Objective
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.
For Editors’ Commentary, see Table of Contents
See related editorial, page 509
Metastasis to the pelvic and paraaortic lymph nodes is widely recognized as the most important prognostic factor for endometrial cancer. 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. 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. Proponents of the procedure argue that it provides important prognostic information and helps to guide adjuvant treatment planning. 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.
Given the conflicting data on lymphadenectomy, performance of the procedure is now actively debated. 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. SEER comprises several geographically distinct tumor registries. Data from SEER 17 registries was utilized. 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 χ 2 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).
| 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) |
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).
| 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 |
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