Malignant Transformation of Postmenopausal Endometriosis: A Systematic Review of the Literature

SIMPLE SUMMARY: Endometriosis is a disease that affects 6–10% of women of reproductive age. Although it is a benign condition, endometriotic lesions have around a 1% risk of malignant transformation. Since endometriosis is an estrogen-dependent disease, it can be expected to resolve or disappear in menopause. However, the prevalence of menopausal endometriosis is 2–4%. In these cases, the risk of malignant transformation is a rare but possible event. Data on the risk of these occurrences are scarce and of low quality. The most studied risk factors related to malignant transformation were hormone replacement therapy and the use of tamoxifen. However, the results were inconclusive. Furthermore, the impact of previous endometriosis and related surgery is unclear. Thus, we felt the need for an updated review on this topic focusing on the distribution of recurrent clinical conditions over a period of 50 years. In this regard, a systematic literature review on the malignant transformation of endometriosis-related lesions in postmenopause was performed to provide useful clinical information about patient characteristics, HRT use, and outcomes. ABSTRACT: Objective: This study aimed to systematically review the existing literature on malignant transformation of postmenopausal endometriosis to provide information about patient characteristics, hormonal replacement therapy (HRT) use, and outcomes over a period of 52 years (1969–2021). Methods: According to PRISMA guidelines, we searched for (endometriosis OR endometriotic) AND (cancer OR malignancy OR malignant transformation) AND (menopause OR menopausal OR postmenopause OR postmenopausal) in Pubmed (all fields) (accessed on 12 February 2021) and Scopus (Title/Abstract/Keywords) (accessed on 12 February 2021) databases. The only filter used was the English language. Relevant articles were obtained in full-text format and screened for additional references. Eligibility/inclusion criteria: studies including full case description of malignant transformation of endometriosis-related lesions in postmenopause. Results: 75 studies, including 90 cases, were retrieved. The mean age was 55.8 ± 8.5 years. Overall, about 65% of women had a positive personal history of endometriosis/adenomyosis, and 64% of women underwent previous hysterectomy ± bilateral salpingo-oophorectomy. Forty-nine of 74 women used HRT (66.2%). Among the women who used HRT, estrogen-only treatment was taken by approximately 75%. Duration of HRT was longer than five years in 63.3% of cases. About 70% of subjects had histology of endometrioid adenocarcinoma or clear cell carcinoma. Follow-up outcome, available for 61 women, showed a survival rate of 78.7%, recurrence of 9.8%, death of 11.5%. The duration of follow-up had a median of 12 months (interquartile range, 6.75–25 months). Interestingly, over the years of case publication there was a significant inverse correlation with previous history of endometriosis (r = −0.28, p = 0.007), HRT use (r = −0.31, p = 0.006), and previous definitive surgery (r = −0.42, p < 0.001). Conclusions: In the malignant transformation of postmenopausal endometriosis, there are some recurrent clinical conditions: previous endometriosis, major definitive surgery before menopause, and estrogen-only HRT for a relatively long time. However, these clinical conditions have shown a drastic decrease over time. This could likely be the consequence of different attitudes and management of gynecologists linked to up-to-date scientific evidence about the use of major surgery in gynecological pathologies. Malignant transformation of postmenopausal endometriosis is a clinical challenge to be explored further.