Treatment & Management of Prostate Cancer
Medically reviewed by Dr. C.H. Weaver M.D. 1/2021
The choice of prostate cancer treatment is influenced by a 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.
Several different doctors may be involved with the diagnosis and management of prostate cancer including a urologist, radiation oncologist and a medical oncologist. Urologists are surgeons who specialize in treatment of disorders of the male genital tract, including prostate cancer. Radiation oncologists use various forms of radiation to treat prostate cancer and medical oncologists are often involved when systemic chemotherapy or precision cancer medicines are required.
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.
Local Treatment of Prostate Cancer
Surgery is used to diagnose, stage, and treat prostate cancer and performed by a urologist. Surgical removal of the prostate is considered a local treatment and is very effective treatment if the cancer has not spread beyond the prostate. (1-4)
Radiation Therapy - During 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. (5-10)
Hormone Therapy - 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. This can be done using medications or surgical castration by removal of the testicles. (3,4,11,12)
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. Genomic testing may help determine whether active surveillance or watchful waiting is a good treatment option.
Role of Surgery in Prostate Cancer
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. Nearly all patients with prostate cancer will have some kind of surgery. Surgery may be used to perform a biopsy in order to obtain tissue 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 typically performed on an outpatient basis.
- Prostate Biopsy - 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. Patients should discuss the role of NGS testing on their biopsy and consider a liquid biopsy as well.
- 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 and performance of a "nerve sparing" prostatectomy is preferred in order to not damage the nerves that control the bladder and erections. 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. (1-5)
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). 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. 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.
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. (2-4)
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. (5)
Prostate cancer cells need male hormones (especially testosterone) in order to grow. Bilateral orchiectomy (castration) is an operation to remove the testicles which produce the testerone. 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 the less costly method of hormone therapy. (4)
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. Historically radiation was administered five days a week, for approximately six to eight weeks, however treatment schedules have been decreased using more intensive radiation dosing resulting in many patients only requiring 5-6 days of intensive radiation.
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. (2,3)
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. (6)
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. (6-8)
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. (19)
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.(19)
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. (19,20)
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 physician. (19,20)
Hormonal Therapy - Androgen Deprivation Therapy
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 or castration resistant and is referred to as castration resistant prostate cancer (CRPC).
Hormone therapy may be 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. Surgical orchiectomy or medical androgen deprivation therapy are two methods of delivering hormone therapy for early stage disease.
Surgical Orchiectomy - bilateral orchiectomy (castration) is a surgical operation to remove the the testicles - the main source of testosterone. 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 - utilizes 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. Lupron (leuprolide) is the most widely used but the FDA approved Orgovyx in 2021 as the first oral therapy and its availability reduces the need for in person clinic visits which is especially beneficial in helping patients with cancer stay home and avoid exposure during the coronavirus pandemic.
These drugs work just as effectively against prostate cancer as bilateral orchiectomy.
LHRH Antagonists - a 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. (22)
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.
- Leuprolide (Lupron, Eligard)
- Orgovyx (relugolix)
- 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.
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. (4)
Continuous vs. 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. (24)
Newer hormonal medications that inhibit the synthesis of androgen Zytiga (abiraterone) and block androgen receptor signaling Xtandi (enzalutamide) are now FDA-approved for the treatment of advanced prostate cancer.
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. Zytiga 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. (25)
Xtandi® (exnzalutamide) - 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 Xtandi has been shown to improve survival, reduce the risk of cancer progression, and delay the need for additional chemotherapy in men with HRPC. (26,27)
Erleada™ (apalutamide) is an androgen receptor inhibitor that works by binding directly to the ligand-binding domain of the AR. Erleada™ inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription.
When to Start Hormonal Therapy
There is general agreement that men with advanced prostate cancer experiencing symptoms 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.
Treatment of Advanced Prostate Cancer
More advanced cancers cannot be treated with surgery or radiation because the cancer cells have already spread away from the prostate gland. Systemic therapies commonly used in the treatment of prostate cancer include the following and doctors work to determine the best sequence of treatment in order to delay cancer progression and prolong survival. Systemic therapy is any treatment directed at destroying cancer cells throughout the body and typically consists of additional ADT or a precision cancer medicine followed by immunotherapy, chemotherapy and or bone directed treatment in individuals with advanced prostate cancer no longer responding to ADT.
Androgen Deprivation Therapy
- Zytiga® (zbiraterone)
- Xtandi® (Enzalutamide)
Precision Cancer Medicines
- Lynparza (olaparib)
- Taxotere (docetaxel)
- Jevtana® (Cabazitaxel)
- Novantrone (mitoxantrone)
Treatment of Bone Complications
- Denosumab (Xgeva™)
- Xofigo (Radium Ra 223 dichloride)
Precision Cancer Medicines - Cancer cells may differ from one another based on what genes have mutations. Precision cancer medicine requires molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome to identify specific genetic abnormalities that can be targeted. Once a genetic abnormality is identified, a specific targeted therapy that attacks a specific mutation or other prostate cancer-related change in the DNA programming of the cancer cells can be selected for treatment. This “genomic testing” is performed on a biopsy sample of the cancer and increasingly in the blood using a “liquid biopsy” In 2020 Lynparza was the first precision cancer medicine approved for the treatment of men with prostate cancer and BRCA1 and BRCA2 gene mutations which are critical for DNA damage repair (DDR) and present in ~ 5-10% of prostate cancer patients. All men with prostate cancer should undergo genomic testing to determine if they have cancer causing mutations treatable with a precision cancer medicine. (18) All patients with prostate cancer should undergo genomic biomarker testing for BRCA, and other potential targets. Learn more here...
Immunotherapy - is a type of treatment that uses the body’s immune system to facilitate the killing of cancer cells. Types of immunotherapy therapy include interferon, interleukin, monoclonal antibodies, colony stimulating factors (cytokines), and vaccines. 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. (16,17)
Chemotherapy - 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, Taxotere administered with ADT to metastatic prostate cancer patients was found to extend overall survival by more than 13 months. Men in the ADT/Taxotere arm had a median overall survival of 57.6 months; those in the ADT-only arm had a median overall survival of 44 months.
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( Provenge®) - 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) which demonstrated an improvement in overall survival for men treated with sipuleucel-T. The main side effects reported were chills, fever, and headache.
Treatment of Bone Metastases
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.
Xgeva™ (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) (28)
Xofigo® (radium Ra 223 dichloride) - 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. (29)
Zoledronic acid (Zometa®) 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.
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