Treatment & Management of Prostate Cancer
Medically reviewed by Dr. C.H. Weaver M.D. 6/2020
Choice of prostate cancer treatment is influenced by several factors. The treatment selected may be influenced by the patient’s age, concurrent health problems, life expectancy, the genomic profile and characteristics of the individual’s cancer, the patient’s goals of treatment, and the bias of the treating physician. Treatment options include hormone therapy, surgery, radiation, newer precision cancer medicines, combinations of therapy and “watchful waiting.” It is important to obtain as much information as possible about the results of each treatment and obtain more than one opinion, especially when deciding on surgery versus radiation therapy.
Several different doctors treat prostate cancer and may be involved with the diagnosis and management of prostate cancer including an urologist, radiation oncologist and a medical oncologist. Urologists are surgeons who specialize in treatment of disorders of the male genital tract, including prostate cancer. Urologists play an important role in the diagnosis and treatment of prostate cancer. Radiation oncologists use various forms of radiation to treat prostate cancer and medical oncologists are often involved when chemotherapy is required.
Treatment of Prostate Cancer
Surgery is used to diagnose, stage, and treat prostate cancer. Surgical removal of the prostate is considered a local treatment and is very effective treatment if the cancer has not spread beyond the prostate.
In radiation therapy, high-energy X-rays are used to kill prostate cancer cells. In early-stage prostate cancer, radiation can be used instead of surgery, or it may be used after surgery to destroy any cancer cells that may remain in the area. In advanced stages of prostate cancer, it may be given to relieve pain or other problems.
Testosterone is a male hormone produced mainly by the testicles. Many organs in the body are composed of cells that respond to or are regulated by exposure to testosterone. Cells in the prostate have testosterone receptors and when exposed to testosterone, are stimulated to grow. When cells that have testosterone receptors become cancerous, the growth of these cancer cells can be increased by exposure to testosterone. The basis of hormone therapy as a treatment for prostate cancer is to block or prevent the cancer cells from being exposed to testosterone.
Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment.
Targeted Therapy - Precision Cancer Medicines
Targeted therapies are designed to treat only the cancer cells and minimize damage to normal, healthy cells. Treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes.
Biological or Immunotherapy Therapy
Biological therapy is referred to by many terms, including immunologic therapy, immunotherapy, or biotherapy. Biological therapy is a type of treatment that uses the body’s immune system to facilitate the killing of cancer cells. Types of biological therapy include interferon, interleukin, monoclonal antibodies, colony stimulating factors (cytokines), and vaccines. Biologic therapies are being developed for the treatment of prostate cancer. Sipuleucel-T(Provenge®) is an immunotherapy that prompts the body’s immune system to respond against the cancer, and was recently approved by the FDA.
Active Surveillance & Watchful Waiting
Some physicians and patients choose a strategy of delaying any treatment of prostate cancer until symptoms from the cancer appear. Because treatment with radiation or surgery may be associated with side effects, in addition to inconvenience, electing not to receive immediate treatment may be appropriate for selected patients especially those with other health concerns or a shorter life expectancy.
Watchful waiting is based on the premise that some patients will not benefit from definitive treatment of the primary prostate cancer. The decision is to forgo definitive treatment and to instead provide treatment to relieve symptoms of local or metastatic progression if and when it occurs. In contrast to watchful waiting, a program of active surveillance is based on the premise that some, but not all, patients may benefit from treatment of their primary prostate cancer. A program of active surveillance is designed to provide definitive treatment for men with localized cancers that are likely to progress and to reduce the risk of treatment-related complications for men with cancers that are not likely to progress. Clinical studies suggest that individuals with lower risk cancers could be candidates for this treatment strategy because they have a low risk for clinical progression of their cancer within the first 10 to 15 years after the diagnosis. Thus, this treatment strategy may be best suited for men with a shorter life expectancy.
Role of Surgery in Prostate Cancer
Nearly all patients with prostate cancer will have some kind of surgery. Surgery may be used to perform a biopsy in order to obtain a specimen for determining an accurate diagnosis, provide local treatment of the cancer, and obtain other information to help determine whether additional treatment is necessary. Surgical techniques continue to improve, and surgeries are now less invasive and often performed on an outpatient basis.
A surgeon who specializes in treatment of disorders of the male genital tract, including prostate cancer, is known as a urologist. A urologist plays an important role in the diagnosis and treatment of prostate cancer. Individuals with early-stage prostate cancer have several treatment options including surgery, which may be used alone or in combination with other therapies.
If laboratory tests or physical examination results suggest that prostate cancer may be present, you will need to have a prostate biopsy. A biopsy is the only way to know for sure whether an individual has cancer. During a biopsy, a needle is used to remove several small pieces of prostate tissue through the rectum. These pieces of prostate tissue are examined under the microscope to determine whether cancer cells are present. If cancer cells are present, an assessment of how aggressive or abnormal the cancer appears is performed.
Radical Prostatectomy and Lymph Node Dissection
Surgery is a common treatment of Stage I, II, and sometimes Stage III cancer of the prostate. The operation used to remove the prostate cancer is called a radical prostatectomy. During a radical prostatectomy, the entire prostate gland with the cancer and a rim of normal tissue around it is removed. With a radical prostatectomy, a portion of the urethra, or tube that empties the bladder through the penis, is removed and the cut ends are re-attached. To help with the healing of the urethra, the patient will go home with a catheter into the bladder for a couple of weeks.
Radical prostatectomy is most effective if the staging evaluation shows that the cancer has not spread outside the prostate. This is because surgery cannot remove cancer that has already spread away from the prostate gland. Some patients will have small amounts of cancer that have spread outside the prostate into the pelvic lymph nodes or other distant locations. In general, the higher the stage, the more likely the cancer will have spread away from the prostate.
Before a prostatectomy is performed, the urologist may perform surgery to take out lymph nodes to see if they contain cancer. This is called a pelvic lymph node dissection. If the lymph nodes contain cancer, usually the urologist will not proceed with a radical prostatectomy. Another form of treatment, usually hormone therapy and/or radiation therapy, is generally recommended. A pelvic lymph node dissection is most useful when it prevents an unnecessary prostatectomy from being performed. It is typically recommended for patients with clinical Stage III cancer or those with higher risk Stage I or II cancer who are considering surgical treatment.
A surgeon can perform a radical prostatectomy using different techniques including the following. Make sure you discuss the advantages and disadvantages of each technique, as well as your preferences, to determine which approach is best for you.,,,
Open Radical Prostatectomy
Radical prostatectomy can be performed through a low abdominal incision (retropubic) or through the perineum, the area between the scrotum and the anus (perineal prostatectomy). With the perineal approach, one cannot simultaneously remove the lymph nodes.
Minimally Invasive Surgery
Several recent studies suggest that minimally-invasive radical prostatectomy (MIRP) may be produce better outcomes than traditional open surgery—resulting in fewer post-surgical complications, fewer blood transfusions, and shorter hospital stays. Men with prostate cancer should speak with their physician to safely evaluate the risks and benefits of the different surgical procedures.,
Robotic-assisted Radical Prostatectomy (daVinci):
During Robot-assisted surgery the surgeon sits at a console near the operating table and performs the surgery by controlling robotic arms that hold the surgical instruments and a camera. Several small incisions are made in the lower abdomen. The instruments and camera are inserted into the patient’s body through these small incisions. The magnified, three-dimensional view provided by the camera, in combination with very small surgical instruments and highly maneuverable robotic arms, allow trained surgeons to work with precision. The ability to operate with increased precision can provide important benefits in urologic surgery. Organs such as the prostate are in a tightly confined area, and are close to nerves that affect urinary and sexual function. Avoiding damage to neighboring organs and structures is an important goal of surgery.,,
Cryosurgery is a technique that kills cancer cells by freezing them with sub-zero temperatures. During this procedure, hollow steel probes, guided by ultrasound, are placed inside and surrounding the cancer. Liquid nitrogen is then circulated through the probes, freezing the cancer cells and creating a ball of ice that surrounds the cancer. Once an adequate ice ball is formed, heated nitrogen is circulated through the probes. This process is then repeated. A heated probe is placed near the urethra throughout the freezing process so that the urethra is protected during the entire procedure. It is believed that cryosurgery creates cancer-killing effects through three distinct processes. First, ice crystals formed within cells are known to be lethal to nearly all cells. Second, when the ice forms around the cell, it draws water out of the cell, which collapses many of the walls or membranes within the cell. Third, when the ice surrounding the cells melts through the heating process, the water rushes back into the shrunken cell and causes it to burst.
This procedure has some compelling advantages, such as out-patient treatment, less pain, less blood loss, and faster recovery times. Since healthy tissue is preserved in the cancer-involved organ, the procedure can be repeated if the cancer returns.
The most serious complication associated with cryosurgery is when the rectal tissue is mistakenly frozen along with the prostate cancer. This complication has been reported in less than 1% of patients in several large studies. However, it is more likely to occur with a less experienced surgeon. The repair of this complication may require a temporary colostomy and additional surgery to close the hole between the rectum and the urethra. In one clinical trial, approximately 50% of the patients who had undergone cryosurgery were still impotent one year following surgery. The patients who may be the most appropriate candidates include older men over 70 years of age; patients who might have medical problems that would increase their risks of undergoing major surgery; or patients who have failed radiation therapy and have no other options.
Prostate cancer cells need male hormones (especially testosterone) in order to grow. Hormone therapy decreases the level of male hormones in the blood, which causes prostate cancer cells to die. Because hormone therapy can affect prostate cancer cells everywhere in the body, this treatment is used when cancer cells have escaped the prostate to other areas of the body. Prostate cancer that has spread to other areas of the body usually can be controlled with hormone therapy for a period of time, often several years. Eventually, however, most prostate cancers are able to grow despite the hormone therapy.
Bilateral orchiectomy (castration) is an operation to remove the testicles. By removing the testicles, the main source of male hormones is removed and hormone levels decrease. Orchiectomy is a common treatment for patients with metastatic (Stage IV) prostate cancer who will likely require hormone therapy for life. Patients may experience a benefit in symptoms in a matter of days following surgery.
Orchiectomy can cause side effects such as loss of sexual desire, impotence, hot flashes, and weight gain. The operation itself is relatively safe and not associated with severe complications. Because it is a one-time procedure, orchiectomy is a convenient and less costly method of hormone therapy.
Transurethral Resection of the Prostate (TURP)
Transurethral resection of the prostate (TURP) is a type of prostate surgery done to relieve moderate to severe urinary symptoms caused by an enlarged prostate, a condition known as benign prostatic hyperplasia (BPH). In this procedure, the cancer is cut out of the prostate gland using a small tool that can be inserted into the prostate through the urethra.
During TURP, a combined visual and surgical instrument (resectoscope) is inserted through the tip of your penis and into the tube that carries urine from your bladder (urethra). The urethra is surrounded by the prostate. Using the resectoscope, your doctor trims away excess prostate tissue that’s blocking urine flow and increases the size of the channel that allows you to empty your bladder.
The following section may answer additional questions that you have about undergoing surgery.
Radiation Therapy for Prostate Cancer
Radiation therapy, or radiotherapy, is a common way to treat early stage prostate cancer. Doctors who specialize in treating cancers with radiation are known as radiation oncologists. In radiation therapy, high-energy X-rays are used to kill cancer cells. In early-stage prostate cancer, radiation can be used instead of surgery, or it may be used after surgery to destroy any cancer cells that may remain in the area. In advanced stages of prostate cancer, it may be given to relieve pain or other problems.
Radiation therapy for early stage prostate cancer can be given in a variety of ways. The two most common ways are external beam radiation therapy and brachytherapy. External beam radiation therapy (EBRT) involves the delivery of radiation via a machine that aims X-rays at the body. During brachytherapy or interstitial implantation, a physician places small pellets or seeds of radioactive material directly into the prostate gland.
- External Beam Radiation Therapy
- Proton Beam Therapy
- Interstitial Brachytherapy
- Is Radiation Necessary after Prostatectomy?
- Side Effects From Radiation
- EBRT or Brachytherapy?
- Treatment of Bone Metastases
External Beam Radiation Therapy
External beam radiation therapy (EBRT) for prostate cancer is given on an outpatient basis, five days a week, for approximately six to eight weeks. EBRT begins with a planning session, or simulation, where marks are placed on the body and measurements are taken in order to line up the radiation beam in the correct position for each treatment. Patients lie on a table and are treated with radiation from multiple directions to the pelvis. The actual area of the pelvis receiving radiation treatment may be large or small, depending on the features of the cancer. Radiation can be delivered specifically to the prostate gland (prostate-only radiation) or encompass the surrounding pelvic lymph nodes in addition to the prostate gland (whole-pelvic radiation). Patients who are receiving treatment to a larger area of the pelvis may undergo another planning session to focus the radiation to the prostate gland, where cancer cells are greatest.
As the technology for delivering radiation therapy has evolved, important advances have been made in the ability of physicians to precisely target the area of the cancer with higher doses of radiation while sparing normal tissue to the extent possible. EBRT can be delivered more precisely in greater doses using a variety of newer techniques.
- Three-Dimensional Conformal Radiation Therapy (3D-CRT): 3D-CRT uses computers to precisely map the location of your prostate. Radiation beams are then shaped and aimed at the prostate from several directions, which makes it less likely to damage normal tissues.
- Intensity Modulated Radiation Therapy (IMRT): IMRT is an advanced form of 3D-CRT that allows doctors to customize the radiation dose by modulating, or varying, the amount of radiation given to different parts of the body being treated. The radiation intensity is adjusted with the use of computer-controlled, moveable “leaves” that either block or allow the passage of radiation from the many beams that are aimed at the treatment area. The leaves are carefully adjusted according to the shape, size, and location of the tumor. As a result, more radiation can be delivered to the tumor cells while less is directed at the normal cells that are nearby.
- Image-guided radiation therapy (IGRT): may be used in combination with other approaches such as IMRT. IGRT involves imaging during the course of radiation treatment, and is able to account for changes in the patient’s body or position that may shift the exact location of the cancer. The location of the prostate, for example, may vary somewhat depending on the contents of the bladder or rectum.
Proton Beam Therapy
Proton beam therapy focuses beams of protons instead of x-rays on the cancer. Protons are positive parts of atoms. Unlike x-rays, which release energy both before and after they hit their target, protons cause little damage to tissues they pass through and release their energy only after traveling a certain distance. This means that proton beams can, in theory, deliver more radiation to the prostate while doing less damage to nearby normal tissues.
Proton beams can be aimed with similar techniques to 3D-CRT and IMRT. Although early results are promising, so far studies have not shown that proton beam therapy is significantly better in the long-run than other types of EBRT. Thus far some but not all studies suggest that PBT may have fewer short term side effects however PBT is substantially more costly than IMRT and does not appear to produce a difference in toxicity 12 months after treatment.,
Internal radiation is known by a number of names: “interstitial brachytherapy,” “seeds,” or “implantation.” These terms refer to treatment where radioactive material is placed directly into the prostate gland. For prostate cancer, the most common method of interstitial brachytherapy is permanent implantation of radioactive seeds into the prostate gland through the perineum. The perineum is the area of skin between the scrotum and the anus. The implantation procedure is performed in the operating room while the patient is asleep or numb from the waist down. An imaging device known as an ultrasound is inserted into the rectum to visualize and guide placement of the seeds with needles into the prostate. After the procedure, the patient will temporarily contain a small amount of radiation from the seeds. Although this amount is not generally dangerous to most other people, some doctors may advise patients to avoid close contact with young children or pregnant women for several weeks.
Because implant radiation focuses the radiation closely around the prostate, this form of radiation works best in patients with early-stage prostate cancer. If the prostate-specific antigen (PSA) level or Gleason score is high, another form of treatment may provide improved results. Also, seed implantation does not work as well in patients who have had prior transurethral resection of the prostate (TURP), prior prostate infections, or in patients with large size prostate glands. There are 2 types of prostate brachytherapy. Both are done in an operating room and require some type of anesthesia.
Permanent (low dose rate, or LDR) Brachytherapy: In this approach, pellets (seeds) of radioactive material (such as iodine-125 or palladium-103) are placed inside thin needles, which are inserted through the skin in the area between the scrotum and anus and into the prostate. The pellets are left in place as the needles are removed and give off low doses of radiation for weeks or months. Radiation from the seeds travels a very short distance, so the seeds can put out a very large amount of radiation to a very small area. This lowers the amount of damage done to the healthy tissues that are close to the prostate.
Usually, anywhere from 40 to 100 seeds are placed. Because they are so small, the seeds cause little discomfort, and they are simply left in place after their radioactive material is used up. This type of radiation therapy requires spinal anesthesia (where the lower half of your body is numbed) or general anesthesia (where you are asleep) and may require an overnight stay in the hospital.
Temporary (high dose rate, or HDR) Brachytherapy: This is a newer technique. Hollow needles are placed through the skin between the scrotum and anus and into the prostate. Soft nylon tubes (catheters) are placed in these needles. The needles are then removed but the catheters stay in place. Radioactive iridium-192 or cesium-137 is then placed in the catheters, usually for 5 to 15 minutes. Generally, about 3 brief treatments are given, and the radioactive substance is removed each time. The treatments are usually given over 2 days. After the last treatment the catheters are removed. For about a week after treatment, you may have some pain or swelling in the area between your scrotum and rectum, and your urine may be reddish-brown.
These treatments are usually combined with EBRT given at a lower dose than if used by itself. The total dose of radiation is computed so that it is high enough to kill all the cancer cells. The potential advantage of this approach is that most of the radiation is concentrated in the prostate gland itself.
Possible Risks of Brachytherapy: If you receive permanent brachytherapy seeds, they will give off small amounts of radiation for several weeks. Even though the radiation doesn’t travel far, your doctor may advise you to stay away from pregnant women and small children during this time. You may be asked to take other precautions as well, such as wearing a condom during sex.
There is also a small risk that some of the seeds may move (migrate). You may be asked to strain your urine for the first week or so to catch any seeds that might come out. Be sure to carefully follow any instructions your doctor gives you. There have also been reports of the seeds moving through the bloodstream to other parts of the body, such as the lungs. As far as doctors can tell, this doesn’t seem to cause any ill effects and happens very rarely.
Radiation After Prostatectomy
A significant number of patients will still require postoperative radiation following radical prostatectomy because they are at an increased risk of cancer recurrence. Clinical studies have demonstrated that adjuvant radiation following radical prostatectomy may prolong the time until PSA recurrence, delay the use of hormonal therapy, and improve overall survival for certain patients.
Adjuvant radiation therapy is typically offered to high-risk patients following surgical prostatectomy. This includes individuals defined as high-risk and those found to have cancer involving the margins of the surgical specimen, seminal vesicle invasion, positive surgical margins, or extra prostatic extension following prostatectomy and individuals where the PSA remains persistently elevated.
The ideal time to deliver radiation therapy following radical prostatectomy is the subject of some debate. Radiation can be administered immediately after prostatectomy to high-risk individuals or in some cases delayed until there is evidence of PSA recurrence. The understanding of how best to use radiation following prostatectomy continues to evolve and patients should discuss the role and timing of radiation with their treating physician.
Side Effects From Radiation
Although patients do not feel anything while receiving a radiation treatment, the effects of radiation gradually build up over time. Many patients experience fatigue as treatment continues. Side effects increase with patient age and may be more or less common with EBRT or Brachytherapy. In general the occurrence of side effects continues to decrease as a result of more targeted radiation to the prostate. Its best to discuss the risk of various side effects with your treating physician as they can very significantly based on the institution and method of radiation delivery. Radiation may cause bowel and bladder dysfunction and impotence.,
Interstitial Brachytherapy or External Beam Radiation?
The decision to undergo radical prostatectomy, EBRT or radiation seed implantation is difficult. This is because these treatment strategies continue to evolve and improve making it difficult to directly compare them in well-designed clinical studies. The choice of radiation versus prostatectomy is often based on weighing the possible complications of treatment and the relative inconvenience of the treatments. It is important to be seen by more than one physician to determine the likely treatment outcome associated with the various options available in your community. Questions you may wish to ask your physicians include:
- What are the chances of this treatment curing the cancer?
- What is the risk of impotence and incontinence?
- What are the other possible complications from this treatment?
EBRT or Brachytherapy?
Radiation Therapy: Standard radiation therapy utilizes either external beam radiation (EBRT) consisting of daily treatments on an outpatient basis for approximately 6 to 8 weeks or interstitial brachytherapy, which involves permanent placement of radioactive seeds directly into the prostate gland. Because radiation implants focus the radiation closely around the prostate, this form of radiation works best in patients with stage I prostate cancer or low or intermediate risk stage II prostate cancer. For high-risk patients another form of treatment may be better suited for the patient. In addition, patients with a large prostate gland, prior history of prostate infections or recent transurethral resection of the prostate (TURP) may not be able to undergo the implantation procedure for brachytherapy. Patients should discuss the pros and cons of each with their treating physicain.,,
Treatment of Bone Metastases
Pain from bone metastases may also be relieved with radiation therapy directed to the affected bones. The side effects of radiation therapy for relief of bone pain depend on the area of the body being treated. Another method for treatment of bone pain is the use of radioisotopes which when given intravenously accumulates in the bones and kills prostate cancer cells by delivering small amounts of radiation. Clinical studies have shown that bone pain and the need for pain medications can be reduced in the majority of patients treated with a radioisotope. Since a radioisotope is given by vein, it can affect all bones in the body, whereas external radiation therapy is limited to only small areas of the body.
Systemic Therapy: Precision Cancer Medicine, Chemotherapy, and Immunotherapy
Systemic therapy is any treatment directed at destroying cancer cells throughout the body. Some patients with early stage cancer already have small amounts of cancer that have spread outside the prostate. These cancer cells cannot be treated with surgery or radiation alone and require systemic treatment to decrease the chance of cancer recurrence. More advanced cancers that cannot be treated with surgery can only be treated with systemic therapy. Systemic therapies commonly used in the treatment of prostate cancer include:
Chemotherapy: Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs. Chemotherapy drugs cannot tell the difference between a cancer cell and a healthy cell. Therefore, chemotherapy often affects the body’s normal tissues and organs, which can result in complications or side effects. In order to more specifically target the cancer and avoid unwanted side effects researchers are increasingly using precision cancer medicines.
- Chemotherapy is currently used mainly in men with advanced prostate cancer. The chemotherapy drug Taxotere® (docetaxel) was demonstrated to improve survival of men with metastatic prostate cancer in 2004 and has remained the mainstay of chemotherapy often utilized in combination with other chemotherapy drugs. In a study conducted by researchers at the Dana-Farber Cancer Institute, administered with androgen-deprivation therapy to metastatic prostate cancer patients was found to extend overall survival by more than 13 months. The results were reported at the 2014 American Society of Clinical Oncology (ASCO) meeting held in Chicago. The study included 790 men with hormone-sensitive metastatic prostate cancer. Patients were randomized to standard ADT or to ADT plus Taxotere, a chemotherapy drug. The primary endpoint of the study was overall survival. Due to a statistically significant survival difference observed between the two cohorts at an interim analysis, the trial was ended prematurely. After 29 months, 136 patients in the control arm had died, while 101 patients in the ADT plus Taxotere group had died. Men in the ADT/Taxotere arm had a median overall survival rate of 57.6 months; those in the ADT-only arm had a median overall survival of 44 months. Other markers of the disease—prostate-specific antigen (PSA) response, time to castration resistance, and time to progression prostate were also improved in the ADT/Taxotere cohort. For men with a high disease burden at the beginning of the study, the survival difference was even greater: a median overall survival of 49.2 months versus 32.2 months.,
Precision Cancer Medicines: Through genomic-biomarker testing performed on a biopsy or the cancer or from a blood sample doctors are increasingly able to define the genomic alterations in a cancers DNA that is driving the growth of a specific cancer. Once a genetic abnormality is identified, a precision medicine can be designed to target a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
- A Precision Cancer Medicine is one that is designed to target only the cancer cells and minimize damage to normal, healthy cells. Treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Advances in science and technology have led to the development of several different drugs for the treatment of prostate cancer over the past few years and doctors are working to determine the best sequence, combinations, and timing of utilization.
- Abiraterone (Zytiga®)
- Enzalutamide (Xtandi®)
- sipuleucel-T (Provenge®)
- Cabazitaxel (Jevtana®)
- Treatment of Bone Complications
- Zoledronic acid (Zometa®)
- Denosumab (Xgeva™)
- Radium Ra 223 dichloride (Xofigo®)
Cabazitaxel is administered intravenously and has been demonstrated to improve time to cancer progression and overall survival in men with HRPC previously treated with docetaxel. Cabazitaxel’s primary side effect is neutropenia, and it is recommended that patients receive a white blood cell growth factor if they are at high risk of this complication.
Immunotherapy: Precision immunotherapy treatment of cancer has also progressed considerably over the past few decades and has now become a standard treatment. The immune system is a network of cells, tissues, and biologic substances that defend the body against viruses, bacteria, and cancer. The immune system recognizes cancer cells as foreign and can eliminate them or keep them in check up to a point. Cancer cells are very good at finding ways to avoid immune destruction, however, so the goal of immunotherapy is to help the immune system eliminate cancer cells by either activating the immune system directly or inhibiting the mechanisms of suppression of the cancer.
Sipuleucel-T is actually an immunotherapy that prompts the body’s immune system to respond against the cancer. A Phase III clinical trial that contributed to the FDA approval of sipuleucel-T was a study known as IMPACT (Immunotherapy for Prostate AdenoCarcinoma Treatment) which demonstrated an improvement in overall survival for men treated with sipuleucel-T. The main side effects reported were chills, fever, and headache.
Testosterone is an androgen male hormone produced mainly by the testicles. Many organs in the body are composed of cells that respond to or are regulated by exposure to testosterone. Cells in the prostate have testosterone receptors and when exposed to testosterone, are stimulated to grow. When cells that have testosterone receptors become cancerous, the growth of these cancer cells can be increased by exposure to testosterone.
Hormone therapy, also known as androgen-deprivation therapy or (ADT), is designed to stop testosterone from being released or to prevent it from acting on the prostate cells and prevent the growth of cancer. Hormone therapy is primarily cytostatic; it prevents cancer cells from growing. It is not cytotoxic, like chemotherapy, which kills cancer cells. Hormone therapy may work for many years but eventually prostate cancer becomes resistant. When prostate cancer cells grow independent of or become insensitive to hormone therapy the cancer is referred to as hormone refractory and is known as hormone-refractory prostate cancer (HRPC).
Hormone therapy is increasingly being used before, during, or after local treatment and is a mainstay of the treatment of advanced prostate cancer. The type and timing of hormone therapy is an individual decision and one that should be discussed with your doctor. There are two methods of delivering hormone therapy:
Bilateral orchiectomy (castration) is a surgical operation to remove the testicles. By removing the testicles, the main source of testosterone is removed and hormone levels decrease. Orchiectomy is a common treatment for patients with metastatic (stage IV) prostate cancer who will likely require hormone therapy for life. Patients may experience a benefit in symptoms in a matter of days following surgery.
Orchiectomy can cause side effects such as loss of sexual desire, impotence, hot flashes, and weight gain. The operation itself is relatively safe and not associated with severe complications. Orchiectomy is a convenient and less costly method of hormone therapy; however, it is irreversible.
Medical Androgen Deprivation Therapy (ADT)
The second method of hormone therapy is to take medicines that produce the same effect as an orchiectomy. This is referred to as Androgen Deprivation Therapy (ADT). ADT slows or stops prostate cancer growth by reducing the exposure of the prostate to testosterone. Medicines that reduce male hormone levels are called LHRH analogues and anti-androgens. Female hormones such as estrogens can also reduce male hormone levels, but can also cause serious side effects and are therefore rarely used.
LHRH Analogues: Drugs that act like luteinizing hormone releasing hormone (LHRH) are known as LHRH analogues (Note that LHRH is sometimes called gonadotropin-releasing hormone (GnRH). These drugs turn off the signal for testosterone production by the testicles. By turning off the signal, hormone levels are reduced and cancer cells are not exposed to male hormones. LHRH analogues are typically given as a small injection under the skin of the abdomen every month or every three months. These drugs work just as effectively against prostate cancer as bilateral orchiectomy.
LHRH Antagonists—A newer class of medications can block LHRH from stimulating testosterone production without causing an initial testosterone surge. This class includes degarelix, which is given monthly to men as an alternative to orchiectomy or LHRH agonists.
LHRH analogues can cause side effects such as loss of sexual desire, impotence, hot flashes and the development of osteoporosis, which increases the risk of bone fractures. Because these drugs require an injection every 1 or 3 months, LHRH analogues may not be as convenient as an orchiectomy. Unlike orchiectomy however, these drugs can be discontinued, and male hormone levels gradually return to normal.
LHRH analogues may be used to treat patients with any stage of prostate cancer. When first taken, these drugs may increase prostate cancer growth and make a patient’s symptoms worse. This temporary problem is called “tumor flare.” Gradually, these drugs cause hormone deprivation, shrinkage of prostate cancer, and improvement in symptoms. Tumor flare can be prevented by administering an anti-androgen medication before the LHRH analogue. The LHRH antagonist degarelix, doesn’t cause a flare in testosterone.
- Leuprolide (Lupron, Eligard)
- Goserelin (Zoladex)
- Triptorelin (Trelstar)
- Histrelin (Vantas)
- Degarelix (Firmagon)
Anti-androgens: Not all male hormones are made by the testicles. A small amount of male hormone is made by the adrenal glands, and may not be affected by bilateral orchiectomy or LHRH analogues. An anti-androgen is a medication that can block the effect of the remaining male hormone on prostate cancer cells. Anti-androgens are pills often given to patients in addition to orchiectomy or LHRH agonists. This combination of treatment is known as total or combined androgen blockade (CAB).
Anti-androgens can cause side effects such as loss of sexual desire, diarrhea, enlargement of the breasts and occasional impotence. When used alone, these drugs appear to cause impotence much less often than other forms of hormone therapy. On rare occasion, these drugs can cause liver abnormalities, and blood tests can help detect these problems before serious side effects occur. These drugs can also be discontinued, and male hormone levels gradually return to normal. Anti-androgens are given as oral medications. They are usually prescribed along with an LHRH agonist or before taking an LHRH agonist to decrease risks associated with the hormone flare that can be caused by an LHRH agonist.
- Bicalutamide (Casodex)
- Nilutamide (Nilandron)
Newer hormonal medications that inhibit the synthesis of androgen (abiraterone) and block androgen receptor signaling (enzalutamide) are now FDA-approved for the treatment of metastatic prostate cancer after treatment with chemotherapy, and are being evaluated for use earlier in the disease, like when the PSA begins to rise or before chemotherapy.,,,,,
Abiraterone (Zytiga®) Abiraterone is an oral targeted agent that blocks the production of androgens not only by the testes, but also by the adrenal glands and the tumor itself. Abiraterone when administered with prednisone has been shown to improve quality of live and delay patient-reported pain progression in HRPC patients. Although this medication is generally well-tolerated, side effects may include fatigue, high blood pressure, and electrolyte or liver abnormalities and patients need to be monitored regularly.,,,
Enzalutamide (Xtandi®) Enzalutamide targets multiple steps in the androgen-receptor–signaling pathway, interfering with molecular pathways that help the prostate cancer grow. What’s more, the drug does not cause side effects commonly associated with chemotherapy, such as nausea and hair loss. Enzalutamide has been shown to improve survival, reduce the risk of cancer progression, and delay the need for additional chemotherapy in men with HRPC.,
Combined Androgen Blockage
Several clinical studies have directly compared CAB with a single form of hormone therapy (LHRH analogue or orchiectomy) for patients with metastatic prostate cancer. Two large studies conducted in the U.S. and Europe have shown improvement in disease control and survival with CAB. Most doctors feel CAB controls disease and improves survival better than either an LHRH analogue or orchiectomy alone.
Continuous vs. Intermittent Therapy
Intermittent Therapy: Some doctors believe that using medical hormone therapy intermittently can decrease the cost and reduce the side effects of treatment. When treatment is withheld for a period of time, sexual function and quality of life may improve. This was recently confirmed in a group of asymptomatic men with rising PSA levels after prostate cancer treatment. Men who received intermittent therapy appeared to have better quality of life, especially in terms of physical function, fatigue, urinary problems, hot flashes, libido, and erectile function and there was no difference in overall survival.
When to Start Hormonal Therapy
There is general agreement that men with advanced prostate cancer experiencing symptoms from should begin treatment immediately. There has been some disagreement, however, regarding the best time to start hormonal therapy in asymptomatic patients. Studies also suggest that men treated with immediate hormonal therapy lived longer without cancer progression and were less likely to develop significant complications from cancer compared to deferring hormone therapy until they developed symptoms.
Side Effects of Hormonal Therapy
Side effects of hormone therapy for prostate cancer may include the following. In general, the risk of side effects increases the longer you take hormone therapy medications.
- Bone thinning-Osteoporosis
- Erectile dysfunction
- Growth of breast tissue
- Heart disease
- Hot flashes
- Loss of sex drive
- Loss of muscle mass
- Memory problems
- Weight gain
Biological therapy is referred to by many terms, including immunologic therapy, immunotherapy, or biotherapy. Biological therapy is a type of treatment that uses the body’s immune system to facilitate the killing of cancer cells. Types of biological therapy include interferon, interleukin, monoclonal antibodies, colony stimulating factors (cytokines), and vaccines. Biologic therapies are being developed for the treatment of prostate cancer. Sipuleucel-T( Provenge®) is an immunotherapy that prompts the body’s immune system to respond against the cancer, and was the first to be approved by the FDA.
Sipuleucel-T is an immunotherapy that prompts the body’s immune system to respond against the cancer. A Phase III clinical trial that contributed to the FDA approval of Sipuleucel-T was a study known as IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment). The results of this study were presented at the 2010 Genitourinary Cancers Symposium, and the final results were published in The New England Journal of Medicine.
To evaluate the effect of Sipuleucel-T among men with metastatic, androgen-independent prostate cancer, researchers conducted a Phase III clinical trial known as IMPACT (IMmunotherapy for Prostate AdenoCarcinoma Treatment). The trial enrolled 512 men. Study participants were treated with either Sipuleucel-T or a placebo and then directly compared. Median overall survival was 25.8 months among men treated with Provenge compared with 21.7 months among men treated with placebo.
- Three-year survival was 31.7% among men treated with Sipuleucel-T compared with 23% among men treated with placebo.
- Sipuleucel-T did not significantly delay cancer progression.
- Side effects of Sipuleucel-T included chills, fever, and headache. Most of these side effects were low grade and of short duration.
The results of the study demonstrate that immunotherapy can be used in the management of prostate cancer; Sipuleucel-T improved overall survival among men with metastatic, androgen-independent prostate cancer.,
Treatment of Bone Complications
Patients with advanced prostate cancer can have cancer cells that have spread to their bones, called bone metastases. Bone metastases commonly cause pain, increase the risk of fractures, and can lead to a life-threatening condition characterized by an increased amount of calcium in the blood called hypercalcemia. Treatments for bone complications may include drug therapy or radiation therapy.
Zoledronic acid (Zometa®)
Zoledronic acid is a bisphosphonate drug and this class of drugs can effectively prevent loss of bone that occurs from cancer that has spread to the bones thereby reducing the risk of fractures, and decreasing pain. Bisphosphonate drugs work by inhibiting bone resorption, or breakdown. Zoledronic acid may be used to reduce the risk of complications from bone metastases or to treat cancer-related hypercalcemia.
Denosumab targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Studies have suggested that Denosumab may be more effective than Zoledronic acid at delaying bone complications in prostate cancer patients with bone metastases. Denosumab is associated with side effects including hypocalcemia (low levels of calcium in the blood) and osteonecrosis of the jaw (death of bone in the jaw).
Xofigo® (radium Ra 223 dichloride)
Radium 223 is a targeted radiopharmaceutical agent that binds with minerals in the bone to deliver radiation directly to bone tumors, thereby limiting the damage to the surrounding normal tissues. The U.S. Food and Drug Administration (FDA) approved the drug in May 2013 after a trial known as Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) was stopped early after an interim analysis showed that treatment with significantly improved survival.
By proactively understanding and managing aspects of your treatment, you can help ensure the best possible outcome from treatment and maintain some degree of control in your life. Things you can do to optimize treatment of cancer are:
- Get informed
- Stay organized
- Discuss the effectiveness of treatment
- Work with your physician to select the best treatment for you
Don’t forget that fighting cancer is not a challenge you should face alone. It is a team effort that involves family, friends, and your healthcare team. Don’t overlook the strength that can come from having your support network by your side. In order to ensure optimal treatment, consider the following:
Get informed: A new diagnosis of cancer can be a shock, making you feel out of control and overwhelmed. Getting informed can help alleviate these feelings. Seek out many resources to investigate your treatment options for your type and stage of cancer. Resources should include your healthcare team, second opinions, books, the internet, and other patients with your disease. As you learn, identify the specific questions that only your doctor can answer.
Most importantly, work toward understanding your diagnosis and stage of disease, goals of therapy, treatment plan, benefits of treatment, and possible side effects. Following a diagnosis of cancer, the most important step is to accurately define the stage of your disease. Staging is a system that describes how far the cancer has spread. (Keep in mind that some cancers, such as leukemia, may not be staged.) Each stage of cancer may be treated differently. In order for you to begin evaluating and discussing treatment options with your healthcare team, you need to find out from your doctor the correct stage of your cancer.
Stay organized: Develop a system for keeping all the information that you gather organized, such as laboratory and test results, admissions and consultation information, and additional instructions. Keep a folder or three-ring binder with all your information in one location.
Discussing the effectiveness of treatment: It is important that you and your caregivers are able to evaluate treatment options and to understand how cancer treatments are compared so that you can work with your healthcare team to make informed treatment choices. Understanding the goals of a specific therapy, as well as the risk and benefits it poses, will help you decide which treatment is most appropriate for your situation. Patients typically receive cancer treatment in order to cure the cancer, prolong the duration of their life or alleviate symptoms caused by the cancer and improve their quality of life. These potential benefits of treatment must be balanced against the risks of treatment. Some risks posed by various cancer treatments may include time away from family and friends, uncomfortable side effects of therapy and/or long-term complications or death.
The most common term used to describe the effectiveness of cancer treatment is remission. Remission means that the cancer has disappeared and can no longer be measured using existing technology. Oncologists use the terms partial and complete remission to describe partial or complete disappearance of cancer after treatment. A cancer cannot be cured if a remission is not obtained; however, a remission does not always ensure that a cancer is cured. The best ways to evaluate the benefits of treatment are to examine the duration of remission, survival, and disease-free survival (cure). Since it often takes many years to determine whether a new treatment is better than a previous treatment, remission rates may be useful for comparing therapies when patients have not been evaluated long enough to know whether the chance of cure or survival is improved.
Treatment of cancer is associated with risks. It is important that you evaluate the risks and benefits of treatment within the context of the overall goal of receiving cancer therapy.
Cancer treatment may be inconvenient, prolonged, or unavailable close to home. These are important considerations when evaluating treatment options, but not typically mentioned in medical journals reporting the results and benefits of new treatments.
Select your optimal treatment: Cancer treatment varies depending upon your type of cancer, stage of cancer, and overall condition. Additionally, treatment options may vary depending on whether or not the goal of treatment is to cure the cancer, keep the cancer from spreading, or to relieve the symptoms caused by cancer. You and your physician will consider all of these factors as you work on selecting your optimal treatment.
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