Uterine Cancer: Symptoms, Types, Causes and Treatment

Uterine cancer is one of the most common gynecological malignancies, affecting thousands of women worldwide each year. Understanding its symptoms, types, causes, and available treatments can empower women to recognize early warning signs and seek timely medical attention. In this comprehensive guide, we explore the key aspects of uterine cancer, drawing on the latest research and clinical guidelines to provide reliable and up-to-date information.

Symptoms of Uterine Cancer

Uterine cancer, especially in its early stages, often presents with symptoms that can be subtle or mistaken for less serious conditions. Recognizing these symptoms is crucial for early diagnosis and improved outcomes.

Symptom	Frequency/Importance	Patient Population	Source(s)
Abnormal Uterine Bleeding	Most common, early symptom	Pre- & post-menopausal	2 4 5 10
Postmenopausal Bleeding	Very high predictive value	Postmenopausal women	2 4 5 10
Excessive Vaginal Bleeding	Significant risk marker	All ages	2 4
Irregular Menstruation	Notable, especially premenopausal	Younger women	2 4
Vaginal Discharge	Sometimes present	All ages	2
Abdominal/Pelvic Pain	Less specific	All ages	2 5
Fatigue	Common during/after treatment	Diagnosed patients	1 3
Gastrointestinal Symptoms	Nausea, vomiting, diarrhea	During radiotherapy	1
Anemia (Low Hemoglobin)	Associated with bleeding	All ages	2

Table 1: Key Symptoms

Overview of Major Symptoms

Abnormal Uterine Bleeding

• Most common presenting symptom: Over 80% of women with uterine cancer experience some form of abnormal vaginal bleeding, which includes bleeding after menopause, between periods, or unusually heavy periods. This symptom is especially significant in postmenopausal women, for whom any vaginal bleeding should be promptly evaluated 2 4 5 10.
• Specificity and sensitivity: Studies highlight that postmenopausal bleeding has a strong association with uterine cancer, with a positive predictive value of about 4% in primary care 2 4. However, not all abnormal bleeding indicates cancer, so evaluation is necessary.

Other Symptoms

• Excessive or Irregular Bleeding: In premenopausal women, irregular or heavy menstruation can also be a warning sign 2 4.
• Vaginal Discharge: Sometimes, especially in advanced cases, women may notice watery or blood-tinged discharge 2.
• Abdominal and Pelvic Pain: These symptoms are less common and often indicate more advanced disease. Pain, bloating, or a feeling of fullness can occur 2 5.
• Fatigue and Systemic Symptoms: Fatigue is particularly notable during and after treatment, such as radiotherapy, and is closely linked with psychological distress 1 3.
• Gastrointestinal Issues: Side effects of treatment like nausea, vomiting, and diarrhea may also be present 1.
• Anemia: Chronic blood loss can lead to low hemoglobin, resulting in tiredness and weakness 2.

Symptom Patterns and Diagnostic Challenges

• Symptom overlap: Many of these signs overlap with benign gynecological conditions, making awareness and timely evaluation vital 4.
• Disparities: Black women are more likely to present with non-bleeding symptoms and advanced disease, highlighting the need for equitable healthcare and symptom recognition 5.

Types of Uterine Cancer

Uterine cancer is not a single disease but rather a group of malignancies originating from different tissues within the uterus. Understanding these types is vital for determining appropriate treatment and prognosis.

Type	Prevalence	Clinical Features	Source(s)
Endometrial Carcinoma	~95% (most common)	Often early symptoms, better prognosis	6 7 10 14
Uterine Sarcomas	3–7% (rare)	Aggressive, poorer prognosis, diverse subtypes	6 7 8 10
Carcinosarcomas	<5%, very aggressive	Biphasic tumors, poor survival rates	7 8 9
Rare Subtypes (e.g., serous, clear-cell, stromal sarcomas)	<10%	Aggressive course, often advanced at diagnosis	7 8 15

Table 2: Main Types of Uterine Cancer

Classification and Key Differences

Endometrial Carcinoma

• Definition: Originates from the endometrial lining of the uterus 6 10 14.
• Subtypes:
  • Endometrioid: Most common, often estrogen-related.
  • Serous and Clear-Cell: Less common but more aggressive 7 15.
• Demographics: Most frequent in postmenopausal women 10.
• Prognosis: Generally favorable if diagnosed early.

Uterine Sarcomas

• Definition: Malignancies arising from the muscle or connective tissue of the uterus 6 8.
• Subtypes:
  • Leiomyosarcomas: Most prevalent among sarcomas, high-grade and aggressive 8.
  • Endometrial Stromal Sarcomas: Can be low or high grade, with low-grade forms behaving more indolently 8.
  • Adenosarcomas: Usually have a better prognosis unless showing aggressive features 8.
• Features: Typically present at a more advanced stage, poorer prognosis than carcinomas.

Carcinosarcomas (Malignant Mixed Müllerian Tumors)

• Definition: Tumors with both epithelial (carcinoma) and mesenchymal (sarcoma) components, now often classified as metaplastic carcinomas 8 9.
• Clinical Course: Highly aggressive, high risk of metastasis at diagnosis, 5-year survival very poor in advanced stages 9.
• Treatment: Surgery is primary, with variable benefit from chemotherapy and radiation 9.

Rare Subtypes

• Papillary Serous, Clear-Cell Carcinomas, Stromal Sarcomas: These account for a disproportionate share of deaths due to their aggressive nature 7.
• Unique Features: May require specific diagnostic and therapeutic approaches, including targeted therapies for HER2-positive serous carcinomas 15.

Causes of Uterine Cancer

While the precise cause of most uterine cancers remains unclear, research has identified several risk factors that can increase a woman's likelihood of developing the disease.

Cause/Risk Factor	Mechanism/Detail	Population at Risk	Source(s)
Estrogen Exposure	Unopposed estrogen stimulates growth	Obesity, HRT users	10 12
Genetics (e.g., HNPCC)	Inherited mutations (MMR genes)	Families with cancer syndromes	10 12
Age	Incidence rises with age	Postmenopausal women	2 10 12
Radiation Exposure	Increases risk, especially during puberty	History of pelvic radiation	10 13
Tamoxifen Use	Weak estrogenic effect on uterus	Breast cancer patients	10
Other (Diabetes, Hypertension)	Associated metabolic factors	Women with chronic illness	2 12
Molecular Factors (HMGA1, COX-2)	Oncogene activation in tumors	High-grade tumors	11
Unknown/Multifactorial	Most cases	General population	12

Table 3: Main Causes and Risk Factors

Major Risk Factors Explained

Hormonal and Lifestyle Factors

• Estrogen Exposure: Chronic exposure to estrogen without opposition by progesterone is a major driver. This can result from obesity (which increases endogenous estrogen), certain forms of hormone replacement therapy (HRT), late menopause, or early menarche 10 12.
• Tamoxifen: A breast cancer drug that can stimulate the endometrium, increasing risk modestly 10.

Genetics

• Hereditary Nonpolyposis Colorectal Cancer (HNPCC/Lynch Syndrome): Women with this syndrome have a much higher lifetime risk due to mutations in DNA mismatch repair genes 10 12.
• Family History: Suggests possible genetic predisposition even outside known syndromes.

Age and Reproductive History

• Age: Risk increases significantly after menopause, with a median age at diagnosis around 67 years 2 10.
• Nulliparity: Never having given birth increases risk, possibly due to more uninterrupted estrogen exposure 10.

Environmental and Other Medical Factors

• Radiation Exposure: Prior pelvic radiation, particularly during adolescence, raises risk specifically for corpus (not cervical) cancer 10 13.
• Metabolic Conditions: Diabetes, hypertension, and elevated blood glucose or platelets are associated with increased risk 2 12.

Molecular and Genetic Insights

• Oncogenes (HMGA1, COX-2): Overexpression of certain genes can drive tumor development and may serve as markers for aggressive disease 11.
• Multifactorial Etiology: For most cases, no single cause is identified, and it's believed that a combination of genetic, hormonal, and environmental factors contribute 12.

Treatment of Uterine Cancer

Treatment for uterine cancer is highly individualized, depending on the type, stage, and specific patient factors. Advances in surgical techniques, chemotherapy, targeted therapies, and immunotherapy have broadened the options for women diagnosed with this disease.

Treatment Modality	Indication/Role	Special Considerations	Source(s)
Surgery (Hysterectomy)	Primary treatment for early-stage	May include lymph node removal	10 14 17
Radiotherapy	Adjuvant or advanced disease	Side effects: fatigue, GI symptoms	1 14 17
Chemotherapy	Advanced/recurrent/aggressive types	Often combined with radiation	9 14 17
Targeted Therapy	HER2-positive, recurrent disease	Trastuzumab, Lenvatinib, etc.	15 16 18
Immunotherapy	Recurrent or advanced disease	Pembrolizumab, clinical trials	16 18
Hormonal Therapy	Select cases, fertility-sparing	Progestins, Tamoxifen	17
Supportive Care	Symptom control, quality of life	Fatigue, psychological support	1 3

Table 4: Main Treatment Options

Primary and Adjuvant Treatments

Surgery

• Hysterectomy (removal of the uterus) is the cornerstone of treatment for most early-stage uterine cancers. The ovaries and fallopian tubes are often removed as well. Lymph node evaluation may be performed to assess spread 10 14 17.
• Fertility-Sparing Approaches: In select young women with early-stage, low-grade endometrial cancer, hormonal treatment with close monitoring may be considered 17.

Radiotherapy

• Role: Used as adjuvant therapy following surgery in women with high-risk features, or as primary therapy in non-surgical candidates 1 14 17.
• Side Effects: Fatigue (often significant), gastrointestinal symptoms such as nausea, vomiting, and diarrhea, and reduced quality of life during treatment 1 3.

Chemotherapy

• Indications: Especially important for advanced, recurrent, or aggressive subtypes like carcinosarcoma and serous carcinoma 9 14 17.
• Regimens: Combination therapies (e.g., carboplatin and paclitaxel) are common; may be combined with radiotherapy or targeted agents 15 18.
• For Carcinosarcoma: Chemotherapy, alone or with radiation, improves outcomes in advanced disease, but overall survival remains poor 9.

Targeted Therapy and Immunotherapy

• HER2-Targeted Therapy: Trastuzumab has shown improved survival in HER2-positive uterine serous carcinoma when added to chemotherapy 15 18.
• Immunotherapy: Agents like pembrolizumab and lenvatinib are now available for advanced or recurrent endometrial cancer, especially those with certain genetic alterations (e.g., mismatch repair deficiency) 16 18.
• Ongoing Clinical Trials: New immunotherapy agents and combinations are under investigation, with promising early results 16.

Hormonal Therapy

• Use: Selected for low-grade, hormone receptor-positive tumors, particularly for women seeking to preserve fertility 17.
• Agents: Progestins are most commonly used.

Supportive Care and Quality of Life

• Fatigue Management: Fatigue, both from disease and its treatment, is a major concern. Psychological support and coping resources are crucial for maintaining quality of life 1 3.
• Symptom Control: Management of side effects (e.g., gastrointestinal symptoms, anemia) is important for treatment adherence and well-being 1 3.

Conclusion

Uterine cancer is a complex disease with diverse symptoms, types, causes, and treatments. Early recognition and prompt evaluation of symptoms, especially abnormal uterine bleeding, are vital for timely diagnosis and improved survival. Advances in molecular understanding and treatment options continue to improve outcomes for many women.

Summary of Key Points:

• Abnormal vaginal bleeding is the most common and important symptom; prompt evaluation is essential, especially in postmenopausal women.
• Uterine cancer includes several types, with endometrial carcinoma being most common and sarcomas/carcinosarcomas being rare but aggressive.
• Major risk factors include estrogen exposure, older age, genetics (e.g., HNPCC), obesity, and prior radiation.
• Treatment is tailored to cancer type and stage, and may include surgery, radiation, chemotherapy, targeted therapy, and immunotherapy.
• Fatigue, psychological distress, and gastrointestinal symptoms are common during treatment, and supportive care is crucial for quality of life.
• New therapies, particularly for advanced and recurrent disease, offer hope for improved survival.

Empowering women with knowledge about uterine cancer can lead to earlier detection, better treatment outcomes, and improved quality of life. If you or someone you know is experiencing unexplained vaginal bleeding or other concerning symptoms, seeking medical advice promptly is the first and most important step.