Overview of Prostate Cancer
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor, updated 1/2021
The prostate is a walnut sized gland is part of the male reproductive system. It makes most of the semen that carries sperm and is located beneath the bladder and surrounds the upper part of the urethra, the tube that carries urine from the bladder. The prostate is divided into three zones enclosed by a capsule. The prostate capsule separates the prostate from the rest of the body.
Prostate cancer is uncommon before age 50, and experts believe that most elderly men have traces of it.
About 238,500 men are diagnosed with prostate cancer in the US each year and African-American men are more likely to get the disease have the highest death rate. Prostate cancer in its early stages can be treated. Cancer that has spread beyond the prostate (such as to the bones, lymph nodes, and lungs) may not be curable with current therapies, but can be effectively controlled for many years.
The prostate gland typically enlarges as men grow older. This growth of the gland is called benign prostatic hyperplasia (BPH) and most often occurs in the transition zone of the prostate, which surrounds the urethra. Prostate growth in this area may block the bladder or urethra and prevent the flow of urine. Men may experience frequent or painful urination; blood in the urine or semen; and stiffness or pain in the lower back. These symptoms may be caused by BPH or they may be signs of cancer.
Prostate cancer occurs when the cells in the prostate gland grow out of control. When cells grow out of control, they initially spread within the prostate and then grow through the capsule that covers the prostate into neighboring organs, or break away and spread through the bloodstream and lymphatic system to other parts of the body. Prostate cancer can be relatively harmless or extremely aggressive. Some prostate cancers are slow growing, causing few clinical symptoms. In these cases, a patient will often die with prostate cancer rather than from prostate cancer. Aggressive cancers spread rapidly to the lymph nodes, other organs and especially, bone.
The suspicion of prostate cancer usually arises from an elevated prostate-specific antigen (PSA) blood level test and/or a digital rectal exam (DRE). PSA is a protein that is normally secreted and disposed of by the prostate gland. High PSA levels sometimes indicate the presence of cancer; however, more tests are needed to confirm this suspicion. During a DRE, a physician inserts a gloved finger into the rectum to assess the texture and size of the prostate.
If the results from a PSA blood test and/or a DRE suggest that prostate cancer may be present, this suspicion needs to be confirmed by a biopsy. Prostate cancer is diagnosed by performing one or more biopsies of the prostate gland. The biopsy will determine whether a patient has BPH, cancer or another medical problem. During a biopsy, a needle is used to remove several small pieces of prostate tissue through the rectum. These tissue samples are then examined under the microscope to determine whether cancer cells are present.
Risk factors for Prostate Cancer
Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get prostate cancer and not having risk factors doesn’t mean that you will not get cancer, it simply means that you are at greater risk than normal to develop the cancer.
- Advanced age is the biggest—but not the only—risk factor for prostate cancer. Race- Scientists don’t yet know why, but men of African descent are 79% more likely to develop prostate cancer compared with white men, and 2.2 times more likely to die from the disease.
- Diet - A high fat, high processed carbohydrate diet is associated with increased risk of prostate cancer. Likewise, lack of vegetables in the diet (especially broccoli-family vegetables) is linked to a higher risk of aggressive prostate cancer, but not to low-risk prostate cancer.
- Obesity - Men who are overweight or obese are at greater risk of ultimately developing an aggressive form of prostate cancer. Research has shown that in obese men, recovery from surgery tends to be longer and more difficult, and the risk of dying from prostate cancer can be higher.
- Smoking - smoking has not been thought to be a risk factor for low-risk prostate cancer, it may be a risk factor for aggressive prostate cancer.
- Family history - Genes for disease can run in families. Men who have a relative with prostate cancer are twice as likely and those with 2 or more relatives are nearly 4 times as likely to develop prostate cancer. The risk is even higher if the affected family members were diagnosed before age 65.
- Genetic factors - Because family members share many genes there may be multiple genetic factors that contribute to the risk of developing prostate cancer. There are also some individual genes that we have learned increase the risk of prostate cancer, and men with these genes may need to be screened differently or consider changes in treatment.
Prostate Cancer Genetics
Each patient with prostate cancer develops their own particular form of prostate cancer that can be identified based on the cancer-causing genetic mutations in a patient’s tumor. A genetic mutation is a change in part of the normal DNA that makes up a gene. The cancer causing mutations can be germline (inherited) or somatic (acquired) and its identification can be used to treat that cancer with a specific precision cancer medicine. In 12%-20% of families certain cancer-causing germline mutations are passed down from mothers and fathers to sons and daughters.
Some of the genes that are responsible for prostate cancer are also responsible for cancers in daughters, and vice versa; for example, if your mom has the BRCA gene for breast cancer, this increases your risk for prostate cancer. It can be important for men to be screened early if you have a history of cancer in your family, even if it’s not prostate cancer. Screening can be done with a simple saliva test or blood test that looks for about 60 genes across all cancers that are considered to be inheritable, and about 20 specific genes in prostate cancer families. Knowing your germline DNA helps you understand the risk that you and your children face, so that you can create a precision family health plan for prevention and earlier detection.
Newly Diagnosed With Prostate Cancer
A new diagnosis of cancer can be a shock, making you feel out of control and overwhelmed. Getting informed can help alleviate these feelings. Remember, very few cancers require emergency treatment; you have time to learn about your diagnosis and treatment options, ask questions, and get a second opinion. This section is designed to help you address your initial questions before you move forward with your treatment.
How is prostate cancer diagnosed?
Prostate cancer once detected must be confirmed with a biopsy and carefully evaluated with a number of other tests in order to determine an accurate diagnosis, stage, and learn additional useful information that can direct treatment. If laboratory tests or physical examination results suggest that prostate cancer may be present, you will need to have a prostate biopsy. A biopsy is the only way to know for sure whether an individual has cancer. During a biopsy, a needle is used to remove several small pieces of prostate tissue through the rectum. These pieces of prostate tissue are examined under the microscope to determine whether cancer cells are present. If cancer cells are present, an assessment of how aggressive or abnormal the cancer appears is performed.
Tests for Prostate Cancer
Prostate Specific Antigen (PSA) blood test
The PSA blood test is used mainly to screen for prostate cancer in men without symptoms.
- Most men without prostate cancer have PSA levels under 4 nanograms per milliliter (ng/mL) of blood. The chance of having prostate cancer goes up as the PSA level goes up.
- When prostate cancer develops, the PSA level usually goes above 4. Still, a level below 4 does not guarantee that a man doesn’t have cancer. About 15% of men with a PSA below 4 will have prostate cancer on a biopsy.
- Men with a PSA level between 4 and 10 have about a 1 in 4 chance of having prostate cancer. If the PSA is more than 10, the chance of having prostate cancer is over 50%.
Transrectal ultrasound (TRUS)
A TRUS is used to look at the prostate when a man has a high PSA level, an abnormal rectal exam or during a prostate biopsy to guide the needles into the correct area of the prostate.
During a TRUS a small probe the width of a finger is lubricated and placed in the rectum. The probe gives off sound waves that enter the prostate and create echoes. When the probe detects the echoes a computer turns them into a black and white image of the prostate.
A TRUS typically takes no longer than 10 to 15 minutes and is done in a doctor’s office or outpatient clinic. You will feel some pressure when the probe is inserted, but it is usually not painful. The area may be numbed before the procedure.
TRUS can also be used to measure the size of the prostate gland, which can help determine the PSA density and as a guide during some brachytherapy or cryotherapy treatment.
If certain symptoms, an abnormal DRE or a high PSA suggest you might have prostate cancer a biopsy is required to confirm a diagnosis.
A core needle biopsy is the main method used to diagnose prostate cancer and is is usually performed by a urologist that uses TRUS to “see” the prostate gland. Most doctors numb the area first by injecting a local anesthetic alongside the prostate. The doctor inserts a thin, hollow needle through the wall of the rectum and into the prostate. Each biopsy usually causes only a brief uncomfortable sensation because it is done with a special spring-loaded biopsy instrument. The device inserts and removes the needle in a fraction of a second. Most urologists will take about 12 core samples from different parts of the prostate.
The biopsy samples will be sent to a lab, where they will be looked at a microscope to see if they contain cancer cells. It usually takes at least 1 to 3 days for results to become available, but it can sometimes take longer.
MRI Fusion Guided Prostate Biopsy
A fusion guided prostate biopsy combines magnetic resonance imaging (MRI) with ultrasound to more effectively target abnormal prostate tissue for biopsy. An MRI scan is better than ultrasound at revealing details in soft tissue, such as the prostate gland but doctors cant perform a biopsy procedure from within the MRI chamber. Combining MRI and ultrasound however “fuses” detailed MRI scans taken before the biopsy procedure with live, real-time ultrasound images of the prostate.
Patients first undergo a MRI of the prostate, to identify any suspicious areas. Patients then have an ultrasound-guided prostate biopsy. During the biopsy, the images from the MRI are fused in real-time with images from the ultrasound-guided prostate biopsy. This simultaneous combination of images guides the physician with greater accuracy during the biopsy to visualize and evaluate questionable areas. The combined images enable physicians to better differentiate suspicious cells from healthy prostate tissue, and attain a clearer view of the biopsy needle.
A fusion guided biopsy can more accurately identify suspicious areas within the prostate, reduce the amount of tissue samples required, and is less painful with a lower risk of infection and bleeding. A fusion guided biopsy is typically recommended when there is an elevated prostate-specific antigen (PSA) levels greater than four or a prior negative TRUS guided biopsy with a continued elevated or rising PSA.
Next Generation Sequencing (NGS)
All prostate cancer patients should consider having NGS performed on a biopsy positive for prostate cancer and from their blood. Cancer cells may differ from one another based on what genes have mutations. Precision cancer medicine requires molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome to identify specific genetic abnormalities that can be targeted for treatment.
The next-generation sequencing process involves fragmenting cancer DNA/RNA into multiple pieces, adding adapters, sequencing the libraries, and reassembling them to form a genomic sequence that defines a specific cancer causing mutation.
Once a genetic abnormality is identified, a specific targeted therapy that attacks a specific mutation or other prostate cancer-related change in the DNA programming of the cancer cells can be selected for treatment. This “genomic testing” is performed on a biopsy sample of the cancer and increasingly in the blood using a “liquid biopsy.” Patients should make sure NGS testing is performed on both their tissue and blood at the time of diagnosis if possible.
What is a cancer stage?
If a prostate cancer diagnosis is confirmed by biopsy, the next step is to determine the stage or extent of spread of the cancer. Stage describes how far the cancer has spread. Determining the stage of the cancer may require a number of procedures, including additional surgery (lymph node evaluation), blood tests, ultrasound, chest x-rays and occasionally, CT/MRI or bone scans. There are many staging systems, but TNM is the most common. “T” refers to the size of the tumor, “N” to the number of lymph nodes involved, and “M” to metastasis. TNM staging measures the extent of the disease by evaluating these three aspects and assigning a stage, which is usually between 0-4. Generally, the lower the stage, the better the treatment prognosis (outcome).
Stage I: The cancer is confined to the prostate and involves a limited amount of the prostate. Gleason score and PSA are relatively low.
Stage II: The cancer is more advanced than Stage I, but is still confined within the prostate.
Stage III: The cancer extends through the capsule of tissue that surrounds the prostate and may involve the seminal vesicles (nearby glands that help produce semen).
Stage IV: The cancer involves lymph nodes and/or organs or structures outside the prostate other than the seminal vesicles.
Recurrent/Relapsed: The prostate cancer has been detected or has returned (recurred/relapsed) following an initial treatment with surgery, radiation, hormonal therapy, or chemotherapy.
Imaging Tests to Look for Prostate Cancer
Bone scan: If prostate cancer spreads to distant sites, it often goes to the bones first. During a bone scan a small amount of low-level radioactive material is injected into a vein and it settles in damaged areas of bone throughout the body. A special camera detects the radioactivity and creates a picture of the skeleton showing the abnormal areas.
A bone scan may suggest cancer in the bone, but to make an accurate diagnosis x-rays, CT or MRI scans, or even a bone biopsy might be needed.
Computed tomography (CT) scan: CT scans use x-rays to make detailed, cross-sectional images of your body. CT scans are not as useful as magnetic resonance imaging (MRI) for looking at the prostate gland itself.
Magnetic resonance imaging (MRI): MRI scans show detailed images of soft tissues in the body. MRI scans use radio waves and strong magnets instead of x-rays. A contrast material called gadolinium is often injected into a vein before the scan to better see details.
MRI scans can give a very clear picture of the prostate and show if the cancer has spread outside the prostate into the seminal vesicles or other nearby structures.
To improve the accuracy of the MRI, you might have a probe, called an endorectal coil, placed inside your rectum for the scan. This can be uncomfortable. If needed, medicine to make you feel sleepy (sedation) can be given before the scan.
How does diagnosis determine treatment?
Overall treatment is determined based on the stage of the cancer and other prognostic factors like Gleason score and the genomic profile can influence treatment decisions. Higher stage cancers typically receive more aggressive treatments and lower stage disease less aggressive treatment.
Research has indicated that identifying the stage of disease may not be the most accurate technique for determining the cancers aggressiveness. For example, some early stage diseases may recur or progress even after treatment, while some late stage cancers may stay in remission. These findings suggest that there may be factors other than how the cancer looks under a microscope and how far it has spread at the time of diagnosis that may better indicate the likelihood that a given cancer will recur and/or progress.
Human genomics, which is the study of the entire genetic material of humans, has provided invaluable tools for identifying the genetic components of cancers. The mapping of the human genome, which consists of 30,000 to 70,000 genes, has laid the ground work for understanding the role those genes play. Cancer is many different diseases; however, one aspect of all cancers that is similar is damage to the DNA resulting in uncontrolled cell growth. Identifying the genes for each cancer type that are involved in the capacity grow and spread may provide valuable prognostic information.
How is prognosis determined?
The probable course and/or outcome of the cancer is called the prognosis. Identifying factors that indicate a better or worse prognosis will help you and your doctor plan your treatment. There are many factors that help determine your prognosis. Age, other health conditions and cancer stage effect your prognosis and influence treatment options. The Gleason score and prostate specific antigen blood (PSA) blood level provide additional information that will help individuals make treatment decisions especially for early stage cancers.
Gleason Score: Cancer that is removed by surgical resection or needle biopsy will be classified according to the Gleason Grading System for prostate cancer. This grading system, on a scale of 6-10, helps physicians predict how rapidly the cancer is likely to spread. Higher Gleason scores are associated with more advanced and more rapidly growing cancers than lower scores.
Prostate-specific antigen blood test: PSA is a protein that is normally secreted and disposed of by the prostate gland. In patients with a known diagnosis of prostate cancer, the PSA level roughly reflects the total amount of cancer. The higher the PSA level, the more likely that the cancer is advanced.
Genomic testing helps individualize treatment. This means that patients with more serious conditions can be identified and offered aggressive and innovative therapies that may prolong their lives, while patients who are diagnosed with a less serious condition may be spared unnecessary treatments. Physicians have begun to propose that germline testing be performed for all patients at the time of prostate cancer diagnosis, even those with low-risk disease.
Overall 60% of men who report no risk factors like a family history of prostate cancer will have a genetic mutation. Universal testing should be considered for all men diagnosed with cancer of any grade or stage. Genetic testing is inexpensive and can identify germline mutations associated with prostate cancer risk and aggressiveness including BRCA2, ATM and MSH2 mutations.
Individuals at high genetic risk for prostate cancer should be followed more carefully based on the interim results from the IMPACT trial (Identification of Men with a genetic predisposition to ProstAte Cancer) which demonstrated that targeted screening in men at higher genetic risk with mutated BRCA2 genes can identify more men with higher-grade disease.
Individuals at higher genetic risk with a BRCA2 mutation have are more likely to have higher grade tumors and metastatic more lethal cancers. They should discuss whether they might benefit from more active surveillance (more frequent biopsies) with their managing physician. Additionally there are newer precision cancer medicines available to treat individuals with specific cancer driving mutations.
Genomics - OncotypeDX A genomic test—the Oncotype DX® Prostate Cancer test can measure the aggressiveness of prostate cancer and may help some men choose between immediate treatment or active surveillance.
The Oncotype DX prostate cancer test measures the level of expression of 17 genes across four biological pathways to predict prostate cancer aggressiveness. The test results are reported as a Genomic Prostate Score (GPS) that ranges from 0 to 100 and is combined with other clinical factors to further clarify a man’s risk prior to treatment intervention.