jgo Journal of Gynecologic Oncology J Gynecol Oncol 2005-0380 2005-0399 Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, Japan Society of Gynecologic Oncology 10.3802/jgo.2017.28.e76 jgo-28-e76 Original Article Assessing the effect of guideline introduction on clinical practice and outcome in patients with endometrial cancer in Japan: a project of the Japan Society of Gynecologic Oncology (JSGO) guideline evaluation committee ShigetaShogo 1 NagaseSatoru 2 MikamiMikio 3 IkedaMasae 3 ShidaMasako 3 SakaguchiIsao 4 UshiodaNorichika 5 TakahashiFumiaki 6 YamagamiWataru 7 YaegashiNobuo 1 UdagawaYasuhiro 8 KatabuchiHidetaka 4 Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan Department of Obstetrics and Gynecology, Yamagata University Faculty of Medicine, Yamagata, Japan Department of Obstetrics and Gynecology, Tokai University School of Medicine, Isehara, Japan Department of Obstetrics and Gynecology, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan Department of Obstetrics and Gynecology, Kawasaki Medical School, Kurashiki, Japan Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan Department of Obstetrics and Gynecology, Dokkyo Medical University, Tochigi, Japan Correspondence to Shogo Shigeta Department of Obstetrics and Gynecology, Tohoku University School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. E-mail: s.shigeta@med.tohoku.ac.jp 11 2017 04 11 2017 28 6 e76 01062017 07072017 23072017 Copyright © 2017 Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Objective

The Japan Society of Gynecologic Oncology (JSGO) published the first practice guideline for endometrial cancer in 2006. The JSGO guideline evaluation committee assessed the effect of this guideline introduction on clinical practice and patient outcome using data provided by the Japan Society of Obstetrics and Gynecology (JSOG) cancer registration system.

 Methods

Data of patients with endometrial cancer registered between 2000 and 2012 were analyzed, and epidemiological and clinical trends were assessed. The influence of guideline introduction on survival was determined by analyzing data of patients registered between 2004 and 2009 using competing risk model.

 Results

In total, 65,241 cases of endometrial cancer were registered. Total number of patients registered each year increased about 3 times in the analyzed period, and the proportion of older patients with type II endometrial cancer rapidly increased. The frequency of lymphadenectomy had decreased not only among the low-recurrence risk group but also among the intermediate- or high-recurrence risk group. Adjuvant therapy was integrated into chemotherapy (p<0.001). Overall survival did not significantly differ before and after the guideline introduction (hazard ratio [HR]=0.891; p=0.160). Additional analyses revealed patients receiving adjuvant chemotherapy showed better prognosis than those receiving adjuvant radiation therapy when limited to stage I or II (HR=0.598; p=0.003).

 Conclusion

It was suggested that guideline introduction influenced the management of endometrial cancer at several aspects. Better organized information and continuous evaluation are necessary to understand the causal relationship between the guideline and patient outcome.

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Trends of patient characteristics. (A) Number of patients and facilities per year. (B) Age distribution per year. Patients aged >60 years significantly increased (p<0.001). (C) Histological subtype distribution per year. Trend test revealed significant increases in the frequency of serous adenocarcinoma, and in the population of both serous and clear cell carcinoma (p<0.001).

Trends of clinical practice in endometrial cancer management. (A) Distribution of initial treatment by year. Among surgeries, the proportion of LA procedures had significantly decreased (Cochran-Armitage trend test, p<0.001). (B) Trend of adjuvant therapy in each year. The proportion of adjuvant chemotherapy had significantly increased among the adjuvant therapies (Cochran-Armitage trend test, p<0.001). EBRT, extra-beam radiation therapy; ICBT, intracavitary brachytherapy; LA, lymphadenectomy.

Patient characteristics

Parameters No. of patients (%)
Age (yr)
    ≤29 514 (0.8)
    30–39 3,474 (5.3)
    40–49 9,043 (13.9)
    50–59 22,791 (34.9)
    60–69 17,371 (26.6)
    70–79 9,451 (14.5)
    ≥80 2,597 (4.0)
FIGO stage*
    I 42,562 (65.2)
    II 5,458 (8.4)
    III 12,700 (19.5)
    IV 4,517 (6.9)
    Unknown 4 (0.0)
Histology
    Endometrioid
        Grade 1 32,245 (49.4)
        Grade 2 14,497 (22.2)
        Grade 3 6,980 (10.7)
        Unknown 1,418 (2.2)
    Serous 2,582 (4.0)
    Clear cell 1,493 (2.3)
    Mucinous 367 (0.6)
    Others/unknown 5,659 (8.7)
Primary treatment
    Surgery
        With LA 44,525 (68.2)
        Without LA 16,740 (25.7)
    Chemotherapy 2,237 (3.4)
    EBRT 684 (1.0)
    ICBT 101 (0.2)
    Hormonal therapy 742 (1.1)
    Others/unknown 212 (0.3)

EBRT, extra-beam radiation therapy; FIGO, International Federation of Gynecology and Obstetrics; ICBT, intracavitary brachytherapy; LA, lymphadenectomy.* For postoperative staging, 1988 FIGO staging criteria were adopted from 2000 to 2011. FIGO clinical staging criteria were also employed from 2000 to 2011. 2009 FIGO staging criteria were adopted for the all cases registered in 2012.

Frequency of LA between pre- and post-guideline publication

Stages No. of patients (%)
2000–2006 2007–2012 (All)
With LA Without LA With LA Without LA
All* 18,777 (75.5) 6,101 (24.5) 25,747 (70.8) 10,636 (29.2)
Ia† 2,801 (61.1) 1,788 (38.9) 3,049 (55.9) 2,406 (44.1)
Ib† 6,731 (78.1) 1,886 (21.9) 7,167 (75.1) 2,373 (24.9)
Ic 2,609 (78.8) 701 (21.2) 2,952 (77.0) 883 (23.0)
IIa† 663 (79.4) 172 (20.6) 760 (73.1) 279 (26.9)
IIb 1,032 (81.9) 228 (18.1) 1,193 (79.6) 305 (20.4)
IIIa 2,180 (79.4) 564 (20.6) 2,494 (78.1) 698 (21.9)
IIIb 73 (66.4) 37 (33.6) 67 (60.9) 43 (39.1)
IIIc† 2,132 (93.8) 142 (6.2) 2,280 (92.0) 197 (8.0)
IVa 45 (48.9) 47 (51.1) 41 (45.1) 50 (54.9)
IVb 460 (50.4) 453 (49.6) 584 (46.3) 676 (53.7)

LA, lymphadenectomy.

It shows significant difference between 2000–2006 and 2007–2012 using χ2 test (p<0.001);

It shows significant difference between 2000–2006 and 2007–2011 using χ2 test (p<0.050).

Multivariate analysis of the influence of the guideline publication

Parameters HR 95% CI p-value
2004–2006 1.000 (reference) – –
2007–2009 0.891 0.759–1.046 0.160
Year 1.020 0.972–1.069 0.423
Age 1.002 1.001–1.002 <0.001
Stage
    I 1.000 (reference) – –
    II 2.281 1.913–2.718 <0.001
    III 5.695 5.079–6.387 <0.001
    IV 14.017 12.287–15.990 <0.001
Histology
    Endometrioid grade 1 1.000 (reference) – –
    Endometrioid grade 2 2.481 2.166–2.842 <0.001
    Endometrioid grade 3 4.149 3.594–4.790 <0.001
    Endometrioid grade unknown 3.372 2.595–4.381 <0.001
    Serous/clear-cell 5.424 4.690–6.272 <0.001
    Others 6.712 5.833–7.723 <0.001
Primary treatment
    Surgery with LA 1.000 (reference) – –
    Surgery without LA 1.992 1.810–2.192 <0.001
    Radiation therapy* 4.969 3.842–6.427 <0.001
    Chemotherapy 2.508 2.198–2.862 <0.001
    Others 4.828 3.228–7.221 <0.001

CI, confidence interval; EBRT, extra-beam radiation therapy; HR, hazard ratio; ICBT, intracavitary brachytherapy; LA, lymphadenectomy.* Including both EBRT and ICBT.

Multivariate analysis of adjuvant therapy

Parameters HR 95% CI p-value
Surgery 1.000 (reference) – –
Surgery+adjuvant chemotherapy 1.102 0.916–1.325 0.302
Surgery+radiation therapy* 1.841 1.316–2.577 <0.001
Surgery+others 1.340 0.591–3.037 0.483

CI, confidence interval; EBRT, extra-beam radiation therapy; HR, hazard ratio; ICBT, intracavitary brachytherapy.* Including both EBRT and ICBT.