Adjunct Metformin helps reversal of atypical endometrial hyperplasia

Adjunct metformin treatment help reversal of atypical endometrial hyperplasia (AEH) and improves overall survival in endometrial cancer reports the result of a systematic review and meta-analysis published ahead of print in Journal of Gynecologic Oncology.

Metformin is named as ‘Magic Bullet’ by some researchers because of its new-found role in reversing aging to improving survival in many cancers, besides being in use as antidiabetic and cardioprotective drug since nearly 60 years.

Metformin was introduced for use as antidiabetic in UK in 1958.

Endometrial cancer (EC) is one of the most common gynecological cancer. The American Cancer Society estimates that about 61,380 new cases of EC of the uterus (uterine body or corpus) will be diagnosed in 2017 and about 10,920 women will succumb to the disease.

This systematic review and meta-analysis searched Cochrane, LILACS, PubMed, Scopus and Web of Science in January 2017 and included 19 eligible studies that included information about reversal of atypical endometrial hyperplasia, cellular proliferation biomarkers expression and overall survival in metformin-users compared to non-users.

In 5 studies, metformin led to reversion of AEH to a normal histology and decreased cell proliferation biomarkers staining, from 51.94% to 34.47%.

Patients on adjunct metformin had 18% increased odds of survival as compared to patients who were not diabetic and not on metformin. (HR = 0.82; CI: 0.70–0.95; p = 0.09, I2 = 40%).

Type 2 diabetes mellitus and insulin resistance is involved in the etiology of endometrial cancer (EC), so metformin may have both direct and indirect effect on tumor regression.

There was considerable heterogenicity observed between the studies but, despite that metformin was shown to be beneficial in reversal of AEH and improving overall survival in EC.

The authors call  upon future need of prospective trials regarding the anticancer effect of metformin and improving the clinical outcomes in EC.  

Primary source: Effects of metformin on endometrial cancer: Systematic review and meta-analysis

Meireles, Cinthia G. et al.

Gynecologic Oncology , Volume 0 , Issue 0 ,

Endometrial cancer management guidelines updated: assorting the uncertainties! -----2

The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy.

These guidelines were published in an article by Colombo N et al in January issue of Annals of Oncology. 

These guidelines were developed based on 12 questions identified by the expert panel. 

The first question was addressed in part 1: Which surveillance should be used for asymptomatic women?

The second question is: What work-up and management scheme should be undertaken for fertility-preserving therapy in patients with atypical hyperplasia (AH)/endometrial intraepithelial neoplasia (EIN) and grade 1 endometrioid endometrial cancer (EEC)?

 

It’s rare that young women of childbearing age will be diagnosed with EC, with only 4% of all patients being younger than 40 years of age. 

Younger women also have a better prognosis, being at early and low grade stage of disease when diagnosed. The standard approach in women of childbearing age is hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy. This procedure has a very good survival ( 93% at 5 years) but results in permanent loss of reproductive capacity. 

The conservative management consist of medical therapy with progestins (oral or local) for premalignant and grade 1 EC.

Recommendation 2.1: Patients with AH/EIN or grade 1 EEC requesting fertility-preserving therapy must be referred to specialised centres. Level of evidence: V, Strength of recommendation: A

Recommendation 2.2: In these patients, D&C with or without hysteroscopy must be performed .Level of evidence: IV, Strength of recommendation: A 

Recommendation 2.3: AH/EIN or grade 1 EEC must be confirmed/diagnosed by a specialist gynaecopathologist .Level of evidence: IV,Strength of recommendation: A

Recommendation 2.4: Pelvic MRI should be performed to exclude overt myometrial invasion and adnexal involvement. Expert ultrasound can be considered as an alternative.Level of evidence: III, Strength of recommendation: B

Recommendation 2.5: Patients must be informed that fertility-sparing treatment is a non-standard treatment and the pros and cons must be discussed. Patients should be willing to accept close follow-up and be informed of the need for future hysterectomy.Level of evidence: V,Strength of recommendation: A

Recommendation 2.6: For patients undergoing fertility-preserving therapy, MPA (400–600 mg/day) or MA (160–320 mg/day) is the recommended treatment. However, treatment with LNG-IUD with or without GnRH analogues can also be considered.Level of evidence: IV,Strength of recommendation: B

Recommendation 2.7: In order to assess response, D&C, hysteroscopy and imaging at 6 months must be performed. If no response is achieved after 6 months, standard surgical treatment should be performed. Level of evidence: IV,Strength of recommendation: B

Recommendation 2.8: In case of complete response, conception must be encouraged and referral to a fertility clinic is recommended.Level of evidence: IV, Strength of recommendation: B

Recommendation 2.9: Maintenance treatment should be considered in responders who wish to delay pregnancy.Level of evidence: IV,Strength of recommendation: B

Recommendation 2.10: Patients not undergoing hysterectomy should be re-evaluated clinically every 6 months.Level of evidence: IV,Strength of recommendation: B

Recommendation 2.11: After completion of childbearing, a hysterectomy and salpingo-oophorectomy should be recommended. The preservation of the ovaries can be considered depending on age and genetic risk factors. Level of evidence: IV, Strength of recommendation: B 

Pregnancy is protective for endometrial cancer and the pooled pregnancy rate in a recent metaanalysis was 28%, which reached 39% when assisted reproductive technology was used.
  

To be continued…..

References:

Colombo N,Creutzberg CL, Amant F et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: diagnosis, treatment and follow-up. Ann Oncol 2016; 27: 16–41.