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Significance of serum and pathological biomarkers in fertility-sparing treatment for endometrial cancer or atypical hyperplasia: a retrospective cohort study.

ABSTRACT:

Background

This study analyzed the changes of serum and pathological biomarkers during fertility-sparing therapy of endometrial cancer (EC) or endometrial atypical hyperplasia (EAH), to investigate their implications for early prediction of treatment efficacy.

Methods

A retrospective analysis of EC or EAH patients who received fertility-sparing therapy between 2012 and 2016 was performed. Serum and endometrium sampling were obtained for each patient at three time points: at baseline, at 3-6 months' treatment and at the end of conservative treatment. Serum biomarkers including insulin resistance (HbA1c, HOMA-IR), sex hormones and thyroid hormones were measured. Meanwhile expression of endometrial pathological biomarkers including ER, PR, PRB and Ki-67 was also assessed by immunohistochemistry.

Results

For the 53 recruited patients, overall complete response, recurrence and pregnancy rates were 94%, 26% and 36.4%. During the treatment, the serum biomarkers of HOMA-IR remained stable, while pathological markers including PR, PRB and Ki67 diminished significantly. Patients who achieved remission faster had significant lower HOMA-IR level and higher PRB expression at baseline. We also found a more remarkable down-regulation of PRB related with faster remission. Further multivariate analysis confirmed that baseline HOMA-IR ≥ 2.5 negatively affected treatment time to remission (OR 0.206; p = 0.017). While marked reduction of PRB (≥ 30%) at 3-6 months' treatment correlated with faster remission (OR 5.788; p = 0.010).

Conclusion

For EC and EAH patients who received fertility-sparing therapy, baseline status of insulin resistance predicted poor response to progestin, while marked reduction of PRB following the initial 3-6 months' treatment predicted fast remission.

SUBMITTER: Wang Y

PROVIDER: S-EPMC8223344 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAround 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes.MethodsThis study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence.Ethics and disseminationThe protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal.ConclusionsProspective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH.Trial registration numberChinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.