Elsevier

Gynecologic Oncology

Volume 124, Issue 3, March 2012, Pages 542-548
Gynecologic Oncology

Predictors of resolution of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma in premenopausal women treated with progestin therapy

https://doi.org/10.1016/j.ygyno.2011.11.004Get rights and content

Abstract

Objective

To identify clinical and pathologic predictors of response to progestin treatment in premenopausal women with complex atypical hyperplasia (CAH) and Grade 1 endometrial adenocarcinoma (Grade 1 EA).

Methods

Forty premenopausal patients with Grade 1 EA or CAH who underwent progestin therapy for a minimum of 8 weeks were retrospectively identified. Patient characteristics and histopathologic features of pretreatment and first follow-up endometrial specimens were evaluated as predictors of resolution, defined as absence of hyperplasia or carcinoma.

Results

Kaplan–Meier analysis indicated 63% resolution at 18 months of follow-up. Multivariate classification analysis showed that resolution rates were higher in individuals with a low pre-treatment qualitative abnormal architecture score and a BMI < 35 (Standardized Resolution Ratio (SRR) = 1.48, p = 0.03). The diagnosis of benign endometrium or simple hyperplasia on the first follow-up specimen was highly predictive of resolution (SRR = 2.25, p = 0.002). Resolution rates were lower among subjects with a high pre-treatment qualitative abnormal architecture score (SRR = 0.37, p < 0.03) and lowest in subjects whose first follow-up specimen showed persistent complexity, atypia, or carcinoma with adjacent stromal decidualization (SRR = 0.24, p = 0.002).

Conclusions

Clinical and pathologic parameters can predict response to progestin therapy in premenopausal women with CAH and Grade 1 EA. A low likelihood of resolution is predicted by an unfavorable pre-treatment architectural score and lack of pathological response in the first specimen, despite adjacent stromal decidualization.

Highlights

► Progestin for grade 1 endometrial cancer and CAH—clinical & pathological predictors of resolution. ► 43% resolution at 12 months; 63% resolution at 18 months. ► Lowest resolution rate if no response on 1st follow-up specimen & adjacent stromal decidualization.

Section snippets

Introduction and background

Endometrial cancer is the most common gynecologic malignancy in developed countries [1]. While typically a disease of postmenopausal women, 20–25% of endometrial cancer and complex atypical hyperplasia cases occur in premenopausal women, with 5–10% occurring in women under the age of 40 [2], [3]. For the subpopulation of fertility-seeking premenopausal women with complex atypical hyperplasia (CAH) or grade 1 endometrial adenocarcinoma (Grade 1 EA), progestin therapy may enable a delay of

Methods

Premenopausal women diagnosed with Grade 1 EA or CAH between 1998 and 2007 were identified from pathology and gynecologic oncology databases at Olive View-UCLA, Cedars-Sinai, and UCLA Medical Centers. Institutional review board approval was obtained from all three institutions. A retrospective chart review was performed to extract clinical, epidemiological, pathological, and treatment data. Inclusion criteria were a diagnosis of CAH or Grade 1 EA on pre-treatment sampling, followed by progestin

Results

Forty premenopausal patients with Grade 1 EA or CAH met study criteria. Demographic and clinical data are described in Table 1. Median time from diagnosis to first follow-up was 3.8 months (range 2.3–8.2 months). The initial diagnosis was Grade 1 EA in 35% of subjects and CAH in 65%. Concordance in the histopathological diagnosis of the pretreatment specimen was found in 90% of specimens (κ = 0.82, p < 0.00001); in the remaining 10%, additional review by a third pathologist confirmed the original

Discussion

Progestin therapy offers a potential medical treatment for premenopausal women with complex atypical hyperplasia (CAH) or grade 1 endometrial cancer (Grade 1 EA) who desire to maintain fertility. Combining cases of CAH and Grade 1 EA from the literature plus the data from this study shows 353 patients with 67% resolution (Table 3). This retrospective study is the first to further identify clinical and pathologic predictors of success of progestin treatment in premenopausal women. In our study

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgment

We thank Jeffrey Gornbein, PhD, Department of Biostatistics, David Geffen School of Medicine at University of California, Los Angeles, for assistance with the statistical analysis.

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