Prostate Cancer

Prostate cancer is the most commonly diagnosed solid organ tumor in men in the United States. In 2018, it is estimated that over 165,000 men will be diagnosed with prostate cancer, and more than 29,000 men will die from it. Prostate cancer is the second leading cause of cancer death in men after lung cancer.

Prostate cancer is cancer that occurs in the prostate — a small walnut-shaped gland in men that produces the seminal fluid that nourishes and transports sperm. Usually, prostate cancer grows slowly and is initially confined to the prostate gland, where it may not cause serious harm. However, while some types of prostate cancer grow slowly and may need minimal or even no treatment, other types are aggressive and can spread quickly.

Prostate cancer that’s detected early when it’s still confined to the prostate gland has a better chance of successful treatment.

Risk Factors

Risk factors for developing prostate cancer include:

• Age: Prostate cancer generally develops after the age of 50, with most cases diagnosed in men over the age of 65.
• Ethnicity: African and Caribbean-American men are twice as likely as American men of European ancestry to develop prostate cancer.
• Family History: Men with a father or brother with prostate cancer have an increased risk for developing the disease.
• Diet: Studies indicate that men who have a high-fat diet and who smoke have a greater chance of developing prostate cancer.

Symptoms

In its early stages, prostate cancer often has no symptoms. When symptoms do occur, they can be like those of an enlarged prostate or BPH. Thus, it is vital to talk to your healthcare provider when you have urinary symptoms.

Later symptoms include:

• Dull pain in the lower pelvic area
• Frequent urinating
• Trouble urinating, pain, burning, or weak urine flow
• Blood in the urine
• Painful ejaculation
• Pain in the lower back, hips or upper thighs
• Loss of appetite
• Loss of weight
• Bone pain

Evaluation and Diagnosis

Screening and Detection

Early-stage prostate cancers typically do not cause symptoms but may be found during routine screening exams, such as a digital rectal exam (DRE) and a prostate-specific antigen (PSA) blood test. Men typically begin prostate cancer screening at the age of 50, although men at high risk are encouraged to discuss screening with their doctor when they’re 40.

Digital Rectal Exam (DRE)

On physical examination, digital rectal exam (DRE) may detect prostate nodules, induration, or asymmetry that can occur with prostate cancer. However, prostate cancer is often not detectable by DRE, because DRE can only detect tumors in the posterior and lateral aspects of the prostate gland, which are the portions of the prostate that are palpable via the rectum. Tumors not detected by DRE include the 25 to 35 percent that are not reachable because they occur in other parts of the gland and the small, stage T1 cancers that are not palpable.

DRE is generally not recommended as a routine screening test for evaluation of the prostate or rectal area in the absence of symptoms (urinary or rectal). However, when an abnormality suggestive of prostate cancer is detected on DRE, further evaluation is warranted.

Prostate-Specific Antigen (PSA)

Prostate-specific antigen (PSA) is a glycoprotein produced by prostate epithelial cells. PSA levels may be elevated in men with prostate cancer because PSA production is increased and because tissue barriers between the prostate gland lumen and the capillary are disrupted, releasing more PSA into the serum.

The likelihood of prostate cancer increases with a more elevated PSA value. However, PSA is not specific for malignancy, and an elevated PSA can occur in a number of benign conditions; additionally, a PSA result in the normal range does not rule out the possibility of prostate cancer.

A positive PSA test is not a reason to panic; noncancerous conditions are the most common causes for an abnormal test. On the other hand, a positive test should not be ignored.

The first step in evaluating an elevated PSA is usually to repeat the test. In some cases, you may be treated for a prostate infection before repeating the test. Even if you are not treated for infection, you should avoid ejaculating and riding a bike for at least 48 hours before repeating the test. If the PSA remains elevated, a prostate biopsy or other testing is usually recommended.

Multiparametric Magnetic Resonance Imaging (mpMRI)

Prostate multiparametric magnetic resonance imaging (mpMRI) has emerged as the imaging method best able to detect clinically significant prostate cancer and to guide biopsy. The term “multiparametric” refers to the multiple MRI sequences that are analyzed to determine the diagnosis, which differs from other MRI scans in which the diagnosis is based on a single MRI sequence. In prostate mpMRI, no one MRI sequence is definitive; rather, it is the combination of positive parameters that contributes to the diagnosis.

Multiparametric MRI combines traditional anatomic imaging techniques with functional techniques to reveal detailed information about potential prostate cancers. Compared with conventional diagnostic tools used in prostate cancer detection and diagnosing, multiparametric MRI is proving to be useful in multiple phases of a more reliable option when it comes to determining which men would benefit from biopsy. Paired with prostate-specific antigen (PSA) screening, multiparametric MRI can be used to evaluate elevated and rising PSA levels prior to biopsy. Additionally, multiparametric MRI images can be used to guide biopsy needles with greater accuracy than other imaging techniques and can provide information to assist prostate cancer staging and treatment planning.

Transrectal Ultrasound (TRUS)

Ultrasound uses sound waves to visualize internal organs and evaluate them for cancer and other conditions. To create an image of your prostate, your doctor may perform a transrectal ultrasound (TRUS), which involves inserting a lubricated ultrasound probe into the rectum. TRUS is useful for determining the size of the prostate, but its most important function is to guide the needle during a prostate biopsy.

Prostate Biopsy

A biopsy is the only way to definitively diagnose prostate cancer. This procedure involves removing cells or tissue for microscopic examination by a pathologist (a doctor who specializes in the diagnosis of disease). A thin, hollow needle is inserted into the prostate through the wall of the rectum. It is then used to remove a small tissue sample. Several tissue samples are usually collected; typically, 6 to 12 samples are obtained. Taking this many samples helps ensure that the prostate cancer is found. Biopsies are usually performed at the doctor’s office.

Fusion Prostate Biopsy

This is a new method of biopsy that fuses, or combines, detailed MR images with live, real-time ultrasound images of the prostate. For this type of biopsy, an MRI is done first, and a radiologist notes any suspicious areas on the images. At another appointment, an ultrasound probe is inserted into the patient’s rectum. As the probe moves around the prostate, fusion software shifts an overlaid MR image accordingly, giving the doctor a detailed three-dimensional ultrasound/MRI view. The fused image helps guide the biopsy needles precisely to the suspicious areas.

A fusion biopsy pinpoints the area in question more precisely than a routine biopsy, which may miss cancer cells. Because of this difference, a fusion biopsy may reduce the number of repeat biopsies needed because of inconclusive results.

Cancer Grading

If cancer is found in the prostate biopsy, the amount of cancer and the aggressiveness of the tumor will be determined. The Gleason grade depends on how the tumor looks under the microscope. If the cancer looks a lot like normal prostate tissue, a grade of 1 is assigned. If the cancer looks very abnormal, it is given a grade of 5. Grades 2 through 4 have features in between these extremes. Most cancers are grade 3 or higher, and grades 1 and 2 are not often used. The higher the Gleason grade, the more likely the tumor is to behave aggressively (grow faster).

Since prostate cancers often have areas with different grades, a grade is assigned to the 2 areas that make up most of the cancer. These 2 grades are added to yield the Gleason Score (also called the Gleason Sum). The Gleason Score can be between 2 and 10, but most are at least a 6. The higher the Gleason Score, the more likely it is that the cancer will grow and spread quickly.

Grade Groups are a new way to grade prostate cancer to address some of the issues with the Gleason grading system.

As noted above, currently in practice the lowest Gleason Score that is given is a 6, despite the Gleason Scores ranging in theory from 2 to 10. This understandably leads some patients to think that their cancer on biopsy is in the middle of the score scale. This can compound their worry about their diagnosis and make them more likely to feel that they need to be treated right away.

Another problem with the Gleason grading system is that the Gleason Scores are often divided into only 3 groups (6, 7, and 8-10). This is not accurate, since Gleason Score 7 is made up of two grades (3+4=7 and 4+3=7), with the latter having a much worse prognosis. Similarly, Gleason Scores of 9 or 10 have a worse prognosis than Gleason Score 8.

To account for these differences, the Grade Groups range from 1 (most favorable) to 5 (least favorable):

• Grade Group 1 = Gleason 6 (or less)
• Grade Group 2 = Gleason 3+4=7
• Grade Group 3 = Gleason 4+3=7
• Grade Group 4 = Gleason 8
• Grade Group 5 = Gleason 9-10

Although eventually, the Grade Group system may replace the Gleason System, the two systems are currently reported side-by-side.

Cancer Staging

Once prostate cancer is diagnosed, the next step is to determine its stage. Staging is a system used to describe the size, aggressiveness, and spread of a cancer. A cancer’s stage helps to guide treatment and can help predict the chance of curing the cancer.

As with other tumors, cancer that involves only a small part of the prostate has a better chance of being treatable than cancer that has spread all through the gland. Likewise, tumors found only in the prostate are more successfully treated than those that have spread outside the prostate (metastasized). Finally, tumors that have spread to places far from the prostate such as to the lymph nodes or bone have the poorest results.

The system used for tumor staging is the TNM system, which stands for Tumor, Nodes and Metastasis. The “T” stage is found by DRE and other imaging tests such as ultrasound scan, CT scan, or MRI scan.

The imaging tests show if and where the cancer has spread, for example to lymph nodes or bone. Imaging tests for staging are often done for men with a Gleason grade of 7 or higher and a PSA higher than 10.

In addition, the PSA (prostate-specific antigen) level and the Gleason grade are used to gauge how aggressive the tumor is and what treatment options are available.

In general, lower-stage cancers are less aggressive and less likely to come back after treatment compared with higher-stage cancers. Stage I and II prostate cancer are referred to as localized prostate cancer, stage III as locally advanced prostate cancer, and stage IV as advanced or metastatic prostate cancer.

Risk Stratification

The initial management of men with newly diagnosed prostate cancer needs to incorporate a consideration of the prolonged natural history of the disease and the risk for progression to disseminated, potentially fatal disease.

The initial evaluation should include clinical staging based on a digital rectal examination by an experienced clinician to assess the extent of disease, the pretreatment serum prostate-specific antigen (PSA), the Gleason Score/Grade Group in the initial biopsy, and the number and extent of cancer involvement in the biopsy cores. This allows the stratification of men into risk categories according to the primary tumor, as defined by the National Comprehensive Cancer Network (NCCN).

National Comprehensive Cancer Network (NCCN) Risk Stratification

Treatment Options for Prostate Cancer

Typical treatment choices for prostate cancer include:

Surveillance

Active surveillance does not actively treat prostate cancer. It monitors the cancer growth with regular PSA tests, DREs, and periodic biopsies. A schedule for tests will be set with your provider. To help your provider do these biopsies, a multiparametric magnetic resonance imaging (mpMRI) exam might be done. With active surveillance, your doctor will know very quickly if the cancer grows. If that happens, then he/she will suggest next steps for you. At that point, radiation and surgery may be the best treatment options.

Active Surveillance is best if you have a small, slow growing (low-risk) cancer. It is good for men who do not have symptoms. If you want to avoid sexual, urinary or bowel side effects for as long as possible, this may be the treatment for you. Active surveillance allows men to maintain their quality of life longer without risking the success of treatment (if and when it’s needed). Action is taken only if the disease changes or grows. For many men, they never need more aggressive treatments.

Active surveillance is mainly used to delay or avoid aggressive therapy. On the other hand, this method may require you to have several biopsies over time to track cancer growth.

Watchful waiting is a less involved system of monitoring the cancer without treating it. It does not involve regular biopsies or other active surveillance tools. It is best for men with prostate cancer who do not want or cannot have therapy. It is also good for men who have other medical conditions that would interfere with more aggressive forms of treatment.

The main benefit of the watchful waiting treatment is that there are no treatment-related risks, complications or side effects. Also, it is low cost.

The risk of watchful waiting is that the cancer could grow and spread between follow-up visits. This makes it harder to treat over time.

Radiation Therapy

Radiation therapy (RT) uses high-energy rays to kill cancer cells. Two forms of RT are used to treat prostate cancer, external beam RT and brachytherapy. These are sometimes used together.

External beam RT, which is also often referred to as intensity-modulated RT, uses a machine that moves around you, directing X-rays at the pelvis. External beam RT is typically done in multiple daily treatments given over several weeks, depending on the specific technique used. Each treatment takes just a few minutes, and you can usually continue your normal activities during treatment. External beam RT is sometimes used in combination with androgen deprivation therapy (ADT).

Possible side effects of external beam RT include needing to run to the bathroom frequently to urinate, bladder pain, erectile dysfunction, and swelling and pain in the rectum (called proctitis). These symptoms are usually temporary.

In brachytherapy, a doctor places a radioactive source directly into the prostate gland. There are two types of brachytherapy, both of which are done under anesthesia.

• One type of brachytherapy, called low dose rate brachytherapy, involves placing rice-sized seeds, which emit radiation, into the prostate. The seeds gradually lose their radioactivity over time and are not removed. This is done as an outpatient procedure and does not require a hospital stay.
• High dose rate brachytherapy, which is used less frequently, involves temporarily implanting a radioactive source into the prostate gland, then removing it after one or two days. This treatment requires that you stay in the hospital for the one to two-day period and is usually combined with external beam RT.

Men who undergo brachytherapy usually develop inflammation and swelling of the prostate gland, which can lead to urinary urgency and frequency (needing to rush to the bathroom to urinate frequently), burning with urination, and occasionally, retention of urine (being unable to empty the bladder completely, which requires temporary use of a catheter). Some men also experience erectile dysfunction. Less commonly, some men have bowel urgency and frequency, rectal bleeding, and rectal ulcers. These problems usually resolve within a few weeks to months.

Surgery

There are three types of radical prostatectomy surgery:

Robotic-assisted laparoscopic radical prostatectomy (RALP) is the most common type of prostate cancer surgery done today. The surgeon is assisted with a robotic system that holds and guides the laparoscopic surgical tools and camera. It also allows the prostate to be removed through tiny ports placed in your belly. In experienced hands, RALP and retropubic prostatectomy (see below) have similar outcomes. There is also less blood loss with robotic surgery than other methods.

Retropubic open radical prostatectomy requires a cut (incision) in your lower belly and remove the prostate through this opening. The entire prostate gland is removed. Your surgeon can assess the prostate gland and surrounding tissue at the same time while reducing injury to nearby organs. There can be enough blood loss to need a transfusion.

Laparoscopic radical prostatectomy uses small cuts in the abdomen to remove the prostate with small tools and a camera. This surgery has mostly been replaced with robotic-assisted laparoscopic surgery.

After the prostate has been removed, the urinary tract and the bladder are reconstructed. A catheter is passed through the urethra into the bladder to drain the urine while the new connections heal. A suction drain may be left in the pelvic cavity after surgery. It is brought through the lower belly to drain fluid from the wound. It helps lower the risk of infection. The drain is usually removed before you are discharged from the hospital.

After surgery, your surgeon will review the final pathology report. Together you will make plans for the next steps.

The main benefit of a radical prostatectomy is the prostate with cancer is removed. This is true as long as the cancer hasn’t spread outside the prostate. Surgery also helps the healthcare provider know if you need more treatment.

The goal of surgery is to get a PSA value of less than 0.1 ng/mL for 10 years. Surgery is often a good choice if prostate cancer has not spread beyond the prostate.

Surgery always comes with risks. Some complications from surgery can happen early and some later. Bleeding or infection can happen with any major operation, so you will be monitored to prevent or manage these problems.

Not everyone has the same side effects for the same amount of time. With surgery (and with radiation therapy), there are two main side effects to consider: erectile dysfunction (ED) and urinary incontinence (a loss of urine control). For some men, surgery can relieve pre-existing urinary obstruction. Most men with these side effects find ways to manage them over time.

Most men have some form of erectile dysfunction after prostate surgery. Erectile dysfunction is the inability of a man to have an erection long enough for satisfying sexual activity. Nerves involved in the erection process surround the prostate gland, and they can be affected by surgery. They can also be affected by radiation treatment. These nerve bundles help control blood flow to the penis. The length of time ED lasts after treatment depends on many things, including how firm your erections are before treatment. Sometimes, it may take one year or longer to recover erectile function. In the meantime, your doctor may have ED treatment options for you. If it’s possible, nerve-sparing surgery may help prevent long-term damage. Older men have a higher chance of permanent ED after this surgery.

It may surprise you to know that men are still able to have an orgasm (climax), even after a radical prostatectomy. An erection is not needed to climax. There will be very little if any, fluid with an orgasm. In addition, you can no longer cause a pregnancy after surgery. This is because the prostate, seminal vesicles, and connections to the testicle were removed and the vas deferens was divided during surgery. Planning for fertility preservation in advance of surgery is an option for men who want to have children.

It is important to know that sexual desire is not lost with this surgery or radiation treatment. The exception to this is if hormones are also given as part of treatment, (usually given temporarily with radiation therapy).

Incontinence is the inability to control your urine. After prostate cancer surgery, you may experience one or more type of Incontinence.

• Stress Incontinence — is urine leakage when coughing, laughing, sneezing or exercising. It is the most common type of urine control problem after radical prostatectomy.
• Overactive Bladder (Urge Incontinence) — is the sudden need to go to the bathroom even when the bladder is not full because the bladder is overly sensitive. This type of incontinence is the most common form after radiation treatment.
• Mixed Incontinence — is a combination of stress and urge incontinence with symptoms from both types.
• Continuous Incontinence — is the inability to control urine at any time. It is not very common.

Cryotherapy and Other Ablative Techniques

Ablation techniques, including cryotherapy and high-intensity, focused ultrasound (HIFU), have been used to destroy tissue, either by freezing or by generating local thermal energy and thereby treat prostate cancer. These ablation techniques can be applied to the entire prostate gland or to only the part of the gland thought to be involved with cancer.

Cryotherapy is a treatment modality for localized prostate cancer in which freezing is used to destroy tumor cells. Potential advantages of cryoablation compared with other therapeutic options in men with localized prostate cancer include:

• The ability to destroy cancer cells using a relatively noninvasive procedure. Cryotherapy is associated with minimal blood loss and pain, is much better tolerated than an open radical prostatectomy, and has a more rapid posttreatment convalescence. These differences may be less pronounced compared with minimally invasive (robotic or laparoscopic) prostatectomy.
• Cryotherapy can be performed under spinal rather than general anesthesia and therefore can be offered to men who are not candidates for surgery because of advanced age or comorbidities.
• Cryotherapy can be used to treat men with localized disease or locally recurrent cancer following initial RT. Cryoablation can be performed more than once; if necessary, it can be followed by either RT or radical prostatectomy.

High-intensity focused ultrasound (HIFU) uses sonic waves to create thermal energy that destroys the target tissue within the prostate. Various devices are available for HIFU in different areas (i.e., Ablatherm, Sonablate). HIFU has not been compared with standard treatment approaches in randomized trials, nor is it included in guidelines for the initial management of men with prostate cancer. The FDA has approved prostate HIFU as a minimally invasive treatment approach to ablate prostate tissue.

Systemic Therapy

Hormonal therapy is also known as androgen deprivation therapy (ADT). It uses drugs to block or lower testosterone and other male sex hormones that fuel cancer. ADT essentially starves prostate cancer cells of testosterone. ADT is used to slow cancer growth in cancers that are advanced or have come back after initial local aggressive therapy. It is also used for a short time during and after radiation therapy.

Hormone therapy is done surgically or with medication:

• Surgery — Removes the testicles and glands that produce testosterone with a procedure called an orchiectomy.
• Medication — There are a variety of medications used for ADT. There are two types that are used at first. One is the injection of luteinizing hormone-releasing hormone (LH-RH) inhibitors. These are also called either agonists or antagonists. They suppress the body’s natural ability to turn on testosterone production. A second type (which is often given with the first type) are called non-steroidal anti-androgens. These pills block testosterone from working.
  These therapies have been used for many years and are often offered as the first option for men who can’t have or don’t want other treatments. Hormone therapy usually works for a while (maybe for years) until the cancer “learns” how to bypass this treatment.There are new medications available in recent years that may be used after other hormone therapy fails. This condition is called “castration-resistant prostate cancer” (CRPC).To block the production of androgens in CRPC patients, there are a few options. The drug Abiraterone (Zytiga), given with prednisone, is one option that blocks an enzyme called CYP17, to stop these cells from making androgens. Another option is a drug, enzalutamide (Xtandi) that blocks the testosterone from working in a different way. This medication blocks signals in cells that tell it to grow and divide. Like other hormone therapies, these options also only work for a while. When they stop working, chemotherapy may be an option.

Hormone therapy has been linked to heart disease, diabetes and the loss of bone. You should discuss these risks with your doctor before you begin this treatment for prostate cancer.

Hot flashes and fatigue are also short-term side effects of hormone treatment. The same is true for the loss of sexual drive.

Chemotherapy uses drugs to destroy cancer cells anywhere in the body. It is used for advanced stages of prostate cancer. It is also used when cancer has metastasized (spread) into other organs or tissue. The drugs circulate in the bloodstream. Because they kill any rapidly growing cell, they attack both cancerous cells and non-cancerous ones. Dose and frequency are carefully controlled to reduce the side effects this may cause. Often, chemotherapy is used with other treatments. It is not the main treatment for prostate cancer patients.

Many chemotherapy drugs are given intravenously (with a needle in a vein). Others are taken by mouth. They are given in the healthcare provider’s office or at home. You generally do not need to stay in the hospital for chemotherapy. They are often given once per month for several months.

Over the last 10 years, chemotherapy has helped many patients with castrate-resistant prostate cancer (CRPC). Recently, chemotherapy has also been found to help patients with advanced prostate cancer when given at the same time as standard hormone therapy. Yet, chemotherapy may only work for a while.

The side effects from chemotherapy should be considered. Side effects depend on the drug, the dose and how long the treatment lasts. The most common side effects are fatigue (feeling very tired), nausea, vomiting, diarrhea and hair loss. A change in your sense of taste and touch is also possible. There is an increased risk of infections and anemia because of lower blood cell counts. Most of these side effects can be managed and lessen once treatment ends.

Immunotherapy stimulates your body’s immune system to find and attack cancer cells. There are several approaches used in immunotherapy. Most of these are now in clinical trials and have not yet been approved for routine use.

Provenge is one type of immunotherapy that is already FDA approved. It has been shown to help slow cancer growth in men with advanced prostate cancer. For this treatment, the medical team must remove immature immune cells from the man with advanced prostate cancer. Then the cells are re-engineered to recognize and attack prostate cancer cells and put back into the body.

While cancer doctors are excited about the potential of immune therapies, clinical trials have not yet shown clear successful results. So far, most immunotherapy approaches have only mild to moderate side effects.

Risk-Stratified Approach to Treatment of Prostate Cancer

The following treatment recommendations based on risk stratification are consistent with guidelines from the American Urological Association (AUA), American Society for Radiation Oncology (ASTRO), Society of Urologic Oncology (SUO), which have been largely endorsed by the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN).

Risk-Stratified Approach to Treatment of Prostate Cancer