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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Most of the women who develop DCIS do not experience any symptoms. The majority of cases (80-85%) are detected through screening mammography. The first signs and symptoms may appear if the cancer advances. Because of the lack of early symptoms, DCIS is most often detected at screening mammography.
In a few cases, DCIS may cause:
- A lump or thickening in or near the breast or under the arm
- A change in the size or shape of the breast
- Nipple discharge or nipple tenderness; the nipple may also be inverted, or pulled back into the breast
- Ridges or pitting of the breast; the skin may look like the skin of an orange
- A change in the way the skin of the breast, areola, or nipple looks or feels such as warmth, swelling, redness or scaliness.
The first noticeable symptom of breast cancer is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump. The earliest breast cancers are detected by a mammogram. Lumps found in lymph nodes located in the armpits can also indicate breast cancer.
Indications of breast cancer other than a lump may include thickening different from the other breast tissue, one breast becoming larger or lower, a nipple changing position or shape or becoming inverted, skin puckering or dimpling, a rash on or around a nipple, discharge from nipple/s, constant pain in part of the breast or armpit, and swelling beneath the armpit or around the collarbone. Pain ("mastodynia") is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.
Inflammatory breast cancer is a particular type of breast cancer which can pose a substantial diagnostic challenge. Symptoms may resemble a breast inflammation and may include itching, pain, swelling, nipple inversion, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as "peau d'orange". As inflammatory breast cancer does not present as a lump there can sometimes be a delay in diagnosis.
Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as skin changes resembling eczema, such as redness, discoloration, or mild flaking of the nipple skin. As Paget's disease of the breast advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's disease of the breast also have a lump in the breast.
In rare cases, what initially appears as a fibroadenoma (hard, movable non-cancerous lump) could in fact be a phyllodes tumor. Phyllodes tumors are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumors are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline, or malignant.
Occasionally, breast cancer presents as metastatic disease—that is, cancer that has spread beyond the original organ. The symptoms caused by metastatic breast cancer will depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally signal breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are called "non-specific", meaning they could be manifestations of many other illnesses.
Most symptoms of breast disorders, including most lumps, do not turn out to represent underlying breast cancer. Fewer than 20% of lumps, for example, are cancerous, and benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. Nevertheless, the appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.
Like many malignancies, penile cancer can spread to other parts of the body. It is usually a primary malignancy, the initial place from which a cancer spreads in the body. Much less often it is a secondary malignancy, one in which the cancer has spread to the penis from elsewhere. The staging of penile cancer is determined by the extent of tumor invasion, nodal metastasis, and distant metastasis.
The T portion of the AJCC TNM staging guidelines are for the primary tumor as follows:
- TX: Primary tumor cannot be assessed.
- T0: No evidence of primary tumor.
- Tis: Carcinoma "in situ".
- Ta: Noninvasive verrucous carcinoma.
- T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3–4).
- T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated.
- T2: Tumor invades the corpus spongiosum or cavernosum.
- T3: Tumor invades the urethra or prostate.
- T4: Tumor invades other adjacent structures.
Anatomic Stage or Prognostic Groups of penile cancer are as follows:
- Stage 0—Carcinoma "in situ".
- Stage I—The cancer is moderately or well differentiated and only affects the subepithelial connective tissue.
- Stage II—The cancer is poorly differentiated, affects lymphatics, or invades the corpora or urethra.
- Stage IIIa—There is deep invasion into the penis and metastasis in one lymph node.
- Stage IIIb—There is deep invasion into the penis and metastasis into multiple inguinal lymph nodes.
- Stage IV—The cancer has invaded into structures adjacent to the penis, metastasized to pelvic nodes, or distant metastasis is present.
Penile cancer is a malignant growth found on the skin or in the tissues of the penis. Around 95% of penile cancers are squamous cell carcinomas. Other types of penile cancer such as Merkel cell carcinoma, small cell carcinoma, melanoma and other are generally rare.
Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of the breast. DCIS is classified as Stage 0. It rarely produces symptoms or a breast lump one can feel, and is usually detected through screening mammography.
In DCIS, abnormal cells are found in the lining of one or more milk ducts in the breast. "In situ" means "in place" and refers to the fact that the abnormal cells have not moved out of the mammary duct and into any of the surrounding tissues in the breast ("pre-cancerous" refers to the fact that it has not yet become an invasive cancer). In some cases, DCIS may become invasive and spread to other tissues, but there is no way of determining which lesions will remain stable without treatment, and which will go on to become invasive. DCIS encompasses a wide spectrum of diseases ranging from low-grade lesions that are not life-threatening to high-grade (i.e. potentially highly aggressive) lesions.
DCIS has been classified according to the architectural pattern of the cells (solid, cribriform, papillary, and micropapillary), tumor grade (high, intermediate, and low grade), and the presence or absence of comedo histology. DCIS can be detected on mammograms by examining tiny specks of calcium known as microcalcifications. Since suspicious groups of microcalcifications can appear even in the absence of DCIS, a biopsy may be necessary for diagnosis.
About 20–30% of those who do not receive treatment develop breast cancer. It is the most common type of pre-cancer in women. There is some disagreement as to whether, for statistical purposes, it should be counted as a cancer: some include DCIS when calculating breast cancer statistics while others do not.
Symptoms are very variable and may not be present at all in "occult inflammatory breast cancer". Quick onset of symptoms is typical, the breast often looks swollen and red, or “inflamed”, sometimes overnight, and are easy to misdiagnose as mastitis. Invasion of the local lymphatic ducts impairs drainage and causes edematous swelling of the breast. Because the skin of the breast is tethered by the suspensory ligament of Cooper, the accumulation of fluid may cause the skin of the breast to assume a dimpled appearance similar to an orange peel (peau d'orange). A palpable tumor is frequently not obvious as in other forms of breast cancer.
Symptoms may include:
- Sudden swelling of the breast
- Skin changes on breast
- Reddened area with texture resembling the peel of an orange (peau d’orange)
- Nipple retraction (flattened look) or discharge
- Pain in the breast
- Itching of breast
- Swelling of lymph nodes under the arm or in the neck
- Unusual warmth of the affected breast
- Breast is harder or firmer
Other symptoms may rarely include:
- Swelling of the arm
- Breast size may decrease instead of increasing
- Although a dominant mass is present in many cases, most inflammatory cancers present as diffuse infiltration of the breast without a well-defined tumor.
- A lump may become present and grow rapidly
Most patients do not experience all the symptoms of IBC. Not all symptoms need to be present in order to be diagnosed.
Inflammatory breast cancer is one of the most aggressive types of breast cancer that can occur in women of any age (and,
extremely rarely, in men). It is called inflammatory because it frequently presents with symptoms resembling an inflammation. Despite the name, whether inflammation contributes to the development of "inflammatory breast cancer" remains an area of ongoing research. However it can present with very variable signs and symptoms, frequently without detectable tumors and therefore is often not detected by mammography or ultrasound.
Typical presentation is rapid swelling, sometimes associated by skin changes (peau d'orange), and nipple retraction. Other symptoms include rapid increase in breast size, redness, persistent itching, skin hot to touch. IBC often initially resembles mastitis.
Only about 50-75% cases have the typical presentation. Symptoms can be completely atypical such as acute central venous thrombosis as the sole presenting symptom.
IBC makes up only a small percentage of breast cancer cases (1-6% in the USA). IBC is often diagnosed in younger women although average age of presentation does not differ much from other kinds of breast cancer (average age 57 years). African-Americans are usually diagnosed at younger ages than Caucasian women, and also have a higher risk of getting IBC. Recent advances in therapy have improved the prognosis considerably and at least one third of women will survive the diagnosis by 10 years or longer.
Male breast cancer (male breast neoplasm) is a rare cancer in males that originates from the breast. Many males with breast cancer have inherited a "BRCA" mutation, but there are other causes, including alcohol abuse and exposure to certain hormones and ionizing radiation.
As it presents a similar pathology as female breast cancer, assessment and treatment relies on experiences and guidelines that have been developed in female patients. The optimal treatment is currently not known.
In many cases, ductal carcinoma is asymptomatic, and detected as abnormal results on mammography. When symptoms occur, a painless, enlarging mass that does not fluctuate with the menstrual period may be felt. Pinching of the overlying skin may also be seen. Certain subtypes, such as inflammatory carcinomas, may result in a swollen, enlarged and tender breast. All variants of cancer, if there is metastatic spread, may cause enlarged lymph nodes and affect other organs.
Invasive carcinoma of no special type (NST) is the most common form of invasive breast cancer. It accounts for 55% of breast cancer incidence upon diagnosis, according to statistics from the United States in 2004. On a mammogram, it is usually visualized as a mass with fine spikes radiating from the edges. On physical examination, this lump usually feels much harder or firmer than benign breast lesions such as fibroadenoma. On microscopic examination, the cancerous cells invade and replace the surrounding normal tissues. IDC is divided in several histological subtypes.
As in females, infiltrating ductal carcinoma is the most common type. While intraductal cancer, inflammatory carcinoma, and Paget's disease of the nipple have been described, lobular carcinoma in situ has not been seen in males. Breast cancer in males spreads via lymphatics and blood stream like female breast cancer. Accordingly, the TNM staging system for breast cancer is the same for males and females.
Size of the lesion and lymph node involvement determine prognosis; thus small lesions without lymph node involvement have the best prognosis. Estrogen receptor and progesterone receptor status and HER2/neu (Human Epidermal Growth Factor Receptor 2) gene amplification need to be reported as they may affect treatment options. About 85% of all male breast cancers are estrogen receptor–positive, and 70% are progesterone receptor–positive.
Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in cough or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may produce observable lumps. Ulceration can cause bleeding that, if it occurs in the lung, will lead to coughing up blood, in the bowels to anemia or rectal bleeding, in the bladder to blood in the urine and in the uterus to vaginal bleeding. Although localized pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause a buildup of fluid within the chest or abdomen.
Triple-negative breast cancer (sometimes abbreviated TNBC) refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. This makes it more difficult to treat since most hormone therapies target one of the three receptors, so triple-negative cancers often require combination therapies. Triple negative is sometimes used as a surrogate term for basal-like; however, more detailed classification may provide better guidance for treatment and better estimates for prognosis.
Triple-negative breast cancers comprise a very heterogeneous group of cancers. There are conflicting information over prognosis for the various subtypes but it appears that the Nottingham prognostic index is valid and hence general prognosis is rather similar with other breast cancer of same stage, except that more aggressive treatment is required. Some types of triple-negative breast cancer are known to be more aggressive with poor prognosis, while other types have very similar or better prognosis than hormone receptor positive breast cancers. Pooled data of all triple-negative subtypes suggest that with optimal treatment 20-year survival rates are very close to those of hormone positive cancer.
Triple-negative breast cancers have a relapse pattern that is very different from hormone-positive breast cancers: the risk of relapse is much higher for the first 3–5 years but drops sharply and substantially below that of hormone-positive breast cancers after that. This relapse pattern has been recognized for all types of triple-negative cancers for which sufficient data exists although the absolute relapse and survival rates differ across subtypes.
When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancer's type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer is a "great imitator". Thus, it is common for people diagnosed with cancer to have been treated for other diseases, which were hypothesized to be causing their symptoms.
People may become anxious or depressed post-diagnosis. The risk of suicide in people with cancer is approximately double.
The symptoms produced by metastatic breast cancer vary by the location of the metastases. For instance:
- Metastatic disease to the bone causes severe, progressive pain, and, less commonly, pathological fracture, erythema over the affected bone, and swelling.
- Metastatic breast cancer to the brain causes the following symptoms: persistent, progressively worsening headache, visual changes, seizures, nausea or vomiting, vertigo, behavioral and personality changes, and increased intracranial pressure.
- Metastatic disease to the liver causes jaundice, elevated liver enzymes, abdominal pain, loss of appetite, nausea, and vomiting
- Metastatic breast cancer to the lung or pleura causes chronic cough, dyspnea, abnormal chest X-ray, and chest pain.
- Other nonspecific systemic symptoms of metastatic breast cancer include fatigue, malaise, weight loss, and poor appetite.
Bladder cancer characteristically causes blood (redness) in the urine. This blood in the urine may be visible to the naked eye (gross/macroscopic hematuria) or detectable only by microscope (microscopic hematuria). Hematuria is the most common symptom in bladder cancer. It occurs in approximately 80–90% of the patients.
Other possible symptoms include pain during urination, frequent urination, or feeling the need to urinate without being able to do so. These signs and symptoms are not specific to bladder cancer, and are also caused by non-cancerous conditions, including prostate infections, over-active bladder and cystitis. There are many other causes of hematuria, such as bladder or ureteric stones, infection, kidney disease, kidney cancers and vascular malformations.
Patients with advanced disease refer pelvic or bony pain, lower-extremity edema, or flank pain.
Rarely a palpable mass can be detected on physical examination.
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, fluid coming from the nipple, or a red scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.
Risk factors for developing breast cancer include being female, obesity, lack of physical exercise, drinking alcohol, hormone replacement therapy during menopause, ionizing radiation, early age at first menstruation, having children late or not at all, older age, and family history. About 5–10% of cases are due to genes inherited from a person's parents, including BRCA1 and BRCA2 among others. Breast cancer most commonly develops in cells from the lining of milk ducts and the lobules that supply the ducts with milk. Cancers developing from the ducts are known as ductal carcinomas, while those developing from lobules are known as lobular carcinomas. In addition, there are more than 18 other sub-types of breast cancer. Some cancers, such as ductal carcinoma in situ, develop from pre-invasive lesions. The diagnosis of breast cancer is confirmed by taking a biopsy of the concerning lump. Once the diagnosis is made, further tests are done to determine if the cancer has spread beyond the breast and which treatments it may respond to.
The balance of benefits versus harms of breast cancer screening is controversial. A 2013 Cochrane review stated that it is unclear if mammographic screening does more good or harm. A 2009 review for the US Preventive Services Task Force found evidence of benefit in those 40 to 70 years of age, and the organization recommends screening every two years in women 50 to 74 years old. The medications tamoxifen or raloxifene may be used in an effort to prevent breast cancer in those who are at high risk of developing it. Surgical removal of both breasts is another preventative measure in some high risk women. In those who have been diagnosed with cancer, a number of treatments may be used, including surgery, radiation therapy, chemotherapy, hormonal therapy and targeted therapy. Types of surgery vary from breast-conserving surgery to mastectomy. Breast reconstruction may take place at the time of surgery or at a later date. In those in whom the cancer has spread to other parts of the body, treatments are mostly aimed at improving quality of life and comfort.
Outcomes for breast cancer vary depending on the cancer type, extent of disease, and person's age. Survival rates in the developed world are high, with between 80% and 90% of those in England and the United States alive for at least 5 years. In developing countries survival rates are poorer. Worldwide, breast cancer is the leading type of cancer in women, accounting for 25% of all cases. In 2012 it resulted in 1.68 million new cases and 522,000 deaths. It is more common in developed countries and is more than 100 times more common in women than in men.
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.
In the most specific usage (narrowest sense), the glandular origin or traits are exocrine; endocrine gland tumors, such as a VIPoma, an insulinoma, or a pheochromocytoma, are typically not referred to as adenocarcinomas but rather are often called neuroendocrine tumors. Epithelial tissue sometimes includes, but is not limited to, the surface layer of skin, glands, and a variety of other tissue that lines the cavities and organs of the body. Epithelial tissue can be derived embryologically from any of the germ layers (ectoderm, endoderm, or mesoderm). To be classified as adenocarcinoma, the cells do not necessarily need to be part of a gland, as long as they have secretory properties. Adenocarcinoma is the malignant counterpart to adenoma, which is the benign form of such tumors. Sometimes adenomas transform into adenocarcinomas, but most do not.
Well differentiated adenocarcinomas tend to resemble the glandular tissue that they are derived from, while poorly differentiated adenocarcinomas may not. By staining the cells from a biopsy, a pathologist can determine whether the tumor is an adenocarcinoma or some other type of cancer. Adenocarcinomas can arise in many tissues of the body owing to the ubiquitous nature of glands within the body, and, more fundamentally, to the potency of epithelial cells. While each gland may not be secreting the same substance, as long as there is an exocrine function to the cell, it is considered glandular and its malignant form is therefore named adenocarcinoma.
Triple-negative breast cancers (TNBC) are sometimes classified into "basal-type" and other cancers; however, there is no standard classification scheme. Basal type cancers are frequently defined by cytokeratin 5/6 and EGFR staining. However, no clear criteria or cutoff values have been standardized yet. About 75% of basal-type breast cancers are triple negative.
Some TNBC overexpress epidermal growth factor receptor (EGFR) or transmembrane glycoprotein NMB (GPNMB).
Upon histologic examination, triple-negative breast tumors mostly fall into the categories of "secretory cell carcinoma" or "adenoid cystic types" (both considered less aggressive); "medullary cancers" and grade 3 invasive "ductal carcinomas" with no specific subtype; and highly aggressive "metastatic cancers". Medullary TNBC in younger women are frequently "BRCA1"-related.
Rare forms of triple-negative breast cancer are "apocrine" and "squamous carcinoma". "Inflammatory breast cancer" is also frequently triple negative.
Many proteins such as Caveolin 1/2, Survivin are researched as possible classification or prognostic factors.
TNBCs have been classified using an integrative analysis of cancer genomics data (DNA copy number, DNA methylation, and mRNA) and PPI data from a prognostic point of view and several key subnetworks (i.e. ubiquitin/proteasome, complement system, metabolism-related Warburg effect, ER-Golgi-cell surface trafficking, transcription) significantly related to patient survival have been identified.
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom.
All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.
Lobular carcinoma "in situ" (LCIS) is a condition caused by unusual cells in the lobules of the breast.
Many do not consider it cancer, but it can indicate an increased risk of future cancer. The national database registrars, however, consider it a malignancy.
Unlike ductal carcinoma "in situ" (DCIS), LCIS is not associated with calcification, and is typically an incidental finding in a biopsy performed for another reason. LCIS only accounts for about 15% of the "in situ" (ductal or lobular) breast cancers.
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumours, secondaries or stage 4 breast cancer, is a stage of breast cancer where the disease has spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer. There is no stage after IV.
It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer or, rarely, before the primary breast cancer has been diagnosed.
Metastatic breast cancer cells frequently differ from the preceding primary breast cancer in properties such as receptor status. The cells have often developed resistance to several lines of previous treatment and have acquired special properties that permit them to metastasize to distant sites. Metastatic breast cancer can be treated, sometimes for many years, but it cannot be cured. Distant metastases are the cause of about 90% of deaths due to breast cancer.
Breast cancer can metastasize anywhere in body but primarily metastasizes to the bone, lungs, regional lymph nodes, liver and brain, with the most common site being the bone. Treatment of metastatic breast cancer depends on location of the metastatic tumours and includes surgery, radiation, chemotherapy, biological, and hormonal therapy.
Typical environmental barriers in a metastatic event include physical (a basement membrane), chemical (reactive oxygen species or ROS, hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extra-cellular matrix (ECM) peptides) components. Organ-specific anatomic considerations also influence metastasis; these include blood-flow patterns from the primary tumor and the homing ability of cancer cells to certain tissues. The targeting by cancer cells of specific organs is probably regulated by chemo-attractant factors and adhesion molecules produced by the target organ, along with cell-surface receptors expressed by the tumor cells.
Esophageal cancer may be due to either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used.
Ninety percent of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to squamous cell carcinoma.
Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms include blood in the urine, pain with urination, and low back pain.
Risk factors for bladder cancer include smoking, family history, prior radiation therapy, frequent bladder infections, and exposure to certain chemicals. The most common type is transitional cell carcinoma. Other types include squamous cell carcinoma and adenocarcinoma. Diagnosis is typically by cystoscopy with tissue biopsies. Staging of the cancer is typically determined by medical imaging such as CT scan and bone scan.
Treatment depends on the stage of the cancer. It may include some combination of surgery, radiation therapy, chemotherapy, or immunotherapy. Surgical options may include transurethral resection, partial or complete removal of the bladder, or urinary diversion. Typical five-year survival rates in the United States are 77%.
Bladder cancer, as of 2015, affects about 3.4 million people with 430,000 new cases a year. Age of onset is most often between 65 and 85 years of age. Males are more often affected than females. In 2015 it resulted in 188,000 deaths.