How Prostate Cancer Is Treated

The treatment options for prostate cancer can vary based on many factors, including the aggressiveness of the tumor, the stage of the disease, personal preferences, and more. Curative options may include surgery or radiation therapy. With less aggressive tumors, watchful waiting (active surveillance) with treatment begun only if the cancer progresses may be an option. There are also a number of different therapies that can be used to control the growth of these cancers, including hormone therapies, chemotherapy, and newer treatments such as immunotherapy. In addition, many alternative treatments are being evaluated in clinical trials.

Understanding Your Options

Many prostate cancers are non-aggressive, and if, left alone, would not pose a problem over the long term. With these tumors, observing the tumor (active surveillance) and treating the tumor only if it shows signs of progressing may be an option.

With early prostate cancers that show signs of being aggressive, and in people who are able to tolerate treatments such as surgery, the aim of therapy is usually a cure. Surgery and radiation are considered standard treatment options, though alternatives—such as proton therapy, cryoablation, and high intensity focused ultrasound—are being evaluated.

With more advanced prostate cancers (including metastatic tumors), or in those who are unable to tolerate curative treatments, the aim is usually to control the growth of the cancer for as long as possible. Systemic treatments may include hormonal therapies, chemotherapy, immunotherapy, or a clinical trial. Keep in mind that, unlike many cancers, advanced prostate cancer can often be controlled for a long period of time with these treatments (often decades).

Knowing whether your cancer is low-grade, intermittent-grade, or high-grade is critical in making the best choices about treatment. Many men are more likely to die with prostate cancer than from prostate cancer, and in many cases, the goal is to treat the disease while preserving the best quality of life.

Active Surveillance

Active surveillance is often referred to as watchful waiting, though some use these terms to describe slightly different approaches. 

With active surveillance, a man chooses not to have his cancer actively treated at the current time. PSA levels are checked at specific intervals (for example, every six months), with a digital rectal exam performed yearly, and second and third biopsies done six to 12 months and two to five years after beginning surveillance. (The timing can vary depending on characteristics of the cancer.) If at any time the cancer appears to progress, active treatment is then started.

Active surveillance is most often used with early-stage, slow-growing tumors, for which the side effects of treatment (such as erectile dysfunction and incontinence) outweigh the potential benefits of treatment. It is used most often with Gleason 6 tumors, but may also be used for men with tumors that have higher Gleason scores who may decide the side effects of treatment outweigh benefits for personal reasons, or due to other health conditions.

It's extremely important to note that active surveillance is viewed as a standard treatment method by many of the cancer organizations. It's thought that around 25 percent of men who are "treated" with active surveillance will require active treatment at some point in the future, but waiting to see if a person falls in that category does not carry the risk of the disease suddenly metastasizing and causing death.

When a physician makes a distinction between this and watchful waiting, he or she is typically using the latter term to refer to a similar approach with no or less frequent testing. This may be an option for treatment for those who are expected to live less than five years, for example. In this case, follow-up tests are not usually done unless symptoms develop, and if this occurs, treatment may be initiated at that time. There are a number of other reasons why this option may be chosen as well.

Surgery

Both surgery and radiation are considered "curative" therapies for prostate cancer. Other surgical procedures may be used for other reasons, such as symptom control.

Prostatectomy

In a traditional prostatectomy, an incision is made midline in the abdomen, between the belly button (umbilicus) and pubic bone. A surgeon uses this access point to manually remove the prostate gland as well as surrounding tissues, such as the seminal vesicles. In a radical retropubic prostatectomy, pelvic lymph nodes may be removed as well.

Surgeons can also achieve this treatment goal with what's known as a robotic prostatectomy. Instruments are inserted into several small incisions in the lower abdomen, which are moved by a robot controlled by a surgeon rather than the surgeon's hands themselves.

This is less invasive than the manual procedure, gives the surgeon better visibility, and may have several other advantages, including less of a risk of blood loss, shorter recovery time, and faster removal of the catheter (one is required for either procedure).

Robotic prostatectomy is a highly specialized procedure, and there is a steep learning curve in learning the technique. For those who choose this option, you must find a surgeon specially trained to perform the procedure and has a significant level of experience in doing so.

The risk of sexual side effects as well as incontinence is similar among the above options.

After the surgery is performed, the prostate tissue is sent to a pathologist to determine if all of the tumor was removed. With prostate cancer, this can be challenging. The rectum and bladder lie within millimeters of the prostate gland and cannot be removed with surgery. This means that sometimes a surgeon will cut through a tumor rather than around the tumor, leaving prostate cancer cells behind. 

When cancer cells are left behind (when surgical margins are positive) the risk of the cancer recurring is around 50 percent. Further treatment will depend upon the aggressiveness of the tumor but may include careful monitoring, radiation treatment to the prostate fossa, hormonal therapy, and/or chemotherapy.

Transurethral Resection of the Prostate (TURP)

In this procedure, a resectoscope is inserted in the urethra, and an electrically activated wire loop is used to burn away prostate tissue.

A TURP is not done as a curative treatment for prostate cancer. It is sometimes recommended as a palliative procedure (to help symptoms but not cure the disease) for stage 4 cases. It may also be done to treat BPH (benign prostatic hypertrophy) with symptoms that persist despite treatment. 

Orchiectomy

An orchiectomy is the surgical removal of both of the testicles. Since the testicles produce 95 percent of the testosterone in the body, this procedure greatly reduces the amount of the testosterone in the body. (Just as normal prostate cells are driven by testosterone, the hormone acts as the fuel that drives the growth of prostate cancer cells.)

Post-Operative Care

After a prostatectomy (either manual or robotic) men will have a Foley catheter in place. The catheter will usually be left in place for at least 24 hours but may need to remain in place for up to two weeks while swelling and inflammation resolves. During the first few days, it's normal to pass some blood or small clots. Your surgeon will instruct you in good incision care following discharge, which can reduce your risk of infection or other complications.

In general, men can return to their normal activities within four weeks of surgery but may be able to do so in as little as a week following outpatient procedures.

As with any surgical procedure, there is a risk of side effects and complications following a prostatectomy. Possible complications, which may be temporary, include the following. Most men do not experience all of these:

  • Difficulty urinating
  • Urinary incontinence, though there are a number of treatments that can help this
  • Bleeding
  • Infection
  • Erectile dysfunction
  • Retrograde ejaculation (ejaculation into the bladder rather than out of the penis)
  • Surgical injury to structures surrounding the prostate
  • TURP syndrome, an uncommon but potentially serious complication of TURP surgery that results from a serious drop in serum sodium due to flushing of fluids during the procedure 
  • change in penis size (With a radical prostatectomy, roughly 20 percent of men will note a change in size or girth of the penis of 15 percent or more.)

Radiation Therapy

Radiation works by using high energy rays to damage and kill cancer cells and may be used as the primary treatment for prostate cancer as an alternative to surgery (curative therapy); after surgery as an adjuvant therapy to treat any remaining cancer cells that remain; or as a palliative treatment to improve symptoms, but not to cure the cancer. Radiation can be very helpful to treat areas of bone metastases due to the disease.

Radiation therapy may be given externally or internally, and oftentimes the two methods are used together. 

External Beam Radiation Therapy

In this procedure, you are positioned on an exam table and radiation is delivered through the outside of the body and focused on the prostate gland and surrounding tissue. A gel called spaceOAR may be placed between the rectum and prostate to reduce the risk of rectal burns, but techniques for delivering radiation have improved remarkably in recent years and cause much less damage to surrounding normal tissues than in the past. 

Brachytherapy (Radioactive Seed Placement)

Internal radiation therapy, also known as brachytherapy, radioactive seed placement, or simply "seed implant," may be used as the primary treatment for prostate cancer or in combination with external radiation therapy. In this procedure, small seeds or pellets of radiation are implanted in a tumor. Radioactive seeds may be either temporary or permanent. 

Traditional brachytherapy is used mostly for low-grade or slow-growing tumors. For men with low to moderate risk prostate cancer, low-dose brachytherapy may be used alone as the primary treatment for prostate cancer according to 2017 joint guidelines of the American Society of Clinical Oncology and Cancer Care Ontario.

High-dose brachytherapy (HDR) is often used for more advanced tumors. In HDR, a catheter is placed into the prostate between the scrotum and anus, and a needle containing the rice-sized radioactive seeds is then placed inside the catheter and kept in place for five to fifteen minutes. This is typically repeated three times over two days.

When used as a curative therapy, radioactive seed implantation results in higher cure rates than standard beam radiation.  In combination, these treatments appear to lower the risk of relapse at nine years post-treatment by 20 percent, relative to men who have external beam radiation alone. It's thought that for men with intermediate- or high-risk prostate cancer who choose external beam radiation therapy, either a low-dose or high-dose brachytherapy boost should be offered.

Brachytherapy is not as effective in men who have an enlarged prostate gland.

Side Effects

Side effects of both forms of radiation may include painful urination, frequency, and urgency; incontinence; loose stools; bleeding or pain when passing stools. These symptoms are usually mild to moderate and improve over time. Erectile dysfunction may occur but is more often seen in older men with this pre-existing issue. When it occurs in others, it tends to resolve quickly and completely after treatment.

With external radiation, redness, a rash, and blisters may form on the skin overlying the prostate.

When radioactive seeds are left in place in brachytherapy, cautions are needed as others who are nearby may be affected by the radiation. Men are usually instructed to stay away from pregnant women or small children, sometimes for a significant period of time. It's also important to note that the radiation may be strong enough to be picked up at airport screening.

Other Local Therapies

In addition to surgery and radiation therapy, there are a few other local treatments that may be used with a curative intent.

Proton Beam Therapy

Proton beam therapy is similar to conventional radiation therapy in that it uses high energy to destroy cancer cells. However, the rays—which are composed of accelerated protons, or positive particles—pass through tissue directly to a tumor and stop, as opposed to continuing on past the prostate gland where they can damage normal tissue (as is the case with regular radiation).

Proton therapy appears to about as effective as traditional radiation but is thought to cause less damage to normal, healthy cells.

Proton therapy is relatively new compared with some other treatments, and its role as primary therapy (monotherapy) for prostate cancer is promising but still unclear. 

Cryosurgery

Cryosurgery or cryoablation is a technique in which argon and helium are used to freeze the prostate. It is used in the operating room while men are under anesthesia.

Used less than other treatments, cryotherapy can only be used on tumors that are contained within the prostate gland and only present in one location. It may also be used after failed radiation treatment.

The positive benefits may include a more rapid recovery and shorter hospital stay than surgery (prostatectomy), although the technique carries a greater risk of erectile dysfunction.

High-Intensity Focused Ultrasound (HIFU)

High-intensity focused ultrasound (HIFU) uses ultrasound to generate heat and kill cancer cells. It's thought that HIFU may be less effective than other common treatments, but surgery or radiation therapy may be subsequently used if it is not successful.

Hormone Therapy

Medications can be used to reduce the amount of testosterone present in the body (just like orchiectomy) or interfere with the ability of testosterone to act on prostate cancer cells. Hormone therapy (androgen deprivation therapy) does not cure prostate cancer but is a mainstay for controlling its growth—sometimes for an extended period of time.

Hormone therapy can be used for men who would otherwise not tolerate other treatments. It can also be used before radiation, to reduce the size of a prostate cancer and make it easier to treat (neoadjuvant therapy), or after, to help "clean up" any remaining cancer cells to reduce the risk of recurrence or relapse (adjuvant therapy). Finally, it can be used for men who have prostate cancers that have recurred after primary treatment or who have cancers that have metastasized (spread) to other regions of the body.

LH-RH Therapy

Luteinizing releasing hormone (LH-RH) analogues or agonists block the signal that tells the testicles to make testosterone, reducing overall production. These drugs are a medical version of an orchiectomy, and the treatment is sometimes referred to as medical castration. In contrast to orchiectomy, however, treatment is reversible.

Drugs in this category include:

  • Lupron (leuprolide)
  • Zoladex (gosrelin)
  • Trelstar (triptorelin)
  • Vantas (histrelin)

When LH-RH agonists are first used, they often cause an increase in testosterone levels. To counteract this effect, and anti-androgen medication is often used during the first weeks of treatment.

LH-RH antagonists also reduce the production of testosterone by the testicles but do so more rapidly than LH-RH agonists.

Drugs in this category include:

  • Firmagon (degarelix)

CYP17 Inhibitors

Unlike LH-RH agonists and antagonists, CYP17 inhibitors interfere with the production of testosterone by the adrenal glands (small endocrine glands that sit atop the kidneys). They do so by blocking the enzyme CYP17, which is needed in the reaction that produces androgens.

There is one drug in this category that is approved for use in the United States.

  • Zytiga (abiraterone)

There are others (such as orteronel, galeterone, V-464) that are in clinical trials and more in development. Ketoconazole, an antifungal with CYP17 inhibitory properties, is sometimes used off-label for prostate cancer.

Zytiga (abiraterone) is used along with the medications discussed above to block the production of all testosterone in the body and is used primarily in advanced/high-risk and metastatic prostate cancer. Side effects are usually mild and include problems with potassium levels in the blood. It is sometimes given along with prednisone to reduce these problems, but corticosteroids like prednisone. The medication also enhances the effect of some cholesterol-lowering medications.

Anti-Androgen Therapy

Some anti-androgen medications bind to the androgen receptor on prostate cancer cells so that testosterone cannot, preventing cell division and growth.

These include:

  • Eulexin (flutamide)
  • Casodex (bicalutamide)
  • Nilandron (nilutamide)

Others block the signal from the receptor to the nucleus of the cell, achieving the same result.

These include:

  • Xtandi (enzalutamide)
  • Earleada (apalutamide)

Benign Prostatic Hypertrophy (BPH) Medications

The medications Avodart (dutasteride) and Proscar (finasteride) block dihydrotestosterone.

Avodart or Proscar may be used in prostate cancer:

  • For men with Gleason 6 tumors to suppress tumors or cause them to regress
  • Along with Lupron or Casodex to make these drugs work better
  • To help maintain men on active surveillance and reduce the risk they will need surgery or radiation

When used for men who do not have prostate cancer, these drugs appear to reduce the risk of developing the disease, though there is an increased incidence of high-grade cases in those who do end up diagnosed.

Side Effects and Considerations

Most of the side effects related to hormone therapy are secondary to the reduction of testosterone in the body. It's important to note that one's physical appearance does not change due to these treatments, nor does the voice change. Side effects may include:

  • Hot flashes
  • Erectile dysfunction
  • Decreased sex drive
  • Breast enlargement (gynecomastia)
  • Fatigue
  • Weight gain
  • Reduced muscle strength
  • Reduced bone density (osteopenia and osteoporosis)

To reduce these side effects, hormone therapy may sometimes be used intermittently, with breaks from the drug to improve quality of life.

Since testosterone "feeds" prostate cancer, some people have wondered whether men with prostate cancer can take testosterone; replacement hormone can help low sex drive, erection issues, fatigue, and more. Many people would quickly say "no," but there are some situations in which this is possible:

  • With low-grade or benign tumors (the types that would never spread such as Gleason 6 tumors)
  • For men who have had surgery or radiation therapy and are felt to be cured, after a waiting period of two to five years
  • For men who have relapsed after surgery or radiation who are receiving intermittent Lupron, though experts' opinions are divided
  • For men with prostate cancer who have very severe weakness or muscle loss; the risks of not treating with testosterone may outweigh the risk of the cancer growing.

Chemotherapy

Chemotherapy drugs work by killing rapidly dividing cells such as cancer cells, although normal cells can also be affected. Chemotherapy may both extend life and reduce symptoms for men living with prostate cancer. That said, it cannot cure the disease.

Chemotherapy drugs used for prostate cancer include:

  • Taxotere (docetaxel), usually the first-choice chemotherapy drug
  • Jevtana (cabazitaxel), an enhanced form of chemotherapy that can be used in men who become resistant to Taxotere
  • Novantrone (mitoxantrone)
  • Emcyt (estramustine)

Chemotherapy is usually used for prostate cancers that have spread beyond the prostate gland and are no longer responding to the hormonal therapy drugs, but this is changing.

2015 study published in The New England Journal of Medicine found that men who had hormone-sensitive tumors and were treated with Taxotere and Lupron survived much longer than men who were treated with Lupron alone. Due to these findings, chemotherapy is now recommended earlier, prior to the development of hormonal resistance for men with significant metastatic disease.

Side Effects

Some of the common side effects of chemotherapy include:

  • Hair loss
  • Bone marrow suppression: This can include a low white blood cell count (chemotherapy-induced neutropenia), a low red blood cell count (chemotherapy-induced anemia), and a low platelet count (thrombocytopenia).
  • Peripheral neuropathy: Numbness, tingling, and pain in the hands and feet are common, especially with drugs such as Taxotere and Jevtana. While most of the side effects of chemotherapy resolve shortly after treatments are completed, peripheral neuropathy may persist.
  • Nausea and vomiting: Medications can now control these symptoms so that many men experience little or no nausea.

Immunotherapy

Biological therapy, also called immunotherapy, uses your body's immune system to fight cancer cells. One type, called Provenge (sipuleucel-T), has been developed to treat advanced, recurrent prostate cancer.

Provenge is a therapeutic cancer vaccine that is approved for men with prostate cancer that have developed resistance to hormone therapies and have either no symptoms or only mild symptoms of the disease. Like vaccines that stimulate the body to fight off bacteria or viruses, Provenge stimulates a man's body to fight off cancer cells. It works by enhancing a specific type of immune cell known as T regulatory cells (Tregs) that act like the bloodhounds of the immune system. T regulatory cells recognize an invader such as a cancer cell and then send signals to other cells (killer T cells) in the immune system to destroy the cancer.

With this therapy, a man's blood is first withdrawn (in a procedure called plasmapheresis that is similar to dialysis) and his T regulatory cells are isolated. The Tregs are then exposed to prostatic acid phosphatase, a molecule found on the surface of prostate cells, training the Tregs to recognize these cancer cells as invaders. The cells are injected back into the man to do their job. 

Monitoring progress can be challenging for men with Provenge, as PSA levels and the size and extent of tumors does not change. Yet, this can extend survival by several months with minimal side effects. It has more benefit when the medication is started sooner, as the effect is cumulative over time.

Combining radiation therapy with immunotherapy appears to make the treatment work better via a process called the abscopal effect. The dying cells from radiation help the immune cells identify tumor-specific molecules so they can hunt them down in other areas of the body.

Clinical Trials

There are a number of different clinical trials in progress looking for newer and better ways to treat prostate cancer (or ways that have fewer side effects). Drugs that are being studied include other immunotherapy drugs as well as targeted therapies, treatments that target specific genetic abnormalities in cancer cells or the growth pathway of cancer cells. PARP inhibitors are medications that have been evaluated for people with breast cancer and may be helpful for men with prostate cancer who have BRCA gene mutations.

Treatment of Metastases

Prostate cancer can spread to bones and other regions of the body. General treatments for prostate cancer can also address metastases, but specific treatments are also used at times.

Bone metastases can be treated in a number of different ways. Treatment can reduce pain and also reduce the risk of complications of bone metastases such as fractures and spinal cord compression. Options include:

  • Radiation therapy
  • Radiopharmaceuticals: Metastron (strontium-89), Quadramet (samarium-153), and radium-223 can be injected and delivers radiation directly to bones. These treatments are particularly helpful if bone metastases are widespread or present in different areas of the body.
  • Bone-modifying drugs: Bone-modifying drugs work by changing the microenvironment of bones and can be used to both treat and prevent bone metastases. Agents include the bisphosphonate drug Zometa (zoledronic acid) and Xgeva or Prolia (denosumab). 

Liver metastases may also sometimes be treated specifically. Liver metastases can be very serious with prostate cancer and are most often treated with general treatments for metastatic cancer. For some men, however, SIR-Spheres to treat liver metastases may be an option when other treatments are not controlling the disease in the liver.

Complementary Treatments

At present, there are no alternative treatments that can cure prostate cancer or extend life, but studies looking at issues ranging from diet to medications not traditionally used for prostate cancer indicate that such options may play a complementary role in the future. 

Diet

A healthy, balanced diet is necessary for healing from the treatments used for prostate cancer. A 2016 study suggested that foods high in lycopene, such as tomato sauces, may have some benefit for men with high-risk prostate cancer. There has been some thought that a diet high in meat and animal fat may be detrimental, but this is not well understood at this time.

Vitamins

There is some evidence that vitamins, such as taking a multivitamin, zinc, or calcium, may increase the mortality from prostate cancer. While it's too soon to know the significance of vitamins with prostate cancer, some vitamin and mineral supplements may interfere with treatment. It's important to talk to your doctor not only about your prescription medications, but any over-the-counter medications, vitamins, or dietary supplements you wish to take.

Metformin

It appears that men who have diabetes and prostate cancer live longer when treated with metformin than with other diabetes medications, but the drug is also being studied for its possible role in treating some cancers themselves. Its role in the treatment of prostate cancer is still uncertain, however.

Statins

Statins are the category of cholesterol-lowering drugs, such as Lipitor (atorvastatin), that many people are familiar with. In studies to date, it appears that men treated with statins have a reduced risk of death and a higher cure rate from prostate cancer.

Aspirin

Studies have looked at the role that aspirin may have in the survival from many cancers. A large 2014 study published in the Journal of Clinical Oncology found that low-dose aspirin was associated with a lower risk of dying from prostate cancer, but only for those who had high-risk tumors. The benefits of treatment need to be weighed against the possible risks (such as bleeding ulcers), and it's important to talk to your doctor if you are considering using aspirin.

Foregoing Treatment

There are people who may choose to forego treatment, even if they are a candidate for it. For some men, a short life expectancy or other serious medical problems may result in this choice. In this case, a man may feel that the risks or side effects of treatments outweigh their potential benefits. 

Since what will happen if prostate cancer goes untreated will vary depending on many factors, it's important to clearly ask your doctor about your case. Understanding the possible course of your cancer and how likely progression is to occur can help you make an educated decision about your care. Choosing to forego treatment is certainly reasonable in the right circumstances but requires a careful and thoughtful discussion with your doctor and family.

Making Decisions

There are a number of different doctors that treat prostate cancer, including urologists, radiation oncologists, medical oncologists, and primary care physicians such as internists and family physicians. You may get differing opinions as to the best treatment for you depending on a practitioner's clinical focus. By learning about your disease and consulting more than one physician, you can weigh the different options for yourself and become an active voice in your care.

Many people find it helpful to get a second opinion at one of the National Cancer Institute-designated cancer centers. These centers are not only known for their top-notch specialists in the field of cancer but often offer more clinical trials than community hospitals. Some specialists may design a plan of treatment that can then be undertaken by your community physician.

Sources:

American Society of Clinical Oncology. Prostate Cancer: Treatment Options. Updated 03/2018.

Arimura, T., Kondo, N., Matsukawa, K. et al. Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study. Journal of Clinical Oncology. 2018. 10(14):116.

Chin, J., Rumble, R., Kollmeier, M. et al. Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guidelines. Journal of Clinical Oncology. 2017. 35(15):1737-1743.

Cooperberg, M. Long-Term Active Surveillance for Prostate Cancer: Answers and Questions. Journal of Clinical Oncology. 2015. 33(3):238-240.

Frank, S., Pugh, T., Blanchard, P. et al. Prospective Phase 2 Trial of Permanent Seed Implantation Prostate Brachytherapy for Intermediate-Risk Localized Prostate Cancer: Efficacy, Toxicity, and Quality of Life Outcomes. International Journal of Radiation Oncology, Biology, and Physics. 2018. 100(2):374-382.

Jacobs, E., Newton, C., Stevens, V. et al. Daily Aspirin Use and Prostate Cancer-Specific Mortality in a Large Cohort of Men With Nonmetastatic Prostate Cancer. Journal of Clinical Oncology. 2014. 32(33):3716-22.

Sweeney, C., Chen, Y., Carducci, M. et al. Chemothormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. The New England Journal of Medicine. 2015. 373:737-746.