Prostate Cancer

The prostate is a walnut-sized gland located in front of the rectum and just below the bladder. Although the prostate is made up of several cell types, almost all prostate cancers develop in the glandular cells.2 Cancer of gland cells is known as adenocarcinoma.

The glandular cells of the prostate normally make a fluid that is released into the urethra during ejaculation. This fluid forms part of the seminal fluid, which nourishes the sperm. Secretions from the prostate increase the pH of the semen and help to neutralize the acidity of the female vagina.

The prostate is surrounded by blood and lymphatic vessels:

• Blood vessels are part of the circulatory system. They supply oxygen and nutrients and remove waste from the cells of the prostate.
• Lymphatic vessels are part of a large network termed the lymphatic systemA large network of vessels that carry fluid and cells of the immune system around the body. Lymph nodes are regional collection centers in the lymphatic system. Fluid from the areas surrounding the lymph nodes drains into the lymph nodes. Cells from Tumor cells may break away from the primary tumor and be carried to a nearby lymph node. The lymphatic system is a primary mechanism for tumors to move, or metastasize, to other parts of the body.. These vessels collect and carry fluid and cells from the tissues of the body. Smaller lymphatic vessels merge with larger ones, as streams merge into a river. Large vessels empty into grape-like clusters of lymphatic tissue called lymph nodesA grape-like cluster of lymphatic tissue. Lymph nodes (or lymph glands) filter the lymph fluid that flows through the lymphatic system. Lymph nodes collect fluid from discrete regions of the body and are often examined for the presence of metastasizing cancer cells.. The lymphatic vessels of the prostate carry lymphatic fluid to a mass of lymph nodes located in the pelvic region. Learn more about the lymphatic system here.

Factors that may influence risk of developing prostate cancer include:

• Age
• Family History of Prostate Cancer
• Race
• Dietary Factors
• Infection with HPV/EBV
• Alcohol Consumption 

The relative effects of these and other risk factors in any given case of cancer is variable and very difficult to determine with accuracy at this time.

Age

Risk of prostate cancer increases dramatically with age. Most patients are diagnosed with the disease over the age of 50.3 For more information about the relationship between age and cancer, refer to the Mutation section.

Family History of Prostate Cancer

It is possible to inherit dysfunctional genes that lead to the development of a familial form of a particular cancer type. Individuals with a family history of prostate cancer are therefore at an increased risk of developing the disease. The degree of risk depends upon the type of relative affected. For example, risk is higher if an immediate family member has been diagnosed with prostate cancer.4 The more closely related an individual is to someone with prostate cancer, the more likely they will share the same genes that predisposed the affected individual. Risk increases with the number of relatives affected.

Studies have linked several prostate cancer susceptibility genes to different locations within the genomeThe full set of genes in an organism. Humans have an estimated 25,000 protein-encoding genes in their genome..5The mechanisms by which these genes lead to cancer, however, are still not well understood.

Race

African American men have the greatest incidence of prostate cancer in the United States. Cancer survival rates are greatly affected by the stage at which a cancer is detected. Compared to both European American and Hispanic men in the United States, African American males are also more likely to be diagnosed at a more advanced stage. Reasons for these differences among ethnic groups are still unclear. Such differences may be due to a combination of genetic, environmental, and/or social factors.6

Dietary Factors

It is very difficult to identify dietary items that cause a particular cancer. Studies indicate that many dietary factors may influence prostate cancer risk. It has been suggested that a diet rich in dairy and meat products may be associated with a higher risk, while a diet rich in fish and tomato-based products may be associated with a lower risk of prostate cancer.7 Studies suggest the accumulation of carcinogens that are generated when red meat is cooked at high temperatures may be a potential prostate cancer risk factor. 8

Infection with Human  Papillomavirus and Epstein-Barr VirusThe smallest type of organism known. A single virus particle (called a virion) is much smaller than a cell. Viruses reproduce by invading cells and forcing the cells to make progeny virions. Viruses generally have specific host cells which they infect. Some virus types are associated with specific cancers and can convert normal cells into cancer cells. Examples of viruses associated with cancer are: papillomavirus-cervical cancer, hepatitis virus-liver cancer, Epstein-Barr virus-Burkitt's lymphoma. Virus-induced transformation of cells was one of the very first model systems for the study of cancer. Viruses have also been a key tool in the identification of many oncogenes. Because of their great ability to enter target cells viruses such as adenoviruses are being examined for their ability to deliver genes to cancer cells.

A 2012 Australian study examining both cancerous and healthy prostate tissue found an association between infection with HPV and EBV and an increased risk of prostate cancer.  The role of the viruses in causing the cancer is not yet known.9

Alcohol Consumption

A 2016 review by BMC cancer links low, medium, high and higher alcohol intake with the occurrence of prostate cancer when compared with cancer development of those who abstain from alcohol consumption. The review incorporated information from over 300 studies to come to this conclusion, which helps validate the legitimacy of their claims.  This information is important because now prostate cancer can be assessed in conjunction with other alcohol-related diseases.10 

Symptoms

There are often no symptoms associated with early-stage prostate cancer. However, most cases of prostate cancer are diagnosed before symptoms develop through screening. The American Cancer Society lists the following symptoms associated with later-staged prostate cancer:11

• Inability to urinate
• Discontinuous or weak urine flow
• Difficulty in starting or stopping urine flow
• Frequent urination, especially at night
• Blood in urine
• Pain or burning with urination
• Continuous back, pelvis, or upper thigh pain

A physician should be consulted if they persist. It is important to note, however, that these symptoms may be caused by factors unrelated to prostate cancer.

Click here for information about prostate cancer treatments and services at the Winship Cancer Institute of Emory University.

Prostate cancer is detected in several ways. The method used depends, in part, on the patient's preference and whether the cancer is causing any symptoms.  Choosing any of the following will take you to the Diagnosis and Detection section.  You can return to learn more about prostate cancer.

Digital Rectal Examinations

Prostate-Specific AntigenAny substance capable of being recognized by the immune system. Recognition of such a substance leads to the generation of an immune response. (PSA) Test

BiopsyA medical procedure in which a sample of tissue is removed for examination. Biopsies can range from a small sample drawn into a needle to samples taken during more invasive surgery.

The Pathology Report
If there is a suspicion that a patient may have prostate cancer, a sample of tissue (biopsy) may be taken for examination. After a biopsy is taken, the physician who performed the biopsy sends the specimen to a pathologist. The pathologist examines the specimens at both the macroscopic (visible with the naked eye) and microscopic (requiring magnification) levels and then sends a pathology report to the physician. The report contains information about the tissue's appearance, cellular makeup, and state of disease or normalcy. For more information about the pathology report, refer to the Diagnosis & Detection section.

Staging
Staging a cancer is a way of describing the extent of the disease. A common method of staging is called the T/N/M system, which assigns a degree of severity based on the size, location, and spread of cancer in the body. The most widely used grading system for prostate cancer, however, is the Gleason Grading System. This system assigns a number based on the aggressiveness of the prostate cancer. Details of the T/N/M system and Gleason Grading System can be found in the Diagnosis & Detection section.

Genetic changes that occur in cancer include mutation of key regulatory genes, changes in proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins. products, and changes in the amount of product produced by genes (gene expressionThe act of transcription and, if needed, translation of a gene. Regulation of gene expression is tightly regulated. Genes must only be expressed in the correct cells, at the right time and in the correct amount. Abnormal gene expression is always found in cancer cells.). As changes accumulate, cells become more abnormal and cancer progresses. Details about these changes can be found in the Mutation section. Some of the genes that have been shown to be important in the development of prostate cancer are listed below and discussed on the following pages:

• Androgen Receptors
• PTEN Gene
• TP53 Gene

The Androgen Receptor

Male hormones such as testosteroneTestosterone is the main male sex hormone and is responsible for the generation of the secondary sex characteristics. The hormone is produced in male testes and is normally found to a much lesser extent in females. are known as androgens. Androgen receptors (AR) are proteins found within the cell that help control growth and division. Once an androgen enters the cell and binds to an AR, the complex acts as a transcription factorA molecule, usually a protein, that binds to DNA at the start of a gene, enabling that gene to be transcribed (copied) to form an RNA molecule. Transcription factors bind to specific parts of genes called promoters, so called because they promote transcription. Transcription factor binding to gene promoters is critical for regulation of the process. Since transcription factors ultimately control what genes are turned 'on' at any given time, they are essential for the proper functioning of the cell. A wide range of transcription factors are known to be associated with cancer. Changes, or mutations, in these genes leads to a deregulation of the whole process. Some key transcription factors are the p53 and Rb proteins. , promoting cell growth. These receptors are important regulators of normal cell growth in the prostate.12

Several mutations can cause overexpressionA term describing the abnormal regulation of a gene. When the controls on gene expression (transcription) break down, the gene may be turned off inappropriately, or it may be transcribed at high rates. High transcription levels lead to the production of large amounts of mRNA and large amounts of the protein product. If that protein is important in regulating cell division or some other key process, then too much protein can lead to unregulated cell division. An example is the overexpression of the Her2/neu protein on the surface of some breast and ovarian cancers. The presence of large amounts of this protein increases abnormal cell division. of the AR gene, resulting in unregulated prostate cell growth:

• The AR gene may be amplified. The resulting increase in expression of AR can lead to cell growth even in the presence of low levels of androgen.
  • Learn about gene amplificationAlso: gene amplification. An abnormal process in which many copies of the same chromosome region are produced via DNA replication. The result can be a small 'microsatellite' chromosome or a region of DNA within a chromosome with many contiguous copies of a small set of genes.
• Mutations in the AR gene can alter the resulting protein and result in loss of binding specificity. Such mutations may result in the activation of the receptor by substances other than androgen.
• Mutations may cause the androgen receptor to be activated without the binding of any molecules.13

The correlation between AR expression and prostate cancer has led to the development of anti-androgens as a treatment option. For more information about the use of anti-androgen molecules in therapy, refer to the Cancer Treatments section.

Prostate cancers can develop the ability to grow without stimulation by an androgen. These cancers are called androgen-independent, or androgen-negative prostate cancers. Androgen-independent cancers are unlikely to respond to anti-androgen therapy.

PTEN

PTEN (phosphatase and tensin) homolog deleted on chromosomeA long DNA molecule containing genetic information (genes). Humans have 46 chromosomes. One set of 23 is inherited from each parent. A full set of chromosomes is present in the nucleus of each human cell. 10 is a tumor suppressorA gene that functions in the control of cell division. Tumor suppressors normally work to limit cell division and may be contrasted with oncogenes. gene often mutated in prostate cancer. This gene plays an important role in several cellular pathways, including the control of prostate basal cell growth. Mouse models suggest that proliferationRefers to cell division. The proliferation rate is an indicator of how quickly a tumor is growing. The proliferation rate may be represented as a percentage, showing what fraction of the cells are actively involved in the division process. of these cells is an important step in the initiation and early progression of prostate cancer.14

For more information about tumor suppressors, refer to the Cancer Genes section.

p53A tumor suppressor gene that is mutated in over 50% of cancers of all types. The p53 protein is a transcription factor that controls entry into the cell division cycle. Many signals about the health of a cell are relayed to the p53 protein. This results in a decision by the cell as to whether or not cell division should occur. If the cell is damaged and can not be repaired, the p53 protein is involved in triggering a chain of events that causes the cell to kill itself in a process termed apoptosis. Cells defective for p53 do not have these controls and tend to divide even when conditions are not favorable. Like all tumor suppressors, the p53 gene is normally involved in slowing or monitoring cell division.

p53 is a tumor suppressor gene involved in DNAAbbreviation for deoxyribonucleic acid. Composed of very long strings of nucleotides, which are abbreviated as A, C, G and T. DNA is the storage form of our genetic material. All of the instructions for the production of proteins are encoded in our DNA. repair and the regulation of apoptosisAlso called programmed cell death. Apoptosis is a natural process that occurs throughout the lives of almost all animals and plants. The death of the cells is a carefully controlled process that does not generate any inflammation.. p53 mutations occur only in a small fraction of prostate cancers, and are usually associated with metastaticThe term for a cancer that has spread beyond its point of origin. Metastatic disease is responsible for the majority of cancer deaths. tumors.13

• Learn more about abnormal p53 and cancer development

The treatment of prostate cancer can be broken down into two categories: early stage and advanced stage. Early stage treatment involves tumors that are confined to the prostate. Advanced stage treatment involves tumors that have spread beyond the prostate gland. Treatment options are dependent upon size of tumor, location, physical condition of patient, and stage of cancer.

As our focus is on the biology of the cancers and their treatments, we do not give detailed treatment guidelines. Instead, we link to organizations in the U.S. that generate the treatment guidelines.

The National Comprehensive Cancer Network (NCCN) lists the following treatments for prostate cancer:

• Watchful waiting
• Radical prostatectomy
• Transurethral resection of the prostate (TURP)
• External beam radiationIn cancer biology: A cancer treatment in which high energy beams are used to kill cancer cells. Radiation can also cause genetic damage that can lead to cancer. As an example, skin cancer is believed to be greatly increased by exposure to ultraviolet (UV) radiation from the sun.
• Internal radiation: brachytherapy
• HormoneA chemical produced by cells that alters the activity of other cells. The chemicals may be lipids, such as testosterone and estrogen or proteins like insulin. Hormones may act at locations far from their site of origin. Estrogen, for example, is produced primarily by cells in the ovaries but acts on cells in the breast and elsewhere. therapy
• Removal of the testicles (orchiectomy)
• Antiandrogens
• ChemotherapyTreatment of cancer patients with anticancer drugs. Commonly called 'chemo'. These drugs work by attacking cell growth or division. Often these agents are used in combination to take advantage of their different modes of attack on cell division.

Learn more about the treatment for prostate cancer at the Winship Cancer Institute of Emory University.

Learn more about cancer treatments.

Information about clinical trials:

• General clinical trial information from CancerQuest
• Click here for information about clinical trials at the Winship Cancer Institute of Emory University
• Click here for information about clinical trials from the National Cancer Institute.
• Click here for information about clinical trials from Georgia Clinical Trials Online.

Introduction

• Prostate cancer ranks as the second leading cause of cancer death in men.
• Almost all prostate cancers develop in the glandular cells.

Risk Factors

• Risk of prostate cancer increases dramatically with age. Most cases occur after the age of 50.
• The risk is higher if an immediate family member has been diagnosed with prostate cancer.
• In the US, African American men have the greatest incidence of prostate cancer.
• Dietary factors influence the risk of prostate cancer. Meat and dairy may heighten the risk whereas fish and tomato-based foods may lower the risk for prostate cancer.

Symptoms

• Advanced-stage prostate cancer patients experience a wide range of symptoms that may involve urine discoloration, pain with urination, weak urine flow, and others.

Detection and Diagnosis

• A prostate-specific antigen (PSA) test can be used to help detect prostate cancer, but it does not provide a definitive diagnosis.

Pathology Report and Staging

• A pathologist examines a tissue sample micro- and macroscopically in order to create a pathology report.
• Prostate cancer used the Gleason Grading System which assigns a number to the cancer based on its aggressiveness.

Prostate Cancer Tumor Biology

• Many genetic changes occur in cancer. Details can be found in the Mutation section.
• PTEN and TP53 are two of the genes involved in the development of prostate cancer.
• The androgen receptor protein binds androgens in the cell. This complex promotes cell growth and division. The presence or absence of this protein helps determine treatment options for the cancer.

Treatment

• A wide range of treatments exists for prostate cancer including chemotherapy, surgery, hormonal therapies and radiation.
• Foregoing treatment and carefully monitoring the prostate is an option in some cases.

Learn more about prostate cancer or make an appointment at the Winship Cancer Institute of Emory University.