Health Concerns

Endometrial Cancer

Conventional Treatment

Surgery is the mainstay of treatment in most cases of isolated endometrial cancer. Radiation therapy, hormone therapy, and chemotherapy may be used to complement surgery in these cases, but play more of a role in the treatment of recurrent or disseminated cancer for which surgery is unlikely to be curative (Wright 2012; Arora 2012; Baker 2007).

Surgery

Patients with stage I endometrial cancer typically undergo hysterectomy (ie, removal of the uterus). In order to allow for maximal removal of cancerous lesion(s), the fallopian tubes and ovaries are also removed in a procedure called a bilateral salpingo-oophorectomy (BSO) (Lewandowski 1990; Juretzka 2005). Removal of the uterus through the abdomen (abdominal hysterectomy) may offer some advantages over vaginal hysterectomy, since the former procedure allows the surgeon to directly examine the abdominal wall and cavity and to remove tissues for biopsy (Wright 2012; Amant 2005; Arora 2012; Kristensen 2004). Laparoscopic hysterectomy is a less invasive option which has gained popularity. This technique involves small incisions in the abdomen and specialized instruments for visualization and removal of tissue (Fram 2013; Kaiser Permanente [undated]).

Radiation Therapy

While surgery alone is a good treatment option in women with low-risk endometrial cancer, patients with later stages of the disease typically undergo BSO in combination with radiation therapy (RT), especially if they have high-risk disease (Creutzberg 2011). Radiation is typically delivered either through the use of an external beam (EBRT) or via a device implanted internally (ie, vaginal brachytherapy) (Nag 2000; Nout 2010; Creutzberg 2011).

Chemotherapy

Chemotherapy may be prescribed to patients after the uterus and locally affected tissues are surgically removed.  Women with advanced and/or recurrent endometrial cancer are typically prescribed chemotherapeutic drugs which may include carboplatin (Paraplatin®), paclitaxel (Taxol®), doxorubicin (Adriamycin®), and others (Akram 2005; Duska 2005; Randall 2006; Shimada 2007).

Although as many as 40-60% of endometrial cancer patients initially respond to chemotherapy, recurrences may appear after only a few months. Approximately 10-15% of patients with early stage endometrial cancer experience recurrences. Some studies reported recurrence rates of about 50% in advanced disease (Emons 2000; Amant 2005; Odagiri 2011).

Hormone Therapy

Since estrogens can promote the development and progression of endometrial cancer, treatment with synthetic progesterone-like drugs called progestins was one of the first pharmacologic interventions developed (Lewis 1974; Apgar 2000).

Synthetic progestins are typically administered orally in pill form, but can also be intramuscularly injected, as in the case of medroxyprogesterone acetate (MPA, or Depo-Provera®) (Hesselius 1981; Kaunitz 1994; Apgar 2000; Ushijima 2007; Park 2013). Synthetic progestin therapy has only been shown to be effective in endometrial cancer patients whose tumor(s) express progesterone’s target molecule, the progesterone receptor (Dai 2002; Dai 2005; Punnonen 1993; Creasman 1993; Fukuda 1998; Banno 2012).

This form of cancer treatment is typically administered to patients who cannot undergo surgery, require palliative treatment, or when cancer occurs in women of childbearing age who want to have children after diagnosis (Apgar 2000; Emons 2000; Banno 2012). Patients on synthetic progestin therapy need to be monitored closely as the disease can progress during or after this treatment (ACS 2013b).

Natural progesterone also exerts several anti-cancer effects in endometrial tissue, primarily related to cell differentiation. In one experimental study, administration of progesterone to endometrial cancer cells reduced cancer cell proliferation by activating metabolic regulators known as p21 and p27. In addition, treatment with progesterone led to a reduction in the expression of several cellular adhesion molecules that cancer cells use to attach to normal tissues and spread (Dai 2002). In one study that followed 12 women with stage I, grade 1 endometrial cancer for up to 36 months, placing a progesterone-containing intrauterine device resulted in negative biopsies at 12 months in 6 of 8 patients (Montz 2002).

An experimental study using endometrial cancer cells found that progesterone augmented the anti-tumor effects of vitamin D by upregulating the expression of vitamin D’s target, the vitamin D receptor (Lee 2013). In another laboratory study, simultaneous administration of a metabolically active form of vitamin D (ie, 1,25-dihydroxyvitamin D3) and progesterone led to a significant upregulation of proteins that help restrain tumor growth and metastasis in endometrial cancer cells (Nguyen 2011). These intriguing results suggest that women undergoing progesterone therapy for endometrial cancer may be able to achieve a more desirable outcome by ensuring their blood levels of 25-hydroxyvitamin D are in the optimal range, although studies have yet to test this hypothesis.