Papillary Serous Endometrial Carcinoma

Papillary serous endometrial carcinoma is a rare but aggressive form of uterine cancer that requires early detection and comprehensive treatment. Though it accounts for only about 10% of endometrial cancer cases, it is responsible for approximately 40% of deaths from this disease.

Table of contents

• What is papillary serous endometrial carcinoma?
• Other names for this cancer
• Who is most at risk?
• Symptoms to watch for
• How doctors diagnose this cancer
• Understanding cancer stages
• Why this cancer is different
• What to expect: Survival and outcomes
• Treatment options
• The role of genetic changes
• The precursor condition
• Family connections
• Life after treatment

What is papillary serous endometrial carcinoma?

Papillary serous endometrial carcinoma is a rare and aggressive form of cancer that develops in the endometrium, which is the lining of the uterus^[1]. This cancer accounts for about 5 to 10% of all endometrial cancer cases^[1][4]. Despite being relatively uncommon, it is responsible for about 40% of deaths from endometrial cancer^[1][5].

This type of cancer is classified as a type II endometrial cancer^[3]. It behaves differently from the more common type I endometrial cancers. The cancer tends to spread quickly beyond the uterus and may come back after treatment, even when doctors detect it early^[1].

Other names for this cancer

Uterine papillary serous carcinoma, UPSC, Endometrial serous carcinoma, Uterine serous carcinoma, USC

Who is most at risk?

Papillary serous endometrial carcinoma typically occurs in women who are past menopause (the time when menstrual periods have stopped)^[1]. The disease is more common in Black women, women of normal weight, and those who are postmenopausal^[1].

The average age at diagnosis is around 62 to 67 years^[3][14]. Unlike the more common type of endometrial cancer, women with this disease do not necessarily have a higher body weight^[14].

Symptoms to watch for

The most common symptom of papillary serous endometrial carcinoma is bleeding after menopause^[1][3]. Any vaginal bleeding that occurs after menopause should be evaluated by a doctor, as it may be a sign of this or other types of uterine cancer.

Other symptoms that women with this cancer may experience include^[1][4]:

• Pain during sexual intercourse
• Pain in the pelvic area
• Unexplained weight loss
• Abnormal results on a Pap test during a regular gynecological exam

In more advanced stages, when the cancer has spread beyond the uterus, symptoms may also include^[4]:

• Painful urination
• Changes in bowel habits
• A swollen stomach or bloating
• Cough (if the cancer has spread to the lungs)

How doctors diagnose this cancer

To diagnose papillary serous endometrial carcinoma, doctors use several approaches. A common method is taking a small sample of tissue from the endometrium, called a biopsy, to test for cancer cells^[1]. However, these biopsies are not always effective at detecting this particular type of cancer^[1].

Another diagnostic tool is pelvic ultrasound, which is an imaging scan that measures the thickness of the uterine lining^[1]. An abnormally thick stripe in the uterus may indicate a problem that requires further investigation.

Women with this cancer often do not notice symptoms until the disease has already spread beyond the uterus^[1]. About half of all women diagnosed with papillary serous endometrial carcinoma have stage 3 or 4 cancer, meaning the disease has already spread to nearby tissues or distant parts of the body^[4].

Understanding cancer stages

Papillary serous endometrial carcinoma is staged at the time of surgery using a system developed by the International Federation of Gynecology and Obstetrics^[3]. The stages are defined as follows:

• Stage IA: The tumor is limited to less than half of the myometrium (the muscular wall of the uterus)
• Stage IB: The tumor has invaded more than half of the myometrium
• Stage II: The cancer has spread to the cervical stroma (the tissue of the cervix)
• Stage IIIA: The tumor has spread to the outer surface of the uterus or to the fallopian tubes and ovaries
• Stage IIIB: The cancer has spread to the vagina or tissues around the uterus
• Stage IIIC1: The cancer has spread to pelvic lymph nodes
• Stage IIIC2: The cancer has spread to para-aortic lymph nodes (nodes near the main artery of the body)
• Stage IVA: The tumor has invaded the bladder or bowel
• Stage IVB: The cancer has spread to distant parts of the body, including lymph nodes in the abdomen or groin

At least 37% of cases that show no invasion in the uterus are found to have stage III or IV disease after comprehensive surgical staging^[2]. This highlights how aggressively this cancer spreads, even when it appears limited at first.

Why this cancer is different

Unlike the more common type of endometrial cancer, papillary serous endometrial carcinoma does not depend on the hormone estrogen to grow^[3][4]. Most endometrial cancers develop in women who have been exposed to higher levels of estrogen over their lifetime. Factors that raise estrogen levels include having a higher body weight, starting menstruation early, and taking certain medications.

However, papillary serous endometrial carcinoma develops even in women without these common risk factors^[4]. It arises in the setting of endometrial atrophy (thinning of the uterine lining) rather than the thickening seen in other types of endometrial cancer^[3]. This makes it a fundamentally different disease that requires different approaches to treatment.

What to expect: Survival and outcomes

Papillary serous endometrial carcinoma is typically classified as a high-grade cancer, meaning the cells look very abnormal under a microscope and the cancer tends to be more aggressive^[4]. Women with this cancer are 2.5 times more likely to be diagnosed at a more advanced stage compared to other types of endometrial cancer^[4].

Survival rates vary significantly based on the stage at diagnosis. According to data published in 2009, five-year survival rates are^[3]:

• Stage I: 50% to 80%
• Stage II: 50%
• Stage III: 20%
• Stage IV: 5% to 10%

More recent studies have shown somewhat improved outcomes. One study of 138 women found that 42% were disease-free at five years^[3]. For women who truly have disease confined to the uterus after comprehensive surgical staging, especially those with stage IA disease with minimal invasion, outcomes have been good to excellent^[2].

However, for patients with stage III or IV disease, outcomes remain poor regardless of the type of additional treatment received^[2]. These findings highlight the critical importance of detecting the disease as early as possible.

Treatment options

Surgery

The primary treatment for papillary serous endometrial carcinoma is surgery^[1][3]. Women often undergo a procedure called laparotomy, in which the surgeon opens the abdomen to examine the organs around the uterus and determine how much the cancer has spread^[1]. This process is called staging the tumor.

The surgical treatment typically includes^[1][3]:

• Hysterectomy to remove the uterus
• Removal of both fallopian tubes and ovaries
• Removal of any visible tissue affected by cancer
• Removal of lymph nodes for testing
• Removal of the omentum (a fold of tissue in the abdomen)

During surgery, doctors may also perform a pelvic wash, in which they rinse the inside of the pelvis with saline solution that is then collected and tested for cancer cells^[1]. In stage II cancer, surgeons may also remove the cervix and upper part of the vagina^[1].

Radiation therapy

After surgery, papillary serous endometrial carcinoma is often treated with radiation therapy, chemotherapy, or both^[1]. Radiation is used to treat localized cancer or to prevent the cancer from coming back. However, it is not very effective as a stand-alone treatment^[1].

Doctors may use external beam radiation, which directs radiation from outside the body, or brachytherapy, which involves placing a tiny radioactive cylinder inside the vagina to kill cancer cells^[1]. Sometimes doctors use a combination of both approaches.

Chemotherapy

Even in early stages of papillary serous endometrial carcinoma, doctors often recommend chemotherapy to kill any cancer cells that may remain in the body after surgery^[1]. The drugs most commonly used to treat early-stage disease include cisplatin and carboplatin combined with paclitaxel^[1].

Sometimes doctors suggest chemotherapy and radiation at the same time, or patients may receive cycles of both treatments^[1].

Targeted therapy

In about 30% to one-third of women with papillary serous endometrial carcinoma, a gene called HER2/neu makes too many copies of itself^[1][9]. This genetic change can fuel the growth of cancer cells.

A drug called trastuzumab (Herceptin) targets HER2/neu and blocks it^[1]. This drug has been used to treat breast cancer with high HER2 levels since 1998^[9]. In clinical trials for uterine serous carcinoma, when researchers combined trastuzumab with regular chemotherapy, women lived longer without their cancer getting worse^[1][9].

Women who received trastuzumab plus standard chemotherapy lived an average of 13 months before their cancer started growing again, compared to 8 months for those who received chemotherapy alone^[9]. Overall survival was also longer: 29.6 months with trastuzumab versus 24.4 months without it^[9].

Researchers are also studying other targeted drugs. Pertuzumab (Perjeta) blocks even more pathways involved in this cancer than trastuzumab^[1]. Lapatinib (Tykerb) blocks HER2 and may reduce the growth of malignant tumors^[1].

The role of genetic changes

Several genetic changes are involved in the development of papillary serous endometrial carcinoma. The most important is a mutation in the TP53 gene, which is a tumor suppressor gene that normally helps prevent cancer^[3]. This mutation is found even in precursor lesions, suggesting that changes in this gene occur early in the disease process^[3].

Many other mutations have been identified, including changes in the PI3K and PP2A genes^[3]. Several important markers have also been identified, including p53, HER2/neu, IL-6, kallikrein 6, and claudin-4^[6]. Some of these markers may be targets for new treatments.

If a woman is diagnosed with endometrial cancer, her doctor may check the cancer cells for these genetic mutations. These changes can help doctors understand how the cancer behaves and which treatments might work best^[4].

The precursor condition

Before papillary serous endometrial carcinoma develops, there is often a precursor condition called serous endometrial intraepithelial carcinoma^[3][6]. This condition has been recognized as an early form of the disease^[6].

The recognition of this precursor lesion raises the possibility that doctors might one day be able to prevent papillary serous endometrial carcinoma by identifying and treating women with this early change before it develops into invasive cancer^[2].

Family connections

Several gene mutations may be more common in women with papillary serous endometrial carcinoma^[1]. Women with this cancer are more likely to have relatives who have endometrial cancer, ovarian cancer, and especially pancreatic cancer^[1].

This suggests that some cases of papillary serous endometrial carcinoma may run in families. If you have been diagnosed with this cancer, it may be helpful to discuss your family history with your doctor.

Life after treatment

After treatment for papillary serous endometrial carcinoma, women need to see their doctor regularly for follow-up visits^[1]. These visits are important for checking whether the cancer has come back and for managing any side effects from treatment.

The specific schedule for follow-up appointments will depend on the stage of cancer at diagnosis and the types of treatment received. Your healthcare team will provide guidance on how often you need to be seen and what tests may be needed during follow-up.