GYNECOLOGIC ONCOLOGY
UTERINE CANCER
Uterine cancer, as the name indicates, develops from the cells of the uterus - the organ above the vagina and cervix, where pregnancies are carried out. Because it needs to allow for room so the fetus can grow, the uterus is hollow and very flexible. Uterine tissue consists essentially of three layers, which together make up the wall of the uterus. The endometrium is the inner layer of the uterus, which is built up every month and subsequently shed during the menstrual period if no pregnancy occurs. If a pregnancy is started, the endometrium is where the blastocyst (the growing zygote) implants and develops into a fetus. It consists of glandular tissue that can secrete substances into the uterus. The myometrium is the thick middle layer of the uterus, which is made of strong yet stretchable smooth muscle lending support to the uterus. The perimetrium (also called serosa) is the outer layer of the uterus that separates the uterus from other organs in the perineum (the abdominal cavity). It can also secrete substances into the perineum to help keep the uterus smooth and avoid friction with other structures. Like all cancers, uterine cancer grows when uterine cells mutate faster than the immune system can eliminate them, thereby growing into dysfunctional masses. Not all uterine masses are cancerous, however. Most uterine growths, in fact, such as uterine fibroids and other benign cysts, are not invasive and cancerous (meaning, they do not infiltrate other, healthy, tissues). There are two main types of uterine cancer. Endometrial carcinoma, also called adenocarcinoma of the uterus, grows from the cells of the endometrium (the inner lining of the uterus). It makes up for the vast majority (as much as 90 %) of uterine cancers. Uterine sarcoma is a rare (prevalence of 10% or less) but very aggressive type of cancer, that tends to develop from the myometrium (the muscular middle layer of the uterine wall), but can also develop from the glands of the endometrium or other supportive tissues. In either case, it is important to recognize the symptoms of uterine cancer and be aware of risk factors, so that a diagnosis can be made as early as possible.
Risk Factors
The causes of uterine cancer, like many cancers, are presently not well understood. However, there are certain risk factors which increase the likelihood that someone will develop uterine cancer. For instance, obesity has been identified as one of the major risk factors for uterine cancer (in fact, it may account for as much as 50% of cases), and from a population health perspective there seems to be a clear correlation between increased obesity rates and uterine cancer rates. Other risk factors include age, a history of prior cancer diagnoses or higher exposure to female reproductive hormones (particularly estrogen and progesterone), for instance due to early onset of the period (menarche), hormone therapy (such as infertility or menopause treatments, that is hormone therapy which increases hormone activity) or taking certain cancer therapies (such as tamoxifen, which reduces estrogen receptor activity in breast cells but paradoxically increases estrogen receptor activity in uterine cells).
Symptoms
The symptoms of uterine cancer are highly nonspecific. Therefore, it is important to follow up with diagnostic testing when any suspicious symptoms are experienced. Symptoms of uterine cancer include irregular vaginal bleeding and serious pelvic pain. Because these symptoms are so generic and could be the result of a variety of underlying causes, they in themselves should not give rise to concern or panic, but they should lead to timely follow up with a healthcare provider, including a physical exam, pap smear, and imaging as necessary (see below).
Diagnosis
If there are symptoms of pelvic pain and vaginal bleeding, a doctor will perform a pelvic exam, either with or without hysteroscope. During this, a pap smear can be performed, which may sometimes (but not reliably) contain endometrial cells. If endometrial cells are present in the pap smear, a histological exam may show whether or not they are abnormal. If the pelvic exam is otherwise suspicious, imaging should furthermore be performed to visualize any possible masses. This can be done with ultrasound (abdominal or transvaginal), CT (computed tomography), MRI (magnetic resonance imaging), or PET (positron emission tomography). If upon imaging the visualized mass seems suspicious for cancer, a biopsy will be obtained - that is a tissue sample is removed for histological exam (a cellular analysis to identify whether the uterine cells are normal or cancerous). This can be done by a traditional biopsy, which is usually performed as an outpatient procedure without anesthesia and at a regular doctor's office. If the results of the biopsy are inconclusive, or insufficient amounts of cell samples were removed, a more invasive procedure - called dilation and curettage - may be necessary. During this procedure, which is usually performed under general anesthesia and often together with a hysteroscopy (visualization of the inside of the uterus with a small light and lens), a greater sample of uterine cells is shaved off the uterine wall for analysis. A histological exam after biopsy (or dilation and curettage) is the only way to conclusively establish the identity of the uterine cells and come to a reliable diagnosis - which will allow timely start of treatment.
Treatments
Therapies for uterine cancer are similar to those for breast cancer and other gynecologic cancers. Surgery is often necessary to treat uterine cancer. Because uterine cancer grows out of and into the uterine wall, a hysterectomy (removal of the uterus) is often necessary, not uncommonly together with a removal of the fallopian tubes and ovaries as well. If the hysterectomy includes removal of the ovaries, this will not only make the patient infertile, but also induce menopause (because without the ovaries, there will be no more estrogen and progesterone produced). If young women are affected by uterine cancer, it may be attempted to save the uterus (and preserve fertility) by using alternative treatments such as radiation therapy. Radiation can be used before removal of the cancer to shrink the mass and make it more easily removable, after surgery (hysterectomy) to prevent recurrence of the cancer, or alternative to surgery (if surgery is not possible). Chemotherapy is also a common form of treatment, either neoadjuvant (before surgery) or adjuvant (after surgery). Similarly, hormone therapy is often used as a complement to chemotherapy to reduce blood hormone levels and/or block the hormone receptors on the uterine cells. Targeted treatments, such as anti-angiogenic therapy, are aimed at impairing specific pathways, such as the production of new blood vessels in the vicinity of the cancer, in an attempt to destroy cancer cells by depriving them of nutrients necessary for their metabolism and replication. Furthermore, immunotherapy treatments are currently under development (and some, such as Pembrolizumab, have been already FDA approved for aggressive types of uterine cancer) to improve the immune system's response to and destruction of cancer cells.