histology continued to have an effect on survival (Table 3). The nificantly lower survival even after adjustment for other demo-
multivariable odds ratio for cancer-specific survival for women graphic and treatment characteristics. These findings suggest that
with adenocarcinomas was 1.21 (95% CI, 1.10–1.32) and 1.03 advanced stage cervical adenocarcinomas are inherently more ag-
(95% CI, 0.91–1.18) for adenosquamous carcinomas. Overall sur- gressive than squamous cell tumors.
vival was also lower for patients with adenocarcinomas We also explored the outcomes of women with adenosquamous
(OR = 1.22; 95% CI, 1.13–1.33). Other factors associated with de- tumors. Prior studies have reported have reported inferior outcomes
creased cancer-specific survival for women with stage IIB-IVA for women with adenosquamous tumors [10,19]. In a prospective
V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291 289

Table 1
Association between tumor histology and demographic and clinical characteristics.

Squamous cell (n = 18,979) Adenocarcinoma Adenosquamous (n = 1480)


(n = 4103)

N (%) N (%) N (%) p-value

Age at diagnosis b 0.0001


b40 4575 (24.1) 1091 (26.6) 447 (30.2)
40–65 10,151 (53.5) 2168 (52.8) 786 (53.1)
>65 4253 (22.4) 844 (20.6) 247 (16.7)
Race b 0.0001
White 14,012 (73.8) 3278 (79.9) 1165 (78.7)
Black 2912 (15.3) 312 (7.6) 149 (10.1)
Other 1975 (10.4) 487 (11.9) 163 (11.0)
Unknown 80 (0.4) 26 (0.6) 3 (0.2)
Year of diagnosis 0.0001
1988–1993 4261 (22.5) 829 (20.2) 326 (22.0)
1994–1999 5237 (27.6) 1109 (27.0) 458 (31.0)
2000–2005 9481 (50.0) 2165 (52.8) 696 (47.0)
SEER registry b 0.0001
West 10,506 (55.4) 2369 (57.7) 904 (61.1)
Central 4828 (25.4) 961 (23.4) 304 (20.5)
East 3645 (19.2) 773 (18.8) 272 (18.4)
Marital status b 0.0001
Married 7958 (41.9) 2166 (52.8) 721 (48.7)
Single 10,240 (54.0) 1768 (43.1) 720 (48.7)
Unknown 781 (4.1) 169 (4.1) 39 (2.6)
Tumor grade b 0.0001
1 775 (4.1) 951 (23.2) 43 (2.9)
2 6111 (32.2) 1350 (32.9) 306 (20.7)
3 7223 (38.1) 1008 (24.6) 822 (55.5)
Unknown 4870 (25.7) 794 (19.4) 309 (20.0)
Primary treatment b 0.0001
Surgery 9452 (49.8) 2852 (69.5) 994 (67.2)
Radiation 8480 (44.7) 1020 (24.9) 422 (28.5)
No treatment 1047 (5.5) 231 (5.6) 64 (4.3)
Lymphadenectomy b 0.0001
Yes 7149 (37.7) 2182 (53.2) 843 (57.0)
No 11,830 (62.3) 1921 (46.8) 637 (43.0)
Stage b 0.0001
IB1 3214 (16.9) 1094 (26.7) 383 (25.9)
IB2 1701 (9.0) 343 (8.4) 168 (11.4)
IB NOS 3978 (21.0) 1359 (33.1) 331 (22.4)
IIA 1488 (7.8) 202 (4.9) 84 (5.7)
IIB 3754 (19.8) 424 (10.3) 236 (16.0)
IIIA 695 (3.7) 80 (2.0) 25 (1.7)
IIIB 2568 (13.5) 238 (5.8) 111 (7.5)
IVA 622 (3.3) 82 (2.0) 30 (2.0)
IVB 959 (5.1) 281 (6.9) 112 (7.6)

GOG study of patients with IB1 cervical cancer treated with radical NOGOR in adenocarcinomas but not squamous carcinomas [22]. Final-
hysterectomy, overall survival was worse for adenosquamous carci- ly, adenocarcinomas may differ from squamous carcinomas with re-
noma than for other histologies [10]. A similar observation was spect to the role of human papillomavirus (HPV). While a causal
made in a more recent retrospective study, which included IB1 cervix relationship has been established between both HPV 16 and 18 infec-
cancer patients stratified according to surgicopathological risk factors. tion and subsequent development of cervical adenocarcinoma, HPV
In otherwise low risk patients with IB1 tumors, patients with adenos- 18 infection is more common in adenocarcinomas than squamous
quamous histology were more likely to have a poorly differentiated carcinomas [23,24].
tumor and both shorter disease free survival and overall survival While our study benefits from the inclusion of a large number
rates compared to patients without adenocarcinomas [19]. Our find- of subjects, we recognize a number of important limitations. Like
ings were notable in that while survival for early-stage adenosqua- all administrative datasets, central pathology review is not per-
mous tumors was inferior to that of squamous cells carcinomas, formed for patients registered in SEER. While we limited our
survival was similar for the two histologies in women with advanced study to the most common histologic variants of cervical cancer,
stage disease. we cannot exclude the possibility that some patients were mis-
There is considerable evidence to suggest that the molecular classified. SEER lacks data on some important pathologic parame-
mechanisms underlying the pathogenesis of adenocarcinomas and ters including lymphovascular space invasion, margin status, and
squamous carcinomas are distinct. A gene expression array analysis parametrial spread that may have provided additional insight
has shown that adenocarcinomas may be reliably distinguished into the findings we noted. Finally, SEER lacks data on timing
from squamous cell carcinomas based on their expression signature and distribution of recurrences. As such, our study was limited
[20,21]. Notably, the algorithm devised by Hall and colleagues for cer- to analyzing cancer-specific survival.
vical cancer correctly classified a set of lung squamous and adenocar- Our findings support the hypothesis that adenocarcinomas are a
cinomas, suggesting that gene expression profiles may affect behavior distinct clinical entity from squamous cell carcinomas. There are sev-
more so than tissue of origin [21]. Methylation studies have demon- eral possible explanations for the inferior outcomes of both early and
strated hypermethylation of growth-inhibitory genes such as advanced stage adenocarcinomas. It has been previously argued that
290 V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291

Table 2 Table 3
Survival for patients with stage IB1-IIA cervical cancer. Survival for stage IIB-IVB cervical cancer.

Cancer-specific survival Overall survival Cancer-specific survival Overall survival


N (%) N (%)

Histology Histology
Squamous cell 10,381 (72.4) Referent Referent Squamous cell 8598 (84.2) Referent Referent
Adenocarcinoma 2998 (20.9) 1.39 (1.23–1.56) 1.16 (1.05–1.27) Adenocarcinoma 1105 (10.8) 1.21 (1.10–1.32) 1.22 (1.13–1.33)
Adenosquamous 966 (6.7) 1.55 (1.32–1.82) 1.36 (1.19–1.55) Adenosquamous 514 (5.0) 1.03 (0.91–1.18) 1.02 (0.91–1.15)
Age at diagnosis Age at diagnosis
b40 4581 (31.9) Referent Referent b40 1532 (15.0) Referent Referent
40–65 7316 (51.0) 1.04 (0.93–1.15) 1.40 (1.28–1.54) 40–65 5789 (56.7) 0.94 (0.86–1.02) 1.02 (0.94–1.10)
>65 2448 (17.1) 1.42 (1.25–1.62) 3.17 (2.87–3.51) >65 2896 (28.3) 1.10 (1.00–1.20) 1.49 (1.37–1.62)
Race Race
White 10,970 (76.5) Referent Referent White 7485 (73.3) Referent Referent
Black 1764 (12.3) 1.36 (1.20–1.54) 1.33 (1.21–1.45) Black 1609 (15.7) 1.17 (1.08–1.27) 1.17 (1.10–1.26)
Other 1518 (10.6) 0.98 (0.85–1.14) 0.85 (0.76–0.96) Other 1107 (10.8) 0.81 (0.73–0.90) 0.80 (0.73–0.88)
Unknown 93 (0.7) 0.21 (0.05–0.83) 0.34 (0.15–0.76) Unknown 16 (0.2) 1.86 (0.97–3.58) 1.57 (0.84–2.91)
Year of diagnosis Year of diagnosis
1988–1993 3343 (23.3) Referent Referent 1988–1993 2073 (20.3) Referent Referent
1994–1999 4105 (28.6) 0.85 (0.76–0.95) 0.94 (0.86–1.02) 1994–1999 2699 (26.4) 0.92 (0.86–1.00) 0.91 (0.85–0.98)
2000–2005 6897 (48.1) 0.89 (0.80–1.00) 0.96 (0.87–1.05) 2000–2005 5445 (53.3) 0.82 (0.76–0.89) 0.83 (0.78–0.88)
SEER registry SEER registry
West 8134 (56.7) Referent Referent West 5645 (55.3) Referent Referent
Central 3543 (24.7) 1.08 (0.97–1.20) 1.07 (0.98–1.16) Central 2550 (25.0) 1.06 (0.99–1.14) 1.07 (1.01–1.14)
East 2668 (18.6) 1.00 (0.89–1.13) 0.99 (0.90–1.09) East 2022 (19.8) 0.98 (0.91–1.07) 0.97 (0.91–1.04)
Marital status Marital status
Married 6990 (48.7) Referent Referent Married 3855 (37.7) Referent Referent
Single 6736 (47.0) 1.07 (0.98–1.18) 1.25 (1.16–1.34) Single 5992 (58.6) 1.09 (1.02–1.16) 1.13 (1.07–1.20)
Unknown 619 (4.3) 0.82 (0.64–1.05) 0.96 (0.80–1.15) Unknown 370 (3.6) 1.18 (1.01–1.38) 1.15 (1.00–1.32)
Tumor grade Tumor grade
1 1280 (8.9) Referent Referent 1 489 (4.8) Referent Referent
2 4724 (32.9) 1.80 (1.44–2.24) 1.38 (1.18–1.62) 2 3043 (29.8) 1.11 (0.96–1.29) 1.11 (0.97–1.27)
3 4981 (34.7) 2.47 (1.98–3.09) 1.77 (1.52–2.08) 3 4072 (39.9) 1.38 (1.20–1.60) 1.36 (1.19–1.55)
Unknown 3360 (23.4) 1.35 (1.07–1.70) 1.24 (1.06–1.46) Unknown 2613 (25.6) 1.11 (0.95–1.30) 1.15 (1.00–1.31)
Primary treatment Primary treatment
Surgery 10,665 (74.4) Referent Referent Treatment 9370 (91.7) Referent Referent
Radiation 3185 (22.2) 2.24 (2.03–2.49) 2.07 (1.91–2.23) No treatment 847 (8.3) 2.51 (2.29–2.76) 2.53 (2.33–2.75)
No treatment 495 (3.5) 3.54 (2.89–4.36) 3.82 (3.31–4.40) Stage
Stage IIB 4414 (43.2) Referent Referent
IB1 4691 (32.7) Referent Referent IIIA 800 (7.8) 2.06 (1.84–2.31) 1.85 (1.67–2.04)
IB2 2212 (15.4) 2.08 (1.80–2.40) 1.87 (1.67–2.10) IIIB 2917 (28.6) 2.26 (2.10–2.44) 2.04 (1.91–2.18)
IB NOS 5668 (39.5) 1.26 (1.10–1.43) 1.29 (1.17–1.43) IVA 734 (7.2) 3.51 (3.14–3.91) 3.12 (2.84–3.44)
IIA 1774 (12.4) 2.66 (2.30–3.09) 2.07 (1.84–2.32) IVB 1352 (13.2) 4.87 (4.46–5.32) 4.10 (3.79–4.44)

adenocarcinomas tend to be diagnosed at a later stage, presumably adenocarcinomas [25]. In sum, this data would suggests that adeno-
because screening is less effective. The present study, however, con- carcinomas and squamous carcinomas are fundamentally different
trolled for this by analyzing survival controlling for stage. The second on a molecular level. Further prospective studies to confirm the pre-
hypothesis is that adenocarcinomas are more likely to metastasize to sent findings in both early and late stage adenocarcinomas would
the regional nodes than squamous carcinomas. This too is less likely be of great value. While current screening and management guide-
given that the rate of pelvic lymph node metastasis following radical lines do not take histology into account, recognizing that adenocarci-
hysterectomy in early stage disease is similar between squamous and nomas may be distinct may provide an opportunity for improving

Fig. 1. Kaplan–Meier analysis of cancer-specific survival for women with stage IB1 cervical Fig. 2. Kaplan–Meier analysis of cancer-specific survival for women with stage IIIB cervical
cancer (p= 0.001). Solid line-squamous cell carcinoma, dashed line-adenocarcinoma, cancer (p= 0.014). Solid line-squamous cell carcinoma, dashed line-adenocarcinoma,
short-dashed line adenosquamous carcinoma. short-dashed line adenosquamous carcinoma.
V. Galic et al. / Gynecologic Oncology 125 (2012) 287–291 291

Table 4 [10] Look KY, Brunetto VL, Clarke-Pearson DL, et al. An analysis of cell type in patients
Five-year survival stratified by stage. with surgically staged stage IB carcinoma of the cervix: a Gynecologic Oncology
Group study. Gynecol Oncol 1996;63:304–11.
Squamous Adenocarcinoma Adenosquamous [11] Webb JC, Key CR, Qualls CR, Smith HO. Population-based study of microinvasive
adenocarcinoma of the uterine cervix. Obstet Gynecol 2001;97:701–6.
IB1 88.2% (86.9–89.5%) 84.8% (82.0–87.3%) 81.7% (76.7–85.8%) [12] Surveillance, Epidemiology, and End Results, SEER*Stat Database: Incidence-
IB2 69.0% (66.3–71.4%) 68.3% (62.0–73.8%) 65.1% (56.4–72.6%) SEER 9 Regs Limited-Use, Nov 2006 Sub (1973–2004), National Cancer Institute,
IBNOS 77.9% (76.4–79.2%) 83.7% (81.4–85.8%) 77.5% (72.2–81.8%) DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April
IIA 58.3% (55.3–61.1%) 45.5% (37.3–53.3%) 42.0% (29.5–54.0%) 2007, based on the November 2006 submission. http://.seer.cancer.gov.
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IIIA 33.7% (29.7–37.8%) 15.6% (7.8–25.8%) 33.8% (12.4–56.9%) [13] The Surveillance, Epidemiology, and End Results (SEER) Program, Data Quality.
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IVB 5.9% (4.4–7.7%) 9.4% (6.0–13.7%) 8.7% (4.0–15.8%) [14] Landoni F, Maneo A, Colombo A, et al. Randomised study of radical surgery versus
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