Prostate cancer

Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
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W8MD medical weight loss NYC and sleep center NYC

Prostate cancer is a disease characterized by the development of cancerous cells in the prostate gland, which is part of the male reproductive system. When cells in the prostate mutate and begin to multiply uncontrollably, cancer can occur. These cancer cells have the potential to spread (metastasize) from the prostate to other parts of the body, most commonly the bones and lymph nodes. Prostate cancer can lead to various symptoms, including pain, difficulty in urination, erectile dysfunction, and other related symptoms.

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Prostate cancer (1)

Sagittal anatomy of the male pelvis highlighting the prostate, extracted from Understanding treatment choices for prostate cancer (2000)

Rates of prostate cancer vary significantly worldwide. It is less common in South and East Asia, more common in Europe (with significant variation between countries), and most common in the United States. According to the American Cancer Society, prostate cancer is less common among Asian men, most common among black men, and figures for European men fall in between. However, the reported high rates may be influenced by increased detection rates.

Prostate cancer predominantly affects men over the age of fifty. It is the second most common cancer among men in the United States, causing more male deaths than any cancer except lung cancer. However, many men who develop prostate cancer never experience symptoms, receive no treatment, and eventually die from other causes. Various factors, such as genetics and diet, have been implicated in the development of prostate cancer. As of 2006, prostate cancer is not considered preventable.

The detection of prostate cancer often occurs through physical examination or screening tests such as the prostate-specific antigen (PSA) test. However, there is ongoing concern regarding the accuracy and usefulness of the PSA test. Suspected prostate cancer is typically confirmed through a biopsy, in which a sample of prostate tissue is examined under a microscope. Additional tests, including X-rays and bone scans, may be conducted to assess the extent of cancer spread.

Prostate cancer can be treated through surgery, radiation therapy, hormone therapy, chemotherapy, or a combination of these approaches. Factors such as the patient's age, overall health, stage of cancer, and response to initial treatment play a significant role in determining the outcome of the disease. Since prostate cancer is primarily seen in older men, many may die from other causes before the cancer spreads or causes symptoms. This makes treatment decisions challenging, as the potential benefits and harms must be carefully evaluated in terms of patient survival and quality of life.

The Prostate

The prostate is an organ exclusively found in the male reproductive system. It contributes to the production and storage of seminal fluid. In adult men, a typical prostate is about three centimeters long and weighs approximately twenty grams. It is situated in the pelvis, beneath the urinary bladder and in front of the rectum. The prostate surrounds a portion of the urethra, the tube responsible for transporting urine from the bladder during urination and semen during ejaculation. Given its location, prostate diseases often affect urination, ejaculation, and defecation. The prostate consists of numerous small glands that contribute to approximately twenty percent of the fluid in semen. In prostate cancer, the cells of these prostate glands undergo mutations, leading to the development of cancer cells. The proper functioning of the prostate glands relies on male hormones, particularly androgens, which include testosterone (produced in the testes), dehydroepiandrosterone (produced in the adrenal glands), and dihydrotestosterone (produced in the prostate itself). Androgens are also responsible for secondary sex characteristics, such as facial hair growth and increased muscle mass.

Symptoms

Early-stage prostate cancer usually does not present noticeable symptoms. It is often detected during routine checkups when a screening test reveals an elevated prostate-specific antigen (PSA) level. However, prostate cancer can cause symptoms similar to those of other conditions such as benign prostatic hypertrophy. These symptoms may include frequent urination, increased urination at night (nocturia), difficulty initiating and maintaining a steady urine stream, blood in the urine (hematuria), and painful urination. Prostate cancer can also affect sexual function, leading to difficulties in achieving an erection or experiencing painful ejaculation.

As prostate cancer advances and spreads to other parts of the body, additional symptoms may arise. The most common symptom is bone pain, often in the spine, pelvis, or ribs, resulting from cancer metastasis to these areas. Prostate cancer that spreads to the spine can also exert pressure on the spinal cord, causing weakness in the legs, urinary incontinence, and fecal incontinence.

Pathophysiology

Prostate cancer is classified as an adenocarcinoma, a type of glandular cancer that originates from the cells of the prostate gland. The peripheral zone of the prostate gland is the region where adenocarcinoma is most commonly found. Initially, cancer cells form small clusters within otherwise normal prostate glands, a condition known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN). Although PIN is not considered a cancer precursor, it is closely associated with cancer development. Over time, these cancer cells begin to multiply and spread into the surrounding prostate tissue, forming a tumor. As the tumor grows, it may invade neighboring organs such as the seminal vesicles or rectum. Additionally, cancer cells may gain the ability to enter the bloodstream and lymphatic system, facilitating metastasis. Prostate cancer is categorized as a malignant tumor because it consists of cells that can invade and spread to other parts of the body. The most common sites of metastasis for prostate cancer are the bones, lymph nodes, rectum, and bladder.

Epidemiology

The specific causes of prostate cancer are not yet fully understood. However, several factors contribute to an individual's risk of developing the disease, including age, genetics, race, diet, lifestyle, medications, and other factors. Age is a primary risk factor, as prostate cancer is uncommon in men under the age of 45 but becomes more prevalent with advancing age. The average age at the time of diagnosis is 70. However, many men with prostate cancer remain unaware of their condition, as most cases do not progress to the point of causing symptoms, and individuals often die from unrelated causes before prostate cancer becomes clinically significant. Autopsy studies have revealed prostate cancer in approximately 30% of men in their 50s and 80% of men in their 70s. In the United States, an estimated 230,000 new cases of prostate cancer and 30,000 deaths from the disease were reported in 2005.

Genetic factors contribute to an individual's risk of developing prostate cancer. The incidence of prostate cancer varies among different racial groups, with black men being more commonly affected than white or Hispanic men. Prostate cancer also tends to be more aggressive and have a higher mortality rate in black men. A family history of prostate cancer, particularly having a brother or father with the disease, doubles the risk of developing prostate cancer. Studies conducted on twins suggest that approximately 40% of prostate cancer risk can be attributed to inherited factors. However, no single gene has been identified as solely responsible for prostate cancer, and multiple genes are believed to play a role. The BRCA1 and BRCA2 genes, which are associated with ovarian and breast cancer in women, have also been implicated in prostate cancer.

Dietary factors and nutritional intake can influence prostate cancer risk. Some studies suggest that higher levels of the short-chain omega-3 fatty acid alpha-linolenic acid are associated with an increased risk of prostate cancer. However, elevated levels of long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with a decreased incidence of prostate cancer. Research has also indicated that elevated blood levels of trans fatty acids, particularly those resulting from the hydrogenation of vegetable oils, are linked to an increased risk of prostate cancer. Other dietary factors that may contribute to an increased risk include low intake of vitamin E (found in green, leafy vegetables), lycopene (found in tomatoes), omega-3 fatty acids (found in fatty fish like salmon), and the mineral selenium. Lower blood levels of vitamin D have also been associated with an increased risk of prostate cancer, potentially due to decreased exposure to ultraviolet (UV) light, which helps the body produce vitamin D.

There are several links between prostate cancer and certain medications, medical procedures, and medical conditions. Daily use of anti-inflammatory medications such as aspirin, ibuprofen, or naproxen sodium may decrease the risk of prostate cancer. Cholesterol-lowering drugs known as statins have also been associated with a reduced risk. However, sterilization through vasectomy may increase the risk of prostate cancer, although there are conflicting data on this association. Additionally, more frequent ejaculation has been linked to a decreased risk of prostate cancer. One study found that men who ejaculated five times a week in their 20s had a lower rate of prostate cancer. Infection or inflammation of the prostate (prostatitis) may also increase the likelihood of developing prostate cancer, particularly infections caused by sexually transmitted infections such as chlamydia, gonorrhea, and syphilis. Elevated blood levels of testosterone, a male hormone, have also been associated with an increased risk of prostate cancer.

Screening

Screening for prostate cancer aims to detect unsuspected cancers at an early stage. Screening tests may lead to further diagnostic procedures, such as a biopsy, in which small samples of the prostate are removed for closer examination. As of 2006, prostate cancer screening options primarily include the digital rectal examination (DRE) and the prostate-specific antigen (PSA) blood test. However, prostate cancer screening remains a topic of debate due to uncertainties regarding the balance between the benefits of early detection and the risks associated with follow-up tests and cancer treatments.

Prostate cancer is a slow-growing cancer that is highly prevalent in older men. Many prostate cancers never progress to a life-threatening stage, and most men with prostate cancer die from unrelated causes before the cancer impacts their lives. PSA screening may detect small cancers that would never become clinically significant, leading to overdiagnosis and subsequent unnecessary testing and treatment. Follow-up tests, such as prostate biopsy, can cause discomfort, bleeding, and infection. Additionally, prostate cancer treatments can result in urinary incontinence and erectile dysfunction. Therefore, careful consideration of the risks and benefits of diagnostic procedures and treatment is essential before conducting PSA screening.

Prostate cancer screening typically begins after the age of fifty, but earlier screening may be offered to black men or those with a strong family history of prostate cancer. While no official cutoff age has been established, healthcare providers often discontinue PSA monitoring in men older than 75 years due to concerns that the potential harms of prostate cancer therapy outweigh the benefits as age advances and life expectancy decreases.

Digital Rectal Examination

The digital rectal examination (DRE) is a procedure in which a healthcare provider inserts a lubricated, gloved finger into the rectum to assess the size, shape, and texture of the prostate gland. Areas that feel irregular, hard, or lumpy may require further evaluation, as they could potentially indicate the presence of cancer. However, the DRE only evaluates the back portion of the prostate, even though 85% of prostate cancers originate in that region. The use of DRE as the sole screening test has not been shown to prevent prostate cancer deaths.

Prostate-Specific Antigen

The PSA test measures the level of prostate-specific antigen, an enzyme produced by the prostate gland. PSA is a serine protease, similar to kallikrein, and its primary function is to liquefy semen after ejaculation, aiding the movement of sperm through the cervix.

Typically, PSA levels under 4 ng/mL (nanograms per milliliter) are considered normal, while levels above 4 ng/mL are considered abnormal. However, in men over 65 years old, levels up to 6.5 ng/mL may be acceptable based on laboratory reference ranges. PSA levels between 4 and 10 ng/mL indicate a higher-than-normal risk of prostate cancer, but the risk does not necessarily increase within this range. When the PSA level exceeds 10 ng/mL, the association with cancer becomes stronger. Nevertheless, the PSA test is not perfect, as some men with prostate cancer may have normal PSA levels, while many men with elevated PSA levels do not have prostate cancer.

PSA levels can be affected by factors other than cancer. Conditions such as benign prostatic hypertrophy (BPH), which is an enlargement of the prostate, and prostatitis, an inflammation of the prostate, can cause elevated PSA levels. Certain medications used to treat BPH or baldness, such as finasteride and dutasteride, can lower PSA levels by 50% or more. Therefore, interpreting PSA results requires careful consideration of various factors.

To improve the effectiveness of PSA screening, several approaches have been developed. Age-specific reference ranges that consider the natural increase in PSA levels with age have been implemented to enhance sensitivity and specificity. The rate of PSA rise over time, known as PSA velocity, has been evaluated in men with PSA levels between 4 and 10 ng/mL. However, as of 2006, PSA velocity has not proven to be an effective screening test. Comparing the PSA level with the size of the prostate, assessed through ultrasound or magnetic resonance imaging, has also been studied. This comparison, called PSA density, is costly and, as of 2006, has not demonstrated sufficient effectiveness as a screening test. PSA can exist in the blood either as free PSA or bound to other proteins. Measuring the ratio of free to total PSA may provide additional information for screening, but its widespread use is limited as of 2006 due to questions about its utility.

Confirming the Diagnosis

When a man presents with symptoms suggestive of prostate cancer or when screening tests indicate an increased risk, further diagnostic evaluations are offered. The only definitive method to confirm a prostate cancer diagnosis is through a biopsy, which involves removing small tissue samples from the prostate for microscopic examination. However, before proceeding with a biopsy, additional tools may be used to gather more information about the prostate and urinary tract. Cystoscopy allows visualization of the urinary tract from inside the bladder using a thin, flexible camera tube inserted through the urethra. Transrectal ultrasonography uses sound waves from a probe inserted into the rectum to create an image of the prostate.

If cancer is suspected, a biopsy is recommended. During a biopsy, a urologist obtains tissue samples from the prostate using a biopsy gun that quickly inserts and removes special hollow-core needles. Typically, three to six samples are taken from different areas of the prostate. These tissue samples are then examined under a microscope to determine the presence of cancer cells and evaluate their microscopic features, known as the Gleason score, which helps assess the aggressiveness of the cancer. Prostate biopsies are usually performed on an outpatient basis and rarely require hospitalization. Approximately 55% of men report discomfort during a prostate biopsy.

Staging

Determining the stage of prostate cancer is crucial for evaluating the extent of the disease and guiding treatment decisions. The most commonly used staging system is the TNM system (Tumor/Nodes/Metastases), which incorporates the size of the tumor, the involvement of lymph nodes, and the presence of metastases.

One of the key distinctions made by staging systems is whether the cancer is still confined to the prostate or if it has spread beyond it. In the TNM system, clinical T1 and T2 cancers are localized within the prostate, while T3 and T4 cancers have advanced and spread to other areas. Various tests can be utilized to assess the presence of metastasis. Computed tomography (CT) scans can evaluate the spread of cancer within the pelvis, while bone scans can detect metastasis to the bones. Endorectal coil magnetic resonance imaging (MRI) can provide detailed images of the prostate capsule and seminal vesicles for closer evaluation.

Treatment

Prostate cancer can be treated through different approaches, depending on the stage of the disease, the age and overall health of the patient, and individual considerations. Common treatment modalities include surgery, radiation therapy, hormone therapy, chemotherapy, and sometimes a combination of these methods.

Surgery, such as radical prostatectomy, involves the removal of the entire prostate gland and surrounding tissues. This procedure can be performed through open surgery or minimally invasive techniques, such as laparoscopic or robotic-assisted surgery. Radiation therapy uses high-energy beams to target and destroy cancer cells. It can be delivered externally through external beam radiation therapy (EBRT) or internally through brachytherapy, which involves placing radioactive seeds directly into the prostate. Hormone therapy, also known as androgen deprivation therapy (ADT), aims to suppress the production or action of male hormones that fuel the growth of prostate cancer cells. Chemotherapy, which uses drugs to kill cancer cells, is typically reserved for advanced cases or when other treatments have been ineffective.

The selection of treatment depends on various factors, including the stage and aggressiveness of the cancer, the patient's age and overall health, and the potential side effects and risks associated with each treatment option. For older men with localized prostate cancer, active surveillance may be an appropriate approach. This involves regular monitoring of the cancer's progression through PSA tests, biopsies, and imaging, with the goal of initiating treatment if the cancer shows signs of progression. The decision regarding treatment is often a shared decision-making process between the patient and the healthcare team, considering the potential benefits, risks, and impact on the patient's quality of life.

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List of Urology doctors (US)

Comprehensive list of Urologists in the United States.

See also

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External links

• Prostate Cancer Centre - The UK's leading Prostate Cancer Centre offering all the latest therapies in the treatment of prostate cancer including brachytherapy, cryotherapy and laparoscopic radical prostatectomy and HIFUI
• Prostate Cancer Foundation
• American Cancer Society
• ASTRO information and pictures on how radiation therapy works to treat prostate cancer
• Malecare Prostate Cancer Support Groups and Multi-Lingual website, nonprofit
• National Institute on Aging Information Center
• National Kidney and Urologic Diseases Information Clearinghouse
• Prostate Cancer Survivor One survivor's story
• Many NCI publications may be viewed or ordered on the Internet at http://cancer.gov/publications
• Zero - The Project to End Prostate Cancer
• The Prostate Cancer Charity (UK)

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