Christopher Dolinsky, MD
Updated by Lara Bonner Millar, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: April 7, 2011
The prostate is a small gland that only men have. It is normally about the size of a walnut. The prostate is located underneath the bladder and in front of the rectum. Because the prostate is close to the rectum, it can be felt by a doctor during a digital rectal exam (the part of a routine physical exam where the doctor inserts a gloved, lubricated finger into a man's anus). The prostate makes and stores fluid that is part of semen, and this fluid is released from a man's penis during ejaculation. The prostate is signaled to do its job by the male hormone testosterone, which can influence the behavior of the prostate gland and prostate cancer. Nerves to the penis, which are important in producing and maintaining an erection, run very close to the prostate. The prostate completely encircles the tube that carriers urine from the bladder to the penis, called the urethra. If the prostate enlarges, it can block the flow of urine from the bladder, making it difficult for a man to urinate.
Prostate cancer happens when cells in the prostate begin to grow out of control and can then escape out of the prostate to invade nearby tissues or spread throughout the body. Usually, prostate cancer is a slow-growing cancer that does not progress outside of the prostate gland at the time of diagnosis. However, sometimes it will grow quickly and spread to nearby lymph nodes. Lymph nodes are small, pea-sized pieces of tissue that filter and clean lymph, a clear liquid waste product. If prostate cancer has spread to your lymph nodes when it is diagnosed, it means that there is higher chance that it has spread to other areas of the body as well. If and when prostate cancer cells gain access to the bloodstream, they can deposit in various bones throughout the body, at which point the prostate cancer is said to have metastasized to the bones. This can occur if one has a variant of prostate cancer that is not slow-growing, but rather faster-growing and more aggressive in its behavior.
Every man is at risk for prostate cancer as he ages. Although prostate cancer can strike younger men, the risk of getting prostate cancer increases with age, and more than 70% of men diagnosed with prostate cancer are over the age of 65. Prostate cancer is the most common cancer diagnosed in men in the United States, after non-melanoma skin cancer. The American Cancer Society estimated 217,730 new cases of prostate cancer and 32,000 deaths from prostate cancer in the year 2010 in the United States.
Although there are several known risk factors for getting prostate cancer, no one knows exactly why one man gets it and another doesn't. Some of the most important risk factors for prostate cancer include age, ethnicity, genetics and diet. Age is generally considered the most important risk factor for prostate cancer. The incidence of prostate cancer rises quickly after the age of 60, and the majority of men will have some form of prostate cancer after the age of 80. One of the sayings about prostate cancer is that older men (over the age of 80) are more likely to die with prostate cancer than from prostate cancer. This saying means that many older men have low-volume, slower-growing prostate cancer disease that is not going to affect life expectancy because the cancer will take a very long time to grow and become clinically important. However, this saying is only a generalization; sometimes prostate cancer can grow quickly even in older patients.
Another important risk factor for prostate cancer is ethnicity. No one knows exactly why, but prostate cancer is more common in African-American and Latino men than Caucasian men. African-American men have a 1.6 fold higher chance of getting and dying from prostate cancer than Caucasian men. Asian and Native American men have the lowest chances of getting prostate cancer. Some doctors believe that genetic differences are important in explaining the different rates of prostate cancer between different ethnic groups; however, there is some evidence that differences in diets may be the cause. When Asian men move to Western countries like the United States, their chances of getting prostate cancer rise. Men who live in the United States and Northern Europe have the highest rates of prostate cancer, while men who live in South America, Central America, Africa, and Asia all have much lower chances of developing prostate cancer.
There is some evidence that a man's diet may affect his risk of developing prostate cancer. The most common dietary culprit implicated in raising prostate cancer risk is a high fat diet, particularly a diet high in animal fats. Also, a few studies have suggested that a diet low in vegetables causes an increased risk of prostate cancer. There are a few foods that have been implicated in decreasing prostate cancer risk: a diet high in tomatoes (lycopene) has been suggested as well as diet high in omega-3-fatty acids (oils found in fish like salmon and mackerel). Doctors and scientists aren't in full agreement as to the usefulness of eating these foods when it comes to decreasing prostate cancer risk. Diets high in selenium, vitamin D, and soy have all been suggested to decrease prostate cancer risk; but these are currently under study and data from large trials is needed before firm recommendations can be given about their use for this purpose.
A family history of prostate cancer increases a man's chances of developing the disease. This increase shows itself when a man has either a father or brothers (or both) with prostate cancer, and is even greater when his relatives develop prostate cancer at a young age. A variety of different genetic factors are currently being researched. Variations and mutations in certain genes may be responsible for some increases in prostate cancer rates in families. Men who carry mutations in genes known as BRCA1 or BRCA2 (these are genes implicated in breast and ovarian cancer in women) may have a 2 to 5 fold increase in prostate cancer risk. Men with high levels of testosterone or a hormone known as IGF-1 (insulin-like growth factor 1) seem to be at a higher risk for developing prostate cancer as well.
Because prostate cancer is a common disease and often has a very slow growing course, there is a lot of interest in trying to prevent prostate cancer with drugs, foods, or nutrients. Even a compound that could slow the progression of the disease could potentially decrease mortality. Right now, the best way to try and prevent prostate cancer is to modify the risk factors for prostate cancer that you have control over. You may want to try to eat a low fat diet that is rich in fruits and vegetables. Although certain foods, vitamins and minerals have been suggested to decrease your chances for getting prostate cancer, doctors still need more data before any particular food or supplement can be endorsed for preventing prostate cancer. Currently, there are studies looking at selenium, lycopene, vitamin A and other retinoids, vitamin D, vitamin E, and soy for prostate cancer prevention.
There is also interest in preventing prostate cancer by using drugs. We know that hormones like testosterone can cause prostate cancers to grow and develop, so there are experiments looking at drugs that can decrease the levels of testosterone in the prostate to attempt to stop prostate cancer from forming and growing. Drugs like Flutamide and Finasteride work in this manner, and they are currently under investigation for prostate cancer prevention, but are not routinely recommended as chemoprevention. Another way to decrease testosterone in the prostate is to decrease the total amount of testosterone in the body. Drugs that decrease total body testosterone have a whole host of undesirable side effects (drugs that do this are currently used to treat men who have already developed prostate cancer and will be discussed later in the treatment section), so they aren't nearly as good choices for prostate cancer prevention
Whether or not men should be screened for prostate cancer is an intensely debated issue. We know that prostate cancer usually grows very slowly, so intuitively it would make sense that we could reduce mortality from prostate cancer by picking it up early so it could be treated before it spreads. However, in order for a screening test to be fully embraced, we need to prove that picking up a disease early actually does help reduce the number of deaths. Right now, there are no good data showing that screening for prostate cancer reduces deaths from prostate cancer. There are currently very large trials in progress to see which populations of men will benefit most.
Currently, there are two methods that physicians use to screen for prostate cancer. One of them is called a digital rectal exam (DRE). A digital rectal exam is done in your primary care physician's office. Because your prostate is so close to your rectum, your doctor can feel it by inserting a gloved, lubricated finger into your anus. Your doctor can feel if there are lumps, asymmetries, or if your prostate is enlarged. A digital rectal exam is uncomfortable, but not painful. It is a useful test, but it is not perfect because some small cancers can be missed and only the bottom and sides of the prostate can be examined in this manner. Although it isn't a perfect test, it becomes more useful when it is combined with another test called a PSA.
A PSA (prostate specific antigen) test is a blood test that looks for this specific protein that is only made in the body by the prostate gland. Normal prostate tissue makes some background , but prostate cancer usually makes much more, and keeps making it, such that the PSA level keeps rising. By checking to see if your PSA is elevated, your doctor can screen you for prostate cancer. The PSA test isn't perfect either, because some tumors won't elevate the PSA, while some other processes (like benign prostatic hyperplasia and prostatitis) can cause it to be falsely elevated. However, the higher your PSA is, the more likely the elevation is to be caused by a prostate cancer. The cut-off that your doctor usually uses is 4.0 ng/ml, meaning that anything below 4.0 ng/ml is considered likely normal and anything above it is abnormal and may warrant a prostate biopsy. If your PSA is elevated, or you have an abnormal digital rectal exam, then you need to get further evaluation; however, this doesn't necessarily mean that you have prostate cancer. The only way to know for sure whether or not you have cancer is to get a sample of your prostate via a biopsy.
Both a digital rectal exam and a PSA blood level are simple, non-invasive tests. Most physicians recommend screening for prostate cancer with these tests in men with a life expectance of 10 years or more. However, some doctors don't think screening for prostate cancer is worth doing. One of the downsides is that you may go through an extensive workup and treatment for a disease that never would have shortened your life. We know that some prostate cancers are very slow growing (often taking more than 10 years to become significant), so if your life expectancy is less than 10 years it may not be worthwhile to go through the process of screening, biopsy and treatment. The treatment options for prostate cancer are not completely benign, and all of them have the potential for side effects. However, it is difficult for physicians to determine which prostate cancers will progress versus those that will remain indolent in any individual patient. Another argument against prostate cancer screening is that it has never been proven to save lives in studies of large populations in both the United States and Europe. However, many doctors think that newer treatments for early stage prostate cancers may make this argument obsolete. Data from large trials currently being carried out should help to settle this argument in the near future.
The American Cancer Society recommends that men make an informed decision on whether or not they should be screened after discussing with their physician the risks and benefits of screening. Screening is not recommended in men without symptoms of prostate cancer if they have a life expectancy of less than ten years. American Cancer Society recommends that men who choose to be tested start getting annual PSAs and digital rectal exams starting at age 50, unless they are high-risk (meaning they have a family history of prostate cancer or are African-American), who should begin screening at age 45. However, they mention that screening should only be carried out if your life expectancy is greater than 10 years, so men in their 80s and 90s (especially if they have other serious medical problems) should probably not be screened. The most important thing is to discuss the issue with your doctor. Decisions about screening should be individualized and reached after hearing about the potential benefits and harms of screening, biopsy and treatment.
Most early prostate cancers are detected with PSA tests or digital rectal exams before they cause any symptoms. However, more advanced prostate cancers can cause a variety of symptoms including:
All of these symptoms can be caused by a variety of things besides prostate cancer, so experiencing them doesn't necessarily mean you have prostate cancer. When older men have problems urinating, it is usually caused by process called benign prostatic hyperplasia (BPH) which is not prostate cancer. If you experience any of these symptoms, you need to see your doctor for evaluation.
If you have symptoms suspicious for a prostate-related problem, your doctor will do a digital rectal exam and a PSA blood test. If either of those two tests are abnormal, then most likely your doctor will recommend that you receive a prostate biopsy. Also, your doctor may want to get a biopsy if there is an abnormal result on a screening PSA or routine digital rectal exam. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to get cells that can be examined under a microscope. The most common way that a biopsy is done is with a transrectal ultrasound (TRUS). A transrectal ultrasound is a thin cylinder that emits sound waves and monitors them when they bounce off of tissue. It is inserted into your rectum, and allows your doctor to view your prostate and choose where to remove tissue from. Any suspicious areas are biopsied, plus some tissue will be removed from all of the different parts of the prostate (to make sure they don't miss any cancers that may be small and growing in one particular area). The procedure is done while you are awake, with the help of some numbing medicine. Unfortunately, a transrectal ultrasound isn't a perfect tool because even though many samples are taken, it can occasionally miss the area of the cancer. If this happens, and your PSA remains elevated, you may need to have the procedure repeated.
Once the tissue is removed, a doctor known as a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, then the pathologist will characterize it by what type of prostate cancer it is and how abnormal it looks (known as the grade). The vast majority of all prostate cancers (at least 95%) are a subtype known as adenocarcinoma, but occasionally they can be small cell carcinomas or lymphomas (two rare types of prostate cancer that are treated differently than the more standard adenocarcinomas). The pathologist then characterizes how much the cancer looks like normal prostate tissue, and this is known as the grade of the tumor. Pathologists often use a scale when they grade prostate tumors known as the Gleason score. The Gleason score runs from 2 to 10, with 2 being a very normal looking tumor and 10 being a very abnormal looking tumor. Generally, the more abnormal the tumor looks, the more aggressive it is. We characterize grades on a scale because, together with staging, it gives us a way to offer a prognosis and it often guides our choice of therapy.
Prostate cancer is divided into four different stages to help guide our treatments and offer information about the chances for a cure. This staging is done in a limited fashion before surgery taking into account whether or not the tumor can be felt on digital rectal exam and the results of any imaging modalities; it is done definitively after a surgical procedure that removes lymph nodes and allows a pathologist to examine them for signs of cancer. The staging system is somewhat complex, but here is a simplified version of it:
Although the clinical stage is important, the pathological stage is a more accurate predictor of the extent of your cancer because it actually examines the prostate and the lymph nodes in the area. If your stage, grade, and/or PSA are high enough, you may be referred for other tests before treatment to look for spread to other parts of your body. Tests like CT scans (a 3-D x-ray) or MRIs (like a CT scan but done with magnets) can examine the prostate and localized lymph nodes. Some patients are referred for a bone scan, which is a test using a radioactive tracer to look for metastasis to any of your bones. Another test that you may be referred for is called a ProstaScint scan, which uses a radioactive tracer that can localize prostate cancer cells within either bones or lymph nodes. Finally, if your doctors are very worried about spread to lymph nodes, they may choose to perform a surgical lymph node sampling before proceeding with any definitive treatment.
There are many different ways to treat prostate cancer, and you will most likely be consulting multiple types of doctors before making a final decision. Physicians are not always in agreement as to the way to proceed because there haven't been enough large trials that compare the different treatment modalities. For prostate cancer, it is important that you get a second opinion and you should talk to both urologists and radiation oncologists to hear about the benefits and risks of surgery, hormonal therapy and radiation in your particular case. If your prostate cancer has already spread at the time of diagnosis, you will also need a medical oncologist to talk about chemotherapy. The most important thing is to discuss your options and make a decision that suits your lifestyle, beliefs and values.
Surgery is a common form of treatment for men with prostate cancer. Surgery attempts to cure prostate cancer by removing the entire prostate and getting all of the cancer out of the body. An attempt at a surgical cure for prostate cancer is usually done with early stage prostate cancers, but sometimes surgery will be used to relieve symptoms in advanced stage prostate cancers. Surgery for prostate cancer is generally felt to be equivalent to radiation for prostate cancer in terms of survival, especially in early stage, low to intermediate grade cancers. The decision to have surgery versus radiation is often made on the basis of the patient's age and health status; the two different approaches have different side effect profiles depending on the patient's age.
The most common surgical procedure for prostate cancer is known as a radical prostatectomy. Radical prostatectomy means that the entire prostate gland is removed from around the tube that connects the bladder to the penis (the urethra). This surgery can be done in two different ways, the retropubic approach and the perineal approach. The retropubic approach means that incision in made in the lower abdomen, while the perineal approach means that the incision is made between the scrotum and the anus. Often times during a retropubic approach, the surgeon will remove some lymph nodes in the area and have them quickly examined by a pathologist for signs of cancer. If the nodes have cancer, then the surgeon will not to proceed with the operation. This is the major reason a retropubic approach is used in most surgeries today.
Radical prostatectomies are very safe surgeries with few life threatening complications; however, there is a significant risk for other side effects. Both urinary incontinence (not being able to hold in your urine) and impotence (inability to achieve and maintain an erection) are commonly associated with this procedure. Sometimes, particularly with lower grade and smaller cancers, a nerve sparing prostatectomy can be performed. This type of prostatectomy can decrease the chance that you will be impotent after the procedure. However, there is always a risk and not every patient is a candidate for a nerve sparing prostatectomy. The risk for impotency and incontinence increases with age; this is why younger men are often recommended to have surgery while older men are recommended to have radiation. The skill of your particular surgeon influences your chances of having these side effects during a radical prostatectomy.
Another surgical approach, which is being used more and more commonly is the robot-assisted radical prostatectomy (RAP). As with non-robotic prostatectomy techniques, the entire prostate is removed. To perform the procedure, several tiny incisions are made in the patient's abdomen and long, thin laparoscopic instruments are inserted and attached to the robot. The robot moves the instruments according to the instruction of the urologist who is seated at the robotic console. Therefore, the surgeon is controlling the movement of the robot the whole time. The rationale for this approach is that the slender arms of the robot can reach places and turn at angles that a surgeon’s hand cannot. RAP has some advantages over traditional prostatectomy techniques, which include decreased blood loss and shorter hospitalization and recovery, but is more costly, and also carries the risks of impotence and incontinence. Because RAP is relatively new, we do not know yet if cancer cure rates with RAP are equivalent to traditional radical prostatectomy. Of course, as with all surgical techniques, success will depend in part on the skill and experience of the surgeon.
Talk to your surgeon about their complication rates before your operation. With surgery, urinary incontinence and impotence are often most severe right after the operation and generally get better with time. There are things that your doctors can recommend to help you with either of these problems. Talk to your urologist about your options.
Prostate cancer commonly is treated with radiation therapy. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation therapy is another option besides surgery for early stage prostate cancer; and when advanced stage prostate cancer needs to be treated, it is usually done with radiation therapy. Radiation helps avoid surgery in patients who are too ill to risk having anaesthesia. Radiation is usually offered to older patients in the case of early stage prostate cancer because of its side effect profile may be more favorable than surgery in the elderly. Radiation can have impotence rates similar to surgery, but the risk of urinary incontinence is very low. Impotence develops months to years after the radiation treatment, unlike with surgery, which tends to have the side effects occur immediately. Other side effects from radiation include bladder irritation, which can cause urinary frequency and urgency as well as bladder pain, and diarrhea or rectal bleeding. Your radiation oncologist tries to limit the amount of radiation to other organs, but often the bladder and rectum can get some dosage because they are in such close proximity to the prostate.
Radiation therapy for prostate cancer either comes from an external source (external beam radiation) or an internal source where small radioactive seeds are implanted into the patient's prostate (brachytherapy). External beam radiation therapy requires patients to come in 5 days a week for up 6-9 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Brachytherapy is done as a one-time insertion, in the operating room. Brachytherapy cannot be done in all patients and is usually reserved for early stage prostate cancers. Your radiation oncologist can answer questions about the utility, process, and side effects of both of these types of radiation therapy in your particular case.
Another form of external beam radiation therapy for prostate cancer uses protons rather than x-rays to kill tumor cells. Protons are the positively charged components within the nucleus of an atom. They are used to deliver radiation because they deposit most of their cell-killing energy within the tumor site (in this case, the prostate gland), thus delivering less dose to the tissues where the proton beams entered, and virtually no dose beyond the area being treated (so-called "exit dose"). Because of the potential to decrease dose deposition within normal tissues, many researchers are interested in learning whether treatment with protons has fewer and/or less severe long-term side effects compared to standard x-ray radiation treatments. Protons may have a theoretical advantage, but so far there is little evidence to "prove" that they superior. In fact not even surgery and radiation have been compared head to head, let alone proton radiation and x-ray radiation. To determine which treatment is best, large numbers of men would have to participate in a randomized trial, and be followed for several years to determine outcomes. Even though there are many challenges to carrying out this kind of study, the investigations into proton therapy continue to move forward. Lean more about proton therapy in this Proton Therapy: the Basics article.
Both normal prostate tissue and prostate cancers depend on male sex hormones, called androgens, to grow and replicate. Testosterone is an androgen very important to the prostate gland. Men make androgens in their testicles. One of the ways to treat prostate cancer is to remove androgens from the body, thus making the cancer shrink and then grow more slowly. There are a few different ways to remove androgens: you can remove a man's testicles (called an orchiectomy), you can give a man drugs that block the production of androgens (called LHRH agonists), you can give a man drugs that block androgen receptors (called anti-androgens) or you can give a man estrogens. Different methods of deceasing androgens are often used in the same patient: using LHRH agonists with anti-androgens can achieve what is known as a total androgen blockade. Hormone therapy can also be used in conjunction with other treatments, especially in the case of advanced stage prostate cancer being treated with radiation therapy. In that case, hormonal therapy is often given before the radiation and this is known as neoadjuvant hormonal therapy. Another use for hormones is in patients who present with metastatic disease. After a while, all prostate cancers will become resistant to hormonal therapy. However, this often takes many years and hormonal therapy can buy a lot of time in patients with extensive disease or patients who choose not to undergo surgery or radiation.
There are a number of side effects associated with hormonal therapy. Hormonal therapy will almost universally cause impotence and the loss of your sex drive. It can also cause breast enlargement, hot flashes, and muscle and bone loss (osteoporosis). There are some things your doctors can prescribe to help with bone loss and hot flashes, but little can be done about loss of libido and impotence.
Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. Chemotherapy is prescribed by medical oncologists, who are experts at choosing appropriate regimens for particular patients. Chemotherapy for prostate cancer is generally only reserved for very advanced cancers that are no longer responsive to hormonal therapy. There are a number of chemotherapy drugs that can be used for prostate cancer, and they are often used in combinations. A common chemotherapy regimen is Mitoxantrone with Coritcosteroids; and other regimens that are becoming increasingly popular use a drug called Estramustane with drugs called Taxanes (paclitaxel). The use of chemotherapy in prostate cancer is currently being studied and men who get chemotherapy are encouraged to talk to their doctors about experimental trials. There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your lifestyle
Sipuleucel-T (Provenge) was approved in 2010 as a treatment of metastatic prostate cancer when the cancer longer responds to hormonal treatments. It is a form of immunotherapy that involves harvesting a specific type of the patient’s own white blood cell and combining the cells with a protein called prostatic acid phosphatase (PAP) found on prostate cancer cells, in order to activate the white blood cells. The cells are then given back to the patient about 3 days later, in a process similar to a blood transfusion. A treatment is given 3 times, with about 2 weeks in between each dose. This drug can increase survival by a few months, in men who are in good health. Possible side effects include fever, nausea, and headaches.
Cryosurgery is a somewhat experimental approach to treating prostate cancer whereby probes with liquid nitrogen are implanted into the prostate and then the tissue is frozen. This freezing kills the cancer cells, and it can be repeated multiple times if needed. However, data to date has shown that cryosurgery is not as effective as radiation and surgery for treating prostate cancer. Cryosurgery also has a variety of side effects including urinary incontinence and impotence.
Some patients choose to receive no therapy for their prostate cancer in the hopes that it will grow very slowly. By avoiding any therapy, they avoid the side effects that come along with surgery, radiation, or hormones. Active surveillance is appropriate for older men with small, low-grade tumors, and slowly rising PSAs, and multiple other medical problems. Active surveillance can be considered in patients who have a life expectancy less than 10 years as long as the cancer isn't large or of a high grade. Men who choose to undergo watchful waiting should have PSAs and digital rectal exams done every 3-6 months, and need to be re-biopsied at some point to make sure the grade hasn't become less favorable. However, it is never really clear what change in clinical status should institute treatment. Also, if the tumor has progressed, they may no longer be eligible for curative therapy.
Once a patient has been treated for prostate cancer, they need to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your doctor will tell you when he or she wants follow-up visits, PSAs and x-rays or scans depending on your case. Your doctor will also probably do digital rectal exams regularly during your office visits. It is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments.
Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.
This article is meant to give you a better understanding of prostate cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about prostate cancer on OncoLink through the related links to the left.