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Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NYHerbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NYHerbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NYHerbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NYHerbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NYHerbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
Reprints: Jason D. Wright, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, 161 Fort Washington Ave., Eighth Flr., New York, NY. 10032
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NYHerbert Irving Comprehensive Cancer Center, Columbia University, New York, NY
We analyzed the effect of lymphadenectomy on the use of adjuvant radiation treatment for women with stage I-II endometrial cancer.
Study Design
Women with stage I-II endometrioid adenocarcinomas treated between 1988 and 2006 and recorded in the Surveillance, Epidemiology, and End Results database were identified. The influence of lymphadenectomy (LND) on receipt of external beam radiation and brachytherapy stratified was examined.
Results
We identified 58,776 women including 26,043 who underwent LND (44.3%). Among women younger than 60 years of age with stage IA (grades 1, 2, and 3) tumors, LND had no impact on the use of radiation. Patients with stage IB (grade 2 or 3) and stage IC (grade 1 or 2) tumors who underwent lymph node dissection were less likely to undergo external beam radiation and more likely to receive vaginal brachytherapy (P < .05 for all). Furthermore, the extent of lymphadenectomy influenced the receipt of radiation.
Conclusion
Women who undergo lymphadenectomy are less likely to receive whole pelvic radiotherapy.
Endometrial cancer is the most common gynecologic malignancy. In the United States, it is estimated that 43,470 women will be diagnosed with the endometrial cancer in 2010 and that 7950 will die from the disease.
Although the majority of women are diagnosed at an early stage and have a favorable outcome, a number of clinicopathologic risk factors predispose to a poorer prognosis. Age, stage, tumor grade, histologic type, depth of myometrial invasion, and metastasis to the regional lymph nodes are all established prognostic factors.
Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study.
Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study.
The Gynecologic Oncology Group (GOG) demonstrated the importance of nodal metastasis in a landmark surgicopathology study of 621 patients with clinical stage I tumors. In this report the investigators noted that regional lymph nodes were the most common site of extrauterine disease and that the frequency of nodal dissemination correlated with tumor grade and depth of myometrial invasion. Five year recurrence-free survival for patients with pelvic nodal involvement was 58% and decreased to 41% for women with paraaortic metastases.
Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study.
The importance of nodal disease was further acknowledged in 1988 when a surgical staging system that included pathologic assessment of the regional nodes was adopted.
With the recognition of the importance of the status of the regional lymphatics, lymphadenectomy was incorporated into the primary surgical management of women with endometrial cancer.
As the use of lymphadenectomy increased, data emerged that the procedure may provide a therapeutic benefit in and of itself; those patients who underwent a more extensive dissection had improved survival.
However, 2 recent randomized trials cast doubt on the role of nodal dissection. Both of these studies found that lymphadenectomy had no effect on survival and that the procedure was associated with a small, but statistically significant, increase in morbidity.
Although it appears that lymphadenectomy does not directly influence survival, the procedure may be important in guiding adjuvant treatment planning. Although small institutional studies have suggested that nodal dissection effects the allocation of adjuvant treatment, the population-based effect of lymphadenectomy on influencing patterns of care remains unknown.
Even if lymphadenectomy does not alter survival, the procedure may be worthwhile in subsets of patients if it can spare women unnecessary additional treatment. Surgically staged patients may avoid adjuvant radiation altogether or opt for brachytherapy, which is associated with survival that is comparable with whole pelvic radiation.
The goal of our study was to perform a population-based analysis to determine the effect of lymphadenectomy on influencing the use of adjuvant radiation treatment for women with stage I-II endometrial cancer.
Materials and Methods
Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was utilized. SEER is a population-based tumor registry that captures data on approximately 26% of the US population.
Surveillance, Epidemiology, and End Results, SEER*Stat Database: incidence-SEER 9 regs limited-use, Nov 2006 Sub (1973-2004), National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2007, based on the November 2006 submission.
All data were publicly available, deidentified, and exempt from institutional review board review.
Women with stage I-II endometrioid adenocarcinomas of the uterine corpus treated between 1988 and 2006 were included in the analysis. The clinical and pathologic date including age at diagnosis (<60 or ≥60 years old), tumor grade (1, 2, or 3), and marital status were collected. The year of diagnosis was classified as 1988-1994, 1995-2000, or 2001-2006.
Patients were categorized based on the geographic area of residence at the time of diagnosis: central (Detroit, MI; Iowa; Kentucky; Louisiana; Utah), eastern (Connecticut; New Jersey; Atlanta, GA; rural Georgia), and western (Alaska; California; Hawaii; Los Angeles, CA; New Mexico; San Francisco, CA; San Jose, CA; Seattle, WA) United States.
Use of adjuvant radiation therapy (external beam or brachytherapy) was collected. Patients who received both external beam and vaginal brachytherapy were included in the external beam radiation group.
Patients who had any lymph nodes removed were classified as having undergone lymphadenectomy. To assess the effect of the extent of lymphadenectomy on the use of adjuvant therapy, a second analysis was performed among women who underwent lymphadenectomy comparing those with 1-9 nodes removed with those who had 10 or more nodes removed.
Staging information was determined for each patient using the extent of disease codes and was based on the 1988 International Federation of Gynecology and Obstetrics (FIGO) staging system.
Clinical and demographic characteristics of the cohort were compared based on the performance of lymphadenectomy and compared using the χ2 test. Use of external beam and vaginal brachytherapy was then compared based on the performance of lymphadenectomy. These analyses were stratified by stage, grade, and age at diagnosis. P < .05 was considered statistically significant. All analyses were performed with SAS version 9.2 (SAS Institute Inc, Cary, NC).
Results
A total of 58,776 women including 26,043 who underwent lymph node sampling (44.3%) and 32,733 who did not undergo lymphadenectomy (55.7%) were identified. The clinical and demographic characteristics of the cohort are displayed in Table 1. Patients who underwent lymphadenectomy were more often nonwhite, were diagnosed from 2001 to 2006, and resided in the western United States (P < .0001 for all). Women with high-grade tumors and patients with more advanced-stage disease were also more likely to undergo lymphadenectomy (P < .0001 for both).
TABLE 1Clinical and demographic characteristics of the cohort
Characteristic
No lymphadenectomy
Lymphadenectomy
P value
32,733 (55.7)
26,043 (44.3)
Age, y
.16
<60
13,718 (41.9)
10,766 (41.3)
≥60
19,015 (58.1)
15,277 (58.7)
Race
< .0001
White
29,371 (89.7)
22,707 (87.2)
Black
1243 (3.8)
1251 (4.8)
Other
2007 (6.1)
1980 (7.6)
Unknown
112 (0.3)
105 (0.4)
Year of diagnosis
< .0001
1988-1994
8572 (26.2)
3451 (13.3)
1995-2000
10,032 (30.7)
6631 (25.5)
2001-2006
14,129 (43.2)
15,961 (61.3)
SEER registry
< .0001
West
16,530 (50.5)
14,134 (54.3)
Central
9352 (28.6)
6199 (23.8)
East
6851 (20.9)
5710 (21.9)
Marital status
.47
Married
18,125 (55.4)
14,387 (55.2)
Single
13,540 (41.4)
10,848 (41.7)
Unknown
1068 (3.3)
808 (3.1)
Tumor grade
< .0001
1
19,347 (59.1)
9695 (37.2)
2
9609 (29.4)
10,124 (38.9)
3
2187 (6.7)
4880 (18.7)
Unknown
1590 (4.9)
1344 (5.2)
Radiation
< .0001
External beam
3727 (11.4)
4598 (17.7)
Brachytherapy
875 (2.7)
1954 (7.5)
Other
165 (0.5)
222 (0.9)
None
27,966 (85.4)
19,269 (74.0)
Stage
< .0001
IA
12,129 (37.1)
6042 (23.2)
IB
16,127 (49.3)
13,006 (49.9)
IC
3447 (10.5)
4898 (18.8)
IIA
570 (1.7)
1008 (3.9)
IIB
460 (1.4)
1089 (4.2)
SEER, Surveillance, Epidemiology, and End Results.
Sharma. Lymphadenectomy for endometrial cancer. Am J Obstet Gynecol 2011.
Table 2 displays the use of radiation (external beam and vaginal brachytherapy) in women younger than 60 years of age stratified by stage and grade. Among the women with stage IA tumors (grades 1, 2, and 3), lymph node dissection had no impact on the use of radiation. Patients with stage IB tumors (grade 2 or 3) who underwent lymph node dissection were less likely to undergo external beam radiation and were more likely to receive vaginal brachytherapy (Figure). For example, among the women with stage IB grade 3 tumors, external beam radiation was administered to 30.0% of those who underwent lymphadenectomy compared with 36.5% of those who did not undergo lymphadenectomy (P = .04), whereas brachytherapy was given to 13.8% of those who underwent nodal dissection and to 4.5% of those who did not (P < .0001).
TABLE 2Effect of lymphadenectomy on use of radiation in women younger than 60 years of age
Variable
Total
Lymph nodes
No lymph nodes
External beam radiation
Vaginal brachytherapy
Lymph node dissection, n (%)
No lymph node dissection, n (%)
P value
Lymph node dissection, n (%)
No lymph node dissection, n (%)
P value
IA
All IA
9861
3316
6545
75 (2.3)
68 (1.0)
< .0001
52 (1.6)
53 (0.8)
.0005
Grade 1
6596
1849
4747
17 (0.9)
31 (0.7)
.25
15 (0.8)
29 (0.6)
.37
Grade 2
2231
978
1253
27 (2.8)
23 (1.8)
.14
15 (1.5)
15 (1.2)
.49
Grade 3
414
279
135
27 (9.7)
10 (7.4)
.45
13 (4.7)
2 (1.5)
.10
IB
All IB
11,606
5415
6191
574 (10.6)
457 (7.4)
< .0001
397 (7.3)
217 (3.5)
< .0001
Grade 1
6064
2179
3885
89 (4.1)
135 (3.5)
.23
78 (3.6)
95 (2.5)
.01
Grade 2
3842
2084
1758
183 (8.9)
200 (11.4)
.008
164 (7.9)
100 (5.7)
.008
Grade 3
1177
889
288
267 (30.0)
105 (36.5)
.04
123 (13.8)
13 (4.5)
< .0001
IC
All IC
1691
1107
584
469 (42.4)
311 (53.3)
< .0001
130 (11.7)
24 (4.1)
< .0001
Grade 1
578
320
258
87 (27.2)
116 (45.0)
< .0001
42 (13.1)
16 (6.2)
.006
Grade 2
650
438
212
177 (40.4)
129 (60.9)
< .0001
46 (10.5)
4 (1.9)
.0001
Grade 3
388
297
91
192 (64.7)
61 (67.0)
.68
21 (7.1)
3 (3.3)
.19
IIA
All IIA
666
428
238
153 (35.8)
99 (41.6)
.14
83 (19.4)
20 (8.4)
.0002
Grade 1
290
162
128
42 (25.9)
43 (33.6)
.15
31 (19.1)
13 (10.2)
.03
Grade 2
258
168
90
68 (40.5)
45 (50.0)
.14
33 (19.6)
6 (6.7)
.006
Grade 3
79
66
13
32 (48.5)
9 (69.2)
.17
9 (13.6)
0 (—)
.16
IIB
All IIB
660
500
160
282 (56.4)
103 (64.4)
.07
53 (10.6)
13 (8.1)
.36
Grade 1
203
136
67
62 (45.6)
38 (56.7)
.14
21 (15.4)
4 (6.0)
.05
Grade 2
282
212
70
121 (57.1)
48 (68.6)
.09
24 (11.3)
9 (12.9)
.73
Grade 3
136
120
16
79 (65.8)
13 (81.3)
.22
7 (5.8)
0 (—)
.32
Total number of patients for each substage includes patients with unknown tumor grade.
Sharma. Lymphadenectomy for endometrial cancer. Am J Obstet Gynecol 2011.
A, Use of external beam radiation in women younger than 60 years of age with stage IB or IC tumors stratified by performance of lymphadenectomy. B, Use of external beam radiation in women 60 years of age or older. C, Use of vaginal brachytherapy in women younger than 60 years of age. D, Use of vaginal brachytherapy in women 60 years of age or older. Solid blue line represents women who underwent lymphadenectomy, dashed red line represents women who did not undergo nodal dissection.
Sharma. Lymphadenectomy for endometrial cancer. Am J Obstet Gynecol 2011.
Similar trends were noted for women with stage IC (grade 1 and 2) tumors. Among those with stage IC grade 2 neoplasms, 40.4% of women who had a lymph node dissection received external beam radiotherapy vs 60.9% of those who did not (P < .0001). In addition, 10.5% of those who underwent lymph node dissection received vaginal brachytherapy compared with 1.9% with no lymph node dissection (P = .0001).
These findings were similar for patients 60 years of age or older (Table 3). Patients with stage IA (grade 3), stage IB (grade 2), stage IC (grades 1 and 2), and stage IIA (grade 2) tumors were less likely to receive pelvic radiotherapy if they underwent lymphadenectomy (P < .05 for all). Patients with stage IB (all grades), stage IC (all grades), and stage IIA (grade 2) who underwent lymphadenectomy were more likely to receive adjuvant vaginal brachytherapy than those who did not undergo lymphadenectomy.
TABLE 3Effect of lymphadenectomy on use of radiation in women 60 years of age or older
Variable
Total
Lymph nodes
No lymph nodes
External beam radiation
Vaginal brachytherapy
Lymph node dissection, n (%)
No lymph node dissection, n (%)
P value
Lymph node dissection, n (%)
No lymph node dissection, n (%)
P value
IA
All IA
8310
2726
5584
102 (3.7)
141 (2.5)
.002
52 (1.9)
67 (1.2)
.01
Grade 1
4860
1196
3664
25 (2.1)
43 (1.2)
.02
6 (0.5)
31 (0.9)
.23
Grade 2
2225
912
1313
36 (4.0)
52 (4.0)
.99
20 (2.2)
19 (1.5)
.19
Grade 3
727
454
273
32 (7.1)
35 (12.8)
.009
19 (4.2)
13 (4.8)
.71
IB
All IB
17,527
7591
9936
890 (11.7)
857 (8.6)
< .0001
578 (7.6)
337 (3.4)
< .0001
Grade 1
7916
2572
5344
120 (4.7)
187 (3.5)
.01
89 (3.5)
127 (2.4)
.006
Grade 2
6628
3188
3440
294 (9.2)
392 (11.4)
.004
250 (7.8)
157 (4.6)
< .0001
Grade 3
2242
1485
757
429 (28.9)
237 (31.3)
.24
183 (12.3)
32 (4.2)
< .0001
IC
All IC
6654
3791
2863
1551 (40.9)
1409 (49.2)
< .0001
423 (11.2)
92 (3.2)
< .0001
Grade 1
2029
990
1039
290 (29.3)
461 (44.4)
< .0001
103 (10.4)
37 (3.6)
.0001
Grade 2
2895
1659
1236
693 (41.8)
646 (52.3)
< .0001
184 (11.1)
36 (2.9)
< .0001
Grade 3
1452
981
471
515 (52.5)
254 (53.9)
.61
90 (9.2)
13 (2.8)
< .0001
IIA
All IIA
912
580
332
187 (32.2)
131 (39.5)
.03
117 (20.2)
37 (11.1)
.0005
Grade 1
285
161
124
35 (21.7)
36 (29.0)
.16
34 (21.1)
18 (14.5)
.15
Grade 2
367
242
125
76 (31.4)
52 (41.6)
.05
55 (22.7)
13 (10.4)
.004
Grade 3
210
140
70
70 (50.0)
36 (51.4)
.85
15 (10.7)
5 (7.1)
.41
IIB
All IIB
889
315
151
315 (53.5)
151 (50.3)
.37
69 (11.7)
15 (5.0)
.001
Grade 1
221
130
91
68 (52.3)
50 (55.0)
.70
17 (13.1)
6 (6.6)
.12
Grade 2
355
243
112
120 (49.4)
63 (56.3)
.23
27 (11.1)
6 (5.4)
.08
Grade 3
242
169
73
97 (57.4)
29 (39.7)
.01
18 (10.7)
1 (1.4)
.01
Total number of patients for each substage includes patients with unknown tumor grade.
Sharma. Lymphadenectomy for endometrial cancer. Am J Obstet Gynecol 2011.
The influence of extent of lymphadenectomy on the use of radiation was then examined (Tables 4 and 5). Patients who underwent lymphadenectomy were stratified based on the number of nodes removed (1-9 vs ≥10 nodes). Patients younger than 60 years of age with stage IB (grades 2 and 3), IC (all grades), IIA (grade 1), and IIB (grade 2) tumors who underwent a more extensive lymphadenectomy (10 or more nodes) were less likely to receive external beam radiation and more likely to receive vaginal brachytherapy than those patients who underwent less extensive nodal sampling (1-9 nodes) (P < .05 for all). For example, among women with stage IC grade 2 neoplasms, 54.8% of women who had 1-9 nodes removed received pelvic radiation compared with 31.0% of those who had 10 or more nodes removed (P < .0001). Similar trends were noted when the extent of lymphadenectomy was examined in patients 60 years of age or older.
TABLE 4Effect of extent of lymphadenectomy (1-9 vs ≥10 nodes) on use of radiation in women younger than 60 years of age who underwent nodal evaluation
Variable
Total
1-9 lymph nodes
≥10 lymph nodes
External beam radiation
Vaginal brachytherapy
1-9 nodes, n (%)
≥10 nodes, n (%)
P value
1-9 nodes, n (%)
≥10 nodes, n (%)
P value
IA
All IA
2998
1351
1647
30 (2.2)
33 (2.0)
.68
21 (1.6)
28 (1.7)
.75
Grade 1
1682
806
876
6 (0.7)
6 (0.7)
.88
8 (1.0)
6 (0.7)
.49
Grade 2
876
375
501
12 (3.2)
13 (2.6)
.59
5 (1.3)
8 (1.6)
.75
Grade 3
242
95
147
11 (11.6)
11 (7.5)
.28
5 (5.3)
8 (5.4)
.95
IB
All IB
4947
2101
2846
259 (12.3)
264 (9.3)
.0006
128 (6.1)
247 (8.7)
.0007
Grade 1
2008
931
1077
43 (4.6)
39 (3.6)
.26
31 (3.3)
45 (4.2)
.32
Grade 2
1894
781
1113
89 (11.4)
78 (7.0)
.0009
55 (7.0)
99 (8.9)
.15
Grade 3
801
303
498
117 (38.6)
123 (24.7)
< .0001
34 (11.2)
80 (16.1)
.06
IC
All IC
1016
393
623
212 (53.9)
212 (34.0)
< .0001
32 (8.1)
94 (15.1)
.001
Grade 1
297
124
173
47 (37.9)
29 (16.8)
< .0001
13 (10.5)
28 (16.2)
.16
Grade 2
402
157
245
86 (54.8)
76 (31.0)
< .0001
11 (7.0)
33 (13.5)
.04
Grade 3
268
99
169
74 (74.8)
101 (59.8)
.01
5 (5.1)
15 (8.9)
.25
IIA
All IIA
401
131
270
55 (42.0)
87 (32.2)
.06
20 (15.3)
59 (22.9)
.12
Grade 1
149
51
98
20 (39.2)
20 (20.4)
.01
9 (17.7)
20 (20.4)
.69
Grade 2
161
53
108
23 (43.4)
40 (37.0)
.44
7 (13.2)
26 (24.1)
.11
Grade 3
59
18
41
9 (50.0)
19 (46.3)
.80
1 (5.6)
6 (14.6)
.32
IIB
All IIB
465
145
320
94 (64.8)
165 (51.6)
.008
8 (5.5)
42 (13.1)
.01
Grade 1
130
37
93
19 (51.4)
42 (45.2)
.52
3 (8.1)
17 (18.3)
.15
Grade 2
196
66
130
46 (69.7)
62 (47.7)
.003
3 (4.6)
19 (14.6)
.03
Grade 3
108
32
76
22 (68.8)
49 (64.5)
.67
2 (6.3)
5 (6.6)
.95
Total number of patients for each substage includes patients with unknown tumor grade.
Sharma. Lymphadenectomy for endometrial cancer. Am J Obstet Gynecol 2011.
The role of lymphadenectomy in endometrial cancer is rapidly evolving. Randomized trials of lymphadenectomy have failed to show a survival advantage for the procedure and have not convincingly demonstrated that lymphadenectomy influences adjuvant treatment planning.
Our population-based analysis of patients treated across the United States clearly demonstrates that the performance of lymphadenectomy effects the allocation of adjuvant treatment. The effects appear to be the most pronounced for women with intermediate risk tumors and suggest that those women who undergo lymphadenectomy are less likely to receive external beam radiation.
The difficulty in extrapolating the role of lymphadenectomy is due in large part to the fact that the optimal adjuvant treatment for most women with endometrial cancer is unknown. Among patients with tumors confined to the uterine corpus, radiation improves local control without having an impact on overall survival.
Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.
PORTEC Study Group Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial Post Operative Radiation Therapy in Endometrial Carcinoma.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.
Evidence-based guidelines for the treatment of women with corpus-confined disease endorse a variety of possible treatments from observation to radiation in combination with chemotherapy.
Among women with nodal disease, controversy also exists with regard to optimal management. Although chemotherapy has been shown to be superior to radiation, a substantial number of women in the United States are treated with a combination of chemotherapy and radiation.
Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study.
Given the uncertain role of radiation in women with cancer confined to the uterus, the most important rationale for pelvic radiation in women with unstaged endometrial cancer is for the treatment of occult nodal disease.
Although it is widely hypothesized that lymphadenectomy influences adjuvant treatment planning, there are relatively few data describing how nodal sampling has an impact on the allocation of treatment.
examined the effect of increased use of surgical staging in women with endometrial cancer over a 12 year period. The authors noted that the use of whole pelvic radiation decreased from 16% to 9%. In an evaluation of women with all stages of endometrial cancer, it was noted that unstaged patients were twice as likely to receive some form of adjuvant radiation as those who underwent lymph node evaluation.
Our findings suggest that patients with stage I-II endometrial cancer who undergo lymphadenectomy are less likely to receive external pelvic radiotherapy and more likely to undergo treatment with vaginal brachytherapy. These findings are most pronounced for patients with intermediate risk (stage IB grades 2 and 3 and IC grades 1 and 2) tumors.
Among women without nodal metastases, the primary rationale for radiation is to prevent locoregional recurrence.
Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
A recent randomized trial of women with apparent stage I-IIA endometrial cancer (Post-Operative Radiation Therapy for Endometrial Carcinoma [PORTEC]-2) demonstrated that vaginal brachytherapy was not inferior to whole pelvic radiation.
Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
These data suggest that whole pelvic radiation can safely be omitted in favor of brachytherapy in those patients with corpus-confined disease in whom radiation is elected.
Patients with unstaged endometrial cancer present a difficult dilemma in that vaginal brachytherapy is inadequate treatment for women with unrecognized nodal disease. Although lymphadenectomy was not required for entry into the PORTEC-2 trial, it is unclear whether clinicians in the United States would consider vaginal brachytherapy adequate treatment for women with unstaged high-intermediate risk disease. A survey of US gynecologic oncologists reported that these physicians were 23% less likely to administer radiation to women with grade 1 tumors with 50-66% myoinvasion in women who underwent lymphadenectomy compared with patients who had not undergone nodal evaluation.
PORTEC Study Group Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial Post Operative Radiation Therapy in Endometrial Carcinoma.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.
Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
In the GOG's evaluation of pelvic radiation for intermediate-risk endometrial cancer, treatment was associated with an increased risk of hematologic, gastrointestinal, genitourinary, and cutaneous complications.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.
The side effect profile of radiation is improved when vaginal brachytherapy is substituted for external beam treatment. The PORTEC-2 investigators noted that the rate of gastrointestinal toxicity was 4-fold lower in patients treated with brachytherapy compared with those who received external beam radiation.
Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
In addition to direct costs, pelvic radiotherapy is typically administered over a course of 5-6 weeks and requires a significant time commitment from patients. In our analysis, performance of lymphadenectomy in only 5 patients younger than 60 years of age or 7 patients older than 60 years of age with stage IC grade 2 tumors would be required to avoid 1 course of pelvic radiation.
The most important question addressed by our study is which patients derive the most benefit from lymphadenectomy. Our findings suggest that patients with stage IB and IC tumors are most likely to have their adjuvant treatment influenced by lymphadenectomy. Although prior work has demonstrated the difficulty in predicting final tumor grade and depth of invasion based on preoperative biopsy and intraoperative inspection, we noted that even women with low-grade, superficially invasive tumors were less likely to receive pelvic radiation if they underwent lymphadenectomy.
We also noted that the extent of lymphadenectomy performed appeared to influence treatment allocation. The reduced use of external beam radiation among patients with intermediate risk tumors was most pronounced in patients who had 10 or more nodes removed. Although prior studies of endometrial cancer have suggested that the extent of lymphadenectomy influences survival, our data suggest that node count also has a direct impact on the allocation of adjuvant treatment.
Although our analysis benefits from the inclusion of a large number of patients, we recognize several important limitations. Because SEER lacks data on chemotherapy, our study was limited to examining the influence of lymphadenctomy on the prescription of radiotherapy. Although uncommon during the years of study, adjuvant chemotherapy for women with early-stage endometrial cancer is now more frequently utilized.
Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study.
Although SEER captures data on the type of radiation administered, the database lacks details on total dose of radiation, treatment fields, and duration of treatment.
Given these limitations, we restricted our analysis to simply determining whether external beam radiation or brachytherapy was administered. Our study utilized the 1988 FIGO staging criteria. FIGO has recently implemented a revised staging schema, and our findings may have differed somewhat using the updated system. Finally, although we stratified our analysis by 3 of the factors most important in the use of adjuvant treatment (age, stage, and grade), a number of individual patient and physician factors have an impact on the allocation of treatment and may have influenced our results.
Our findings suggest that lymphadenectomy plays an important role in the allocation of adjuvant treatment for women with stage I and II endometrial cancer. Those women who undergo lymphadenectomy are less likely to receive whole pelvic radiotherapy. The effects of lymphadenectomy are most pronounced in women with high-intermediate risk tumors and greatest for patients who have 10 or more nodes removed. In aggregate are data support lymphadenectomy for the majority of women with endometrial cancer. Those women who undergo lymphadenectomy should have at least 10 nodes removed as specified by the GOG.
Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study.
Surveillance, Epidemiology, and End Results, SEER*Stat Database: incidence-SEER 9 regs limited-use, Nov 2006 Sub (1973-2004), National Cancer Institute, Division of Cancer Control and Population Sciences, Surveillance Research Program, Cancer Statistics Branch, released April 2007, based on the November 2006 submission.
Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study.
Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study.
Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial.
Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study.
This study was supported by the Milstein Family Research Fund.
The authors report no conflict of interest.
Cite this article as: Sharma C, Deutsch I, Lewin SN, et al. Lymphadenectomy influences the utilization of adjuvant radiation treatment for endometrial cancer. Am J Obstet Gynecol 2011;205:562.e1-9.
We read, with great interest, the article by Sharma et al,1 in which, in a large retrospective study on data from the National Cancer Institute's Surveillance, Epidemiology, and End Results database, the authors analyzed women with stages I-II endometrioid adenocarcinomas of the uterine corpus treated between 1988 and 2006. Findings suggest that, especially among women with high- to intermediate-risk tumors, patients who undergo lymphadenectomy are less likely to receive external-beam radiation.
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