Is repeated high-dose medroxyprogesterone acetate (MPA) therapy permissible for patients with early stage endometrial cancer or atypical endometrial hyperplasia who desire preserving fertility?

Abstract

ObjectiveReports on the repeated administration of medroxyprogesterone acetate (MPA) for intrauterine recurrence after fertility-preserving therapy for atypical endometrial hyperplasia (AEH) and early grade 1 endometrioid carcinoma (G1) are lacking. We aimed to clarify the outcomes of repeated MPA therapy in cases of intrauterine recurrence after fertility-preserving therapy with MPA against AEH/early G1.MethodsPatients with AEH or stage IA well-differentiated endometrioid carcinoma without myometrial invasion who underwent first-line MPA therapy for primary lesions or intrauterine recurrence were divided into initial treatment and repeated treatment groups (162 and 82 patients, respectively). Oral MPA administration (400−600 mg/day) was continued until pathological tumor disappearance. Data regarding clinicopathological factors, adverse events, and outcomes following the initial and repeated hormonal treatments were extracted from medical records and analyzed.ResultsComplete response rates in the initial and repeated treatment groups were 98.5% and 96.4%, respectively, among patients with AEH, and were 90.7% and 98.1%, respectively, among patients with G1. In the initial treatment group, 5-year recurrence-free survival (RFS) rates were 53.7% and 33.2% among patients with AEH and G1, respectively. In the repeated treatment group, RFS rates were 14.0% and 11.2% among patients with AEH and G1, respectively. Among patients with AEH, the pregnancy rate tended to be lower in the repeated treatment group than in the initial treatment group (11.1% vs. 29.2%; p=0.107), while no significant group difference was observed among patients with G1 (20.8% vs. 22.7%).ConclusionRepeated treatment is sufficiently effective for intrauterine recurrence after hormonal therapy for AEH/early G1.

Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer

“…Currently, conservative treatment with hormones such as medroxyprogesterone acetate is used for early-stage early-onset endometrial cancer without myometrial invasion or extrauterine spread (5). However, we have reported previously that the recurrence rate after medroxyprogesterone acetate therapy is 63.2% and the resulting pregnancy rate lower than would be desired (6). In order to improve the outcome of medical treatment for patients with endometrial cancer, there is a need to clarify the molecular basis of endometrial carcinogenesis, especially in young patients.…”

Unique Molecular Features in High-Risk Histology Endometrial Cancers

“…A study conducted in Japan found a complete response rate of 90.7% in women with early-stage low-grade endometrioid carcinoma, and 20% of women went on to have a successful pregnancy. However, 5-year recurrence-free survival was only 33% [75]. Thus, it is critical that women understand that fertility-sparing treatment is not a cure.…”

Hysteroscopic Photodynamic Diagnosis Using 5-Aminolevulinic Acid: A High-Sensitivity Diagnostic Method for Uterine Endometrial Malignant Diseases

“…The high sensitivity of hysteroscopic 5ALA-PDD may improve the prognosis of fertility preservation therapy. Currently, MPA therapy is performed as a treatment option in patients with early EC and AEH who desire fertility preservation [4]; however, the recurrence rate is high [5,6], and the pregnancy rate is decreased because of endometrial damage by repeated D&C and hysteroscopic resection [9,10]. It is possible that hysteroscopic 5ALA-PDD may increase the complete resection rate like cystoscopic 5ALA-PDD [17].…”

“…Progestins such as medroxyprogesterone acetate (MPA) and megestrol acetate are used for fertility preservation therapy [4], but this treatment has a high recurrence rate. Yamagami et al [5] found 5-year recurrence-free survival rates after MPA therapy of 53.7% and 33.2% in patients with AEH and EC grade 1, respectively, and Hahn et al [6] reported a 40% recurrence rate after hormonal treatment for early-stage EC. Hysteroscopic tumor resection in addition to hormone therapy may improve the prognosis of fertility preservation therapy [7,8], but repeated dilation and curettage (D&C) and hysteroscopic resection results in a reduced pregnancy rate [9] owing to endometrial damage [10].…”