Fertility preserving treatments for endometrial cancer: The unanswered questions

Abstract

Women with grade 1 endometrial cancer without myometrial invasion (consistent with FIGO 1988 stage Ia) treated by conventional surgery have a disease-specific survival of 99.2% after 5 years, and 98% after 10 years [ [1] Lajer H. Elnegaard S. Christensen R.D. Ortoft G. Schledermann D.E. Mogensen O. Survival after stage lA endometrial cancer; can follow-up be altered? A prospective nationwide Danish survey. Acta Obstet Gynecol Scand. 2012; 91: 977-982 Crossref Scopus (41) Google Scholar ]. Due to the excellent cure rates obtained for these specific cancers, it has been possible to shift the focus from efforts to prolong survival towards quality of life issues after treatment. In particular, there has been increased attention focused on fertility preservation, as around 10% of patients with endometrial cancer are afflicted by the disease during the reproductive phase of their life. Considering the average age at first birth has steadily increased in developed nations, now reaching 1 in 12 births in women above the age of 35 (compared to only 1 in 100 in 1970) [ [2] Mathews TJ, Hamilton BE. Delayed childbearing: more women are having their first child later in life. NCHS data brief, no 21. Hyattsville, MD: National Center for Health Statistics. Google Scholar ], it is not surprising that many of these younger women with endometrial cancer desire treatment which preserves the ability to have children. In addition, the underlying hyperestrogenic state that contributes to the development of endometrial cancer in these women, may also be associated with infertility prior to the diagnosis of cancer. Thus for many women decisions concerning the therapeutic approach for endometrial cancer will be influenced by the desire to maintain or improve fertility. Although the first publication describing fertility preserving, conservative treatment with hormones was published in 1961 [ [3] Kelley R.M. Baker W.H. Progestational agents in the treatment of carcinoma of the endometrium. NEJM. 1961; 264: 216 Crossref PubMed Scopus (165) Google Scholar ], the number of publications describing the outcome is still limited (around 40 manuscripts, 620 patients [ 4 Gallos I.D. Yap J. Rajkhowa M. et al. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012; 207: e1-e12 PubMed Google Scholar , 5 Park J.Y. Kim D.Y. Kim J.H. Kim Y.M. KIM K.R. Kim Y.T. et al. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013; 49: 868-874 Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar ]) and many questions remain unanswered. Summarizing as much as possible the information published up to the end of 2012 reveals that conservative treatment resulted in resolution of endometrial cancer in approximately 76% of 408 reported patients, with less than 1% of reported cases showing a poor outcome. However, only 22% of 325 patients achieved live births, and 41% of 267 evaluable patients eventually recurred [ 4 Gallos I.D. Yap J. Rajkhowa M. et al. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012; 207: e1-e12 PubMed Google Scholar , 5 Park J.Y. Kim D.Y. Kim J.H. Kim Y.M. KIM K.R. Kim Y.T. et al. Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer. 2013; 49: 868-874 Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar ]. In view of the relatively high recurrence rate, young women with relapse after hormonal treatment may still desire fertility, requiring consideration of repeat fertility-sparing treatment to allow additional pregnancies [ [6] Gotlieb W.H. Beiner M.E. Shalmon B. Korach Y. Segal Y. Zmira N. et al. Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer. Obstet Gynecol. 2003; 102: 718-725 Crossref PubMed Scopus (198) Google Scholar ].