Prostate Cancer

What is Prostate Cancer?

Prostate cancer occurs when cells within the prostate grow uncontrollably, creating small tumors.  The term “cancer” refers to a condition in which the regulation of cell growth is lost and cells grow uncontrollably.  Most cells in the body are constantly dividing, maturing and then dying in a tightly controlled process.  Unlike normal cells, the growth of cancer cells is no longer well-regulated.  Instead of dying as they should, cancer cells outlive normal cells and continue to form new, abnormal cells.

Abnormal cell growths are called tumors.  The term “primary tumor” refers to the original tumor; secondary tumors are caused when the original cancer spreads to other locations in the body.  Prostate cancer typically is comprised of multiple very small, primary tumors within the prostate.  At this stage, the disease is often curable (rates of 90% or better) with standard interventions such as surgery or radiation that aim to remove or kill all cancerous cells in the prostate.  Unfortunately, at this stage the cancer produces few or no symptoms and can be difficult to detect.

What is Metastatic Prostate Cancer?

If untreated and allowed to grow, the cells from these tumors can spread in a process called metastasis.  In this process, prostate cancer cells are transported through the lymphatic system and the bloodstream to other parts of the body, where they lodge and grow secondary tumors.  Once the cancer has spread beyond the prostate, cure rates drop dramatically.

In most cases, prostate cancer is a relatively slow-growing cancer, which means that it typically takes a number of years for the disease to become large enough to be detectable, and even longer to spread beyond the prostate.  This is good news. However, a small percentage of patients experience more rapidly growing, aggressive forms of prostate cancer.  Unfortunately, it is difficult to know for sure which prostate cancers will grow slowly and which will grow aggressively – complicating treatment decisions.

The spread of cancer outside the prostate can be detected by the presence of prostate cancer cells in areas surrounding the prostate such as the seminal vesicle, lymph nodes in the groin area, the rectum and bones.  When prostate cancer spreads to another site, such as bone, the new tumor is still considered to be prostate cancer, not bone cancer.

How Common is Prostate Cancer?

It is the most common non-skin cancer in America, affecting 1 in 6 men. A non-smoking man is more likely to develop prostate cancer than he is to develop colon, bladder, melanoma, lymphoma and kidney cancers combined. In fact, a man is 35% more likely to be diagnosed with prostate cancer than a woman is to be diagnosed with breast cancer.

In 2009, more than 192,000 men will be diagnosed with prostate cancer, and more than 27,000 men will die from the disease. One new case occurs every 2.7 minutes and a man dies from prostate cancer every 19 minutes.

It is estimated that there are more than 2 million American men currently living with prostate cancer.

How curable is prostate cancer?

As with all cancers, "cure" rates for prostate cancer describe the percentage of patients likely remaining disease-free for a specific time. In general, the earlier the cancer is caught, the more likely it is for the patient to remain disease-free.

Because approximately 90% of all prostate cancers are detected in the local and regional stages, the cure rate for prostate cancer is very high—nearly 100% of men diagnosed and treated at this stage will be disease-free after five years. By contrast, in the 1970s, only 67% of men diagnosed with local or regional prostate cancer were disease-free after five years.

Yet being diagnosed with prostate cancer can be a life-altering experience. It requires making some very difficult decisions about treatments that can affect not only the life of the man diagnosed, but also the lives of his family members in significant ways for many years to come.

 

Risk Factors

Prostate cancer is the most common non-skin cancer in America, affecting 1 in 6 men. The older you are, the more likely you are to be diagnosed with prostate cancer. Although only 1 in 10,000 under age 40 will be diagnosed, the rate shoots up to 1 in 38 for ages 40 to 59, and 1 in 15 for ages 60 to 69. In fact, more than 65% of all prostate cancers are diagnosed in men over the age of 65.

But the roles of race and family history are important as well. African American men are 61% more likely to develop prostate cancer compared with Caucasian men and are nearly 2.5 times as likely to die from the disease. Men with a single first-degree relative—father, brother or son—with a history of prostate cancer are twice as likely to develop the disease, while those with two or more relatives are nearly four times as likely to be diagnosed. The risk is even higher if the affected family members were diagnosed at a young age, with the highest risk seen in men whose family members were diagnosed before age 60. (When weighing risk factors for prostate cancer, it’s also important to recognize that there are non-risk factors, or factors that have not been linked to an increase in risk.)

Although genetics might play a role in deciding why one man might be at higher risk than another, social and environmental factors, particularly diet and lifestyle, likely have an effect as well.

In fact, research in the past few years has shown that diet modification might decrease the chances of developing prostate cancer, reduce the likelihood of having a prostate cancer recurrence, or help slow the progression of the disease.

PSA & DRE Screening

The purpose of screening for cancer is to detect the cancer at its earliest stages, before any symptoms have developed.

Some men, however, will experience symptoms that might indicate the presence of prostate cancer. Because these symptoms can also indicate the presence of other diseases or disorders (such as BPH orprostatitis), these men will undergo a more thorough work-up. Typically, men whose prostate cancer is detected through screening are found to have very early-stage disease that can be treated most effectively.

Screening for prostate cancer can be performed quickly and easily in a physician’s office using two tests: the PSA (prostate-specific antigen) blood test, and the digital rectal exam (DRE).

The PSA Blood Test

PSA is a protein produced by the prostate and released in very small amounts into the bloodstream. When there’s a problem with the prostate, such as when prostate cancer develops and grows, more and more PSA is released, until it reaches a level where it can be easily detected in the blood.

During a PSA test, a small amount of blood is drawn from the arm, and the level of PSA is measured. PSA levels under 4 ng/mL are usually considered "normal," results over 10 ng/mL are usually considered "high," and results between 4 and 10 ng/mL are usually considered "intermediate."

However, PSA can also be elevated if other prostate problems are present, such as BPH or prostatitis, and some men with prostate cancer have "low" levels of PSA. This is why both the PSA and DRE are used to detect the presence of disease.

The Digital Rectal Exam

During a DRE, the physician inserts a gloved, lubricated finger into the rectum and examines the prostate for any irregularities in size, shape, and texture. Often, the DRE can be used by urologists to help distinguish between prostate cancer and non-cancerous conditions such as BPH.

Should I Be Screened?

The American Urological Association (AUA) Foundation recommends that all men over 40 should speak with their doctors at the the time of their annual physicals and develop a proactive prostate health plan that is right for them based on their lifestyles and family history.  The AUA also recommends getting a baseline PSA along with a DRE at age 40.

There is no unanimous opinion in the medical community regarding the benefits of prostate cancer screening. Those who advocate regular screening believe that finding and treating prostate cancer early offers men more treatment options with potentially fewer side effects. Those who recommend against regular screening note that because most prostate cancers grow very slowly, the side effects of treatment would likely outweigh any benefit that might be derived from detecting the cancer at a stage when it is unlikely to cause problems.

Because a decision of whether to be screened for prostate cancer is a personal decision, it's important that each man talk with his doctor about whether prostate cancer screening is right for him.

Diagnosis (Gleason Scores and Staging the Disease)

Although the DRE and PSA tests cannot diagnose prostate cancer, they can signal the need for a biopsy to examine the prostate cells and determine whether they are cancerous. In some men, changes in urinary or sexual function lead to a full evaluation by the doctor, and, if prostate cancer is suspected, a biopsy will be performed.

The Biopsy

During a biopsy, needles are inserted into the prostate to take small samples of tissue, often under the guidance of ultrasound imaging. The biopsy procedure may cause some discomfort or pain, but the procedure is short, and can usually be performed without an overnight hospital stay.

Gleason Grading and Gleason Scores

Under normal conditions, prostate cells, just like all other cells in the body, are constantly reproducing and dying, and each new prostate cell has the same shape and appearance as all of the other prostate cells. But cancer cells look different, and the degree to which they look different from normal cells is what determines the cancer grade. "Low-grade" tumor cells tend to look very similar to normal cells, whereas "high-grade" tumor cells have mutated so much that they often barely resemble the normal cells.

The Gleason grading system accounts for the five distinct patterns that prostate tumor cells tend to go through as they change from normal cells. The scale runs from 1 to 5, where 1 represents cells that are very nearly normal, and 5 represents cells that don’t look much like prostate cells at all.

After examining the cells under a microscope, the pathologist looking at the biopsy sample assigns one Gleason grade to the most common pattern, and a second Gleason grade to the next most common pattern. The two grades are added, and the Gleason score, or sum, is determined.

Generally speaking, the Gleason score tends to predict the aggressiveness of the disease and how it will behave. The higher the Gleason score, the less the cells behave like normal cells, and the more aggressive the tumor tends to be.

Staging the Disease

Staging determines the extent of prostate cancer. Localized prostate cancer means that the cancer is confined within the prostate. Locally advanced prostate cancer means that most of the cancer is confined within the prostate, but some has started to escape to the immediate surrounding tissues. In metastatic disease, the prostate cancer is growing outside the prostate and its immediate environs, possibly to more distant organs.

A number of tests can be used to help determine the stage of disease. For example, cancers growing outside of the prostate can often be detected through traditional imaging studies, such as CT scans, MRIs, or x-rays, or through more specialized imaging tests such as bone scans. Note that because these tests cannot detect very small groups of cancer cells, results of these tests cannot be used alone to determine the stage of the disease, to guide treatment options, or to predict outcomes.

Metastatic disease can also be detected through imaging studies, and often can be detected in the lymph nodes. Cancers that spread to more distant organs tend to travel through the lymph system, a circulatory system similar to the blood stream that carries cells important in fighting infection and disease. During a biopsy, or, more often, during surgery, lymph nodes will be removed and examined for the presence of cancer cells.

Knowing the stage of disease can help to determine how aggressively the disease needs to be treated, and how likely it is to be eradicated by the available treatment options.

Prostate Cancer Treatment

There is no "one size fits all" treatment for prostate cancer, so each man must learn as much as he can about various treatment options and, in conjunction with his physicians, make his own decision about what is best for him.

For most men, the decision will rest on a combination of clinical and psychological factors. Men diagnosed with localized prostate cancer today will likely live for many years, so any decision that is made now will likely reverberate for a long time. Careful consideration of the different options is an important first step in deciding on the best treatment course.

Consultation with all three types of prostate cancer specialists—a urologist, a radiation oncologist and a medical oncologist—will offer the most comprehensive assessment of the available treatments and expected outcomes.

Click on the following for more information about particular treatment options for prostate cancer:

Active Surveillance

The concept of active surveillance, or watchful waiting, has increasingly emerged in the past years as a viable option for men who, for one reason or another, have decided not to undergo immediate surgery or radiation therapy. During active surveillance, the cancer is carefully monitored for signs of progression. APSA blood test and DRE are usually administered every six months along with a yearly biopsy of the prostate. If symptoms develop, or if tests indicate that the cancer is growing, treatment might be warranted.

Active surveillance might be a good choice for men who have very slow growing or very early cancers,  or for men who have other serious medical conditions that affect the way they live their lives, especially if these other conditions are likely to shorten their lifespan.

Also, many of the treatment options for prostate cancer can be difficult to endure, and better outcomes are seen in men who are otherwise healthy. If a man is currently battling other disorders or diseases, such as heart disease, long-standing high blood pressure, or poorly controlled diabetes, his doctors might feel that it is in his best interest to hold off on therapy and avoid its potential complications.

Prostatectomy (Surgery) Prostatectomy (Surgery)

A surgical approach toward the treatment of prostate cancer can be used to remove all or part of the prostate. Typically, men with early-stage disease or cancer that is confined to the prostate will undergo radical prostatectomy, or surgical removal of the entire prostate gland plus some surrounding tissue. This procedure is described below. Other surgical procedures may be performed on men with advanced or recurrent disease.

In the most common type of prostatectomy, known as radical retropubic prostatectomy, an incision is made in the abdomen and the prostate is cut out from behind the pubic bone. After removing the prostate, the surgeon stitches the urethra directly to the bladder so urine is able to flow. (Review the roles of the prostate and the surrounding organs in the About the Prostate section.)

Because it typically takes a few days for the body to get used to this new setup, the surgeon will insert a catheter, or tube, into the bladder. With this in place, urine flows automatically out of the bladder, down the urethra, and into a collection bag without the need for conscious control of the sphincter. The catheter is usually kept in place for about a week to 10 days.

Another type of surgery, known as radical perineal prostatectomy, is performed less frequently these days. In this approach, the surgeon makes the incision in the perineum, or the space between the scrotum and the anus, and the prostate is removed from behind.

Surgical Techniques

In a nerve-sparing prostatectomy, the surgeon cuts to the very edges of the prostate, taking care to spare the erectile nerves that run alongside the prostate. In cases when the nerves cannot be spared because the cancer extends beyond the prostate, surgically attaching, or grafting, nerves from other parts of the body to the ends of the cut erectile nerves might be possible.

In laparoscopic surgery, very small incisions are made in the abdomen, into which the surgeon inserts narrow instruments fitted with cameras and/or surgical tools, allowing the surgeon to visualize and operate on the internal structures without cutting open the entire abdomen. With a robotic interface, the surgeon maneuvers the robot’s arms, which in turn control the cameras and instruments inserted in the abdomen.

The Importance of Surgical Skill

Prostatectomy, like many surgical procedures, is very delicate work, and the difference between a good surgeon and a great surgeon can affect outcomes. When choosing a surgeon, at a minimum, ensure that he or she is someone in whom you have confidence, and someone who has enough experience to not only perform the operation, but to also make an informed clinical judgment and change course should the need arise. Radiation Therapy

External Beam Radiation Therapy
Proton Therapy
Brachytherapy

Radiation involves the killing of cancer cells and surrounding tissues with directed radioactive exposure. (Review the roles of the prostate and the surrounding organs in the About the Prostate section.)

The use of radiation therapy as an initial treatment for prostate cancer is described below. Some forms of radiation therapy can also be used in men with advanced or recurrent prostate cancer.

External Beam Radiation Therapy

The most common type of radiation therapy is external beam radiotherapy. CT scans and MRIs are used to map out the location of the tumor cells, and x-rays are targeted to those areas. With 3D conformal radiotherapy, a computerized program maps out the exact location of the prostate tumors so that the highest dose of radiation can reach the cancer cells within the gland.

Intensity-modulated radiation therapy (IMRT) allows oncologists to modulate, or change, the intensity of the doses and radiation beams to better target the radiation delivered to the prostate, while at the same time delivering lower doses to the tumor cells that are immediately adjacent to the bladder and rectal tissue.

Because the treatment planning with these types of radiation therapy are far more precise, higher—and more effective—doses of radiation can be used with less chance of damaging surrounding tissue.

Regardless of the form of external radiation therapy, treatment courses usually run five days a week for about seven or eight weeks, and are typically done on an outpatient basis.

Proton Therapy

While X-rays are currently the main method of treating tumors with radiation therapy, facilities that perform proton therapy are slowly becoming more commonplace. Worldwide, says Alfred R. Smith of the M. D. Anderson Cancer Center in Houston, there are more than six medical institutions with proton machines in the United States, and five more are in the planning or construction stages.

The advantage of using protons over other external beam sources is the precision with  which protons of energetic particles are aimed at a targeted prostate cancer tumor while not affecting surrounding tissue. This direct attack on cancerous cells ultimately causes their death as the cell is particularly vulnerable to attack due to their rapid cell division. Proton treatment is notably valuable for treating localized, isolated, solid tumors before they spread to other tissues and to the rest of the body.

However, issues of cost and access have hampered wider use. Today’s proton-therapy machines take up a considerable amount of room owing to the large magnets that create the energetic particles and the concrete walls that are needed to shield the radiation. These machines also come with a hefty cost—between $25 and $150 million—allowing only a handful of cancer centers the ability to purchasing such equipment.

As efforts are made to reduce the size of these machines, the cost to build them and the price tag for treatment should also fall—giving cancer patients more accessibility to this treatment option. A machine now being developed by researchers at Lawrence Livermore National Laboratory is expected to be a fifth of the size and cost of the proton-therapy machines that are currently found at six specialized medical centers in the United States.  Five more centers are currently under construction in the U.S.

Brachytherapy

With brachytherapy, tiny little metal pellets containing radioactive iodine or palladium are inserted into the prostate via needles that enter through the skin behind the testicles. As with 3D conformal radiation therapy, careful and precise maps are used to ensure that the seeds are placed in the proper locations.

Over the course of several months, the seeds give off radiation to the immediate surrounding area, killing the prostate cancer cells. By the end of the year, the radioactive material degrades, and the seeds that remains are harmless.

Compared with external radiation therapy, brachytherapy is less commonly used, but it is rapidly gaining ground, primarily because it doesn’t require daily visits to the treatment center.

The Importance of Dose Planning

Just as surgical skill can play an important role in determining outcomes from prostatectomy, technical skill and manual dexterity can play an important role in determining outcomes from radiation therapy. The use of computer software to assist with the dose planning and target prostate tissue helps greatly, but, in the end, the skill and experience of the radiation oncologist will make the biggest difference.

When choosing a radiation oncologist, at a minimum, make sure he or she has broad experience with an assortment of approaches and can objectively help to decide on the best course of treatment.

Hormone Therapy

Prostate cancer cells are just like all other living organisms—they need fuel to grow and survive. Because the hormone testosterone serves as the main fuel for prostate cancer cell growth, it is a common target for therapeutic intervention in men with prostate cancer.

Hormone therapy, also known as androgen-deprivation therapy or ADT, is designed to stop testosterone from being released or to prevent the hormone from acting on the prostate cells. Although hormone therapy plays an important role in men with advancing prostate cancer, it is increasingly being used before, during, or after local treatment as well.

The majority of cells in prostate cancer tumors respond to the removal of testosterone. But some cells grow independent of testosterone, and therefore remain unaffected by hormone therapy. As these hormone-independent cells continue to grow unchecked, over time, hormone therapies have less and less of an effect on the growth of the tumor.

Hormone therapy is therefore not a perfect strategy in the fight against prostate cancer, and does not cure the disease. But it remains an important step in the process of managing advancing disease, and will likely be a part of every man’s therapeutic regimen at some point during his fight against recurrent or advanced prostate cancer.

The most common types of hormone therapy are described below. Although each of these therapeutic options is effective at controlling prostate cancer growth, the loss of testosterone confers significant side effects in nearly all men. (A review of how best to manage side effects from testosterone loss can be found in the Side Effects section.)

Orchiectomy

Because about 90% of testosterone is produced by the testicles, surgical removal of the testicles, ororchiectomy, is an effective solution to blocking testosterone release. This approach has been used successfully since the 1940s, but because it’s a permanent and irreversible surgical solution, most men opt for drug therapy instead.

For men who choose this option, the procedure is typically done on an outpatient basis in the urologist’s office. Recovery tends to be rather quick and no further hormone therapy is needed, making orchiectomy a very attractive choice for someone who prefers a low-cost, one-time procedure.

LHRH Agonists

LHRH, or luteinizing-hormone releasing hormone, is one of the key hormones released by the body before testosterone is produced. (Note that LHRH is sometimes called GnRH, or gonadotropin-releasing hormone.) Blocking the release of LHRH through the use of LHRH agonists or LHRH analogues is one of the most common hormone therapies used in men with prostate cancer.

Drugs in this class, including leuprolide (Eligard, Lupron, and Viadur), goserelin (Zoladex), and triptorelin (Trelstar), are given in the form of regular shots: once a month, once every three months, once every four months, or once per year.

Antiandrogens

LHRH agonists cause what is known as a "flare" reaction because of an initial transient rise in testosterone. This can result in a variety of symptoms ranging from bone pain to urinary frequency or difficulty.

Antiandrogenssuch as bicalutamide (Casodex), flutamide (Eulexin), and nilutamide (Nilandron), help to block the action of testosterone in prostate cancer cells. They are therefore often added to the LHRH agonist for at least the first 4 weeks of therapy when the flare reaction typically occurs. In this setting, antiandrogens can be helpful in preventing the flare reaction.

 

Although the sexual side effects of the antiandrogens when given alone are typically far fewer compared with the LHRH agonists, antiandrogens might not be as effective as orchiectomy or LHRH agonists and are not the optimal choice for men with documented metastatic prostate cancer.

Chemotherapy

The term "chemotherapy" refers to any type of therapy that uses chemicals to kill or halt the growth of cancer cells. The drugs work in a variety of ways, but are all based on the same simple principle: stop the cells from dividing and you stop the growth and spread of the tumor.

Until recently, chemotherapy was used only to relieve symptoms associated with very advanced or metastatic disease. With the publication of two studies in 2004 showing that the use of docetaxel (Taxotere) can prolong the lives of men with prostate cancer that no longer responds to hormone therapy, more and more doctors are recognizing the potential benefits of chemotherapy for the men they treat with advanced prostate cancer.

Building on these successes, there are now dozens of clinical trials studying various combinations of chemotherapy drugs, some using new mixes of older drugs and some using newer drugs. Some trials are looking to find a chemotherapy regimen that’s more tolerable or more effective than docetaxel in men with metastatic disease, others are looking to find a chemotherapy regimen that can delay the onset of metastases, and still others are seeking to improve upon the results with docetaxel by adding to it other novel agents and testing the combination.

Paramount in all researchers’ minds is a way to maximize benefit while minimizing side effects.Chemotherapy, like all powerful drugs, can take a toll on the body. A review of how to best manage the side effects of chemotherapy can be found in the Side Effects section.

Off-Label Chemotherapy Use

Strictly speaking, few chemotherapy agents have been approved by the FDA for use in prostate cancer. But over the years, doctors have found that some medications that are regularly used in other types of cancers can be used rather effectively in men with prostate cancer.

Off label use of a drug means that the drug is approved by the FDA for use in one disease but is being used in another. The drug is known to be safe overall, and has been proven effective for the disease in which it’s approved. That doesn’t mean it’s not effective in prostate cancer as well; it just means that the drug hasn’t been rigorously tested in prostate cancer, so there’s no formal "proof" that it’s effective. Nevertheless, off-label use of chemotherapy is common, and its use is often found to be beneficial in men with prostate cancer.

Because very few drugs will score a home run in every person, second-line chemotherapy has a long and valued tradition in the treatment of cancer. In this setting, off-label drugs are common, and are chosen specifically because they work somewhat differently than what was used first, providing another chance to see a benefit.

Side Effects of Chemotherapy

Each of the chemotherapy drugs available today works in a slightly different fashion, and it’s hard to predict what sorts of side effects any one person will experience. But there are a few rules of thumb when it comes to chemotherapy that should always be kept in mind.

1) Ignore what others have said about their reactions to the different drugs—dosage, the combination of drugs, and the response to the drugs might be completely different. No two people are the same and no two cancers are the same, which means that no two people will react to the drugs in the same way.

2) Pay close attention to both expected and unexpected reactions to the different drugs. The doctors, nurses, and pharmacists will describe what to look out for in general, but it’s always possible to experience something that they didn’t anticipate. An unexplained side effect might be nothing, but it’s far better to be extra cautious than to ignore something that might be causing harm.

3) Don’t be "macho." There are plenty of drugs available to help ward off or treat the different side effects, including nausea/vomiting, sleep problems, and general exhaustion. All treatments work best when the body is at its strongest.

4) Relax. Chemotherapy drugs are powerful and can take a toll on the body. Focus on getting well by finding a way to relax—listening to music, doing yoga or stretching exercises, taking a walk in the woods or on the beach, or watching a movie marathon on television. Effectively relieving stress will help contribute to the ultimate goal of all cancer treatments—getting well.

Managing Bone Metastases and Pain

Prostate cancer cells that spread to the bone are known as prostate cancer bone metastases (not bone cancer). Once they settle in the bone, the cancer cells begin to interfere with the normal health and strength of the bones, often leading to bone pain, fracture, or other complications that can significantly impair one’s health.

Early detection of bone metastases can help to determine the best treatment strategy, and can help to ward off complications caused by the metastases.

In addition, because men with prostate cancer bone metastases often experience painful episodes, pain management and improving quality of life is an important part of all treatment strategies for men with bone metastases.