Early-Stage Prostate Cancer
- Active Surveillance
- Open – Radical Retropubic Prostatectomy (RRP)
- Open – Radical Perineal Prostatectomy (RPP)
- Laparoscopic Radical Prostatectomy (LRP)
- Robot-Assisted Laparoscopic Radical Prostatectomy (RALP)
- External Radiation Therapy
- High Intensity Focused Ultrasound (HIFU)
Advanced Prostate Cancer
- Androgen Deprivation Therapy
- Bilateral Orchiectomy
- LHRH Therapy
- Antiandrogen Therapy
- Estrogen Therapy
- P450 Enzyme Inhibitors
Hormone-Resistant Prostate Cancer
- Autologous Cellular Immunotherapy
- Systemic Radiation Therapy
- Estrogen Therapy
- P450 Enzyme Inhibitors
Early-Stage Prostate Cancer
Prostate cancer is diagnosed as early-stage when cancer cells have not spread outside of the prostate. If you’ve been diagnosed with early-stage prostate cancer with a low risk of progression—or you’re not expected to tolerate other therapies—your doctor may recommend watchful waiting or active surveillance. Aggressive treatment options include various types of prostatectomy, radiation therapy, cryosurgery, or high intensity focused ultrasound. The goal of all invasive options is to remove or destroy cancer cells before they can spread to other tissues in the body.
Watchful waiting forgoes implementing therapy or treatment unless symptoms arise or the prostate cancer spreads to other parts of the body.
Active surveillance is considered appropriate for some men with low-risk prostate cancer. This includes monitoring cancer with routine digital rectal exams (DREs), prostate-specific antigen (PSA) tests, and periodic biopsies. Active treatment, such as surgery or radiation therapy, does not occur unless there is evidence that it is growing.
The surgical treatment for localized prostate cancer is a radical prostatectomy, an operation that removes the entire prostate and both seminal vesicles and a portion of both vas deferens. Since it’s possible to perform this procedure without injuring the two pelvic nerves that enable an erection, the operation is referred to as a nerve-sparing radical prostatectomy and can be performed by a surgeon using any following prostatectomy options. Outcomes may vary depending on the skill level and experience of the surgeon.
Most often, nerve-sparing is used during early stages (Stages Tl and T2) when cancer cells are located only within the prostate. Some surgeons are skilled in nerve-sparing techniques to maximize the preservation of nerves, muscles, organs, and other structures surrounding the prostate. If the nerves are not damaged during surgery, men have a better chance of having erections again between two and 18 months after the operation. Potency rates following nerve-sparing radical prostatectomy vary widely among surgeons and academic centers.
Open – Radical Retropubic Prostatectomy (RRP)
An incision is made from just below the navel to the pelvic bone without damaging muscles. This allows the surgeon access to feel the prostate, surrounding tissues, and the pelvic lymph nodes, which can help the surgeon decide if a nerve-sparing radical prostatectomy is the best option based on cancer. If all areas feel smooth, the nerves can be saved because they probably are not cancerous. However, if the surgeon feels a lump, hardness, or any other abnormality near the nerve, the safest approach is to remove one or both nerves. There is no accurate way to confirm whether or not cancer is present in a pelvic nerve unless the nerve is removed and analyzed by a pathologist.
Open – Radical Perineal Prostatectomy (RPP)
The incision for this procedure is between the scrotum and the anus. While there is less blood loss with this operation compared to the retropubic procedure outlined above, the surgeon still has the ability to feel along the pelvic nerves to determine whether they can be saved or must be removed. Recovery is generally faster compared to the RRP, and patients have less blood loss.
Laparoscopic Radical Prostatectomy (LRP)
Also referred to as “minimally invasive” or “keyhole surgery,” the operation begins by inserting a needle into the abdomen to inflate it with carbon dioxide, thereby separating the abdominal wall from the organs and providing the space necessary to perform the surgery. Three or four small incisions are made in the lower abdomen as access for surgical instruments and a telescopic lens that projects images onto a video monitor. After the prostate has been cut away from the bladder and the urethra, it’s removed from the body through an incision made above the pubic bone.
Robot-Assisted Laparoscopic Radical Prostatectomy (RALP)
As with the laparoscopic procedure described above, this operation also begins by inserting a needle into the abdomen to inflate it with carbon dioxide, thereby separating the abdominal wall from the organs and providing the space necessary to perform the surgery. Three or four small incisions are made in the lower abdomen as access for surgical instruments and a telescopic lens that is attached to robotic arms, which are connected through special cables to instruments providing the surgeon with robotic control of the procedure through a three-dimensional view of the inside of the abdomen shown on a video monitor. After the prostate has been cut away from the bladder and the urethra, it is removed from the body through an incision above the pubic bone.
Advantages of Prostatectomy
- One-time procedure
- May cure early-stage prostate cancer (if cancer cells are only located in the prostate) May prevent the spread of cancer to other tissues
- Removes the prostate gland and the problem of future overgrowth of the prostate (called BPH—benign prostate hyperplasia—the non-malignant enlargement of the prostate)
- May help extend life, especially if performed correctly
Disadvantages of Prostatectomy
- Requires hospitalization
- May cause impotence (also known as erectile dysfunction (ED), the inability to get an erection of sufficient quality to penetrate or to fulfill the sexual act)
- May cause incontinence (loss of urinary control)
- May cause narrowing of the urethra, making urination difficult
- 20% incidence of morbidity
External Beam Radiation
External beam radiation is a treatment for prostate cancer that uses a machine to deliver rays of high energy. It works on the DNA, which is contained in all living cells. DNA controls the ability of cells to divide. Cancer cells harm us because they continue to divide without stopping. The energy from radiation machines is so strong that it can damage the DNA in cancer cells, causing them to die or making them unable to divide. Prostate cancer is most commonly treated using gamma rays. However, treatment can also be accomplished with alpha, beta, proton, and neutron particles. External Beam Radiation can be used to treat prostate cancer that has not spread beyond the prostate (Stages T1 and T2)
- Often used in combination with hormone therapy if cancer cells have spread beyond the prostate to nearby tissues (Stage T3) or if the cancer is an intermediate risk (PSA 10-20 ng/ml, Gleason 7, T2B)
- May be used for pain relief in prostate cancer that is no longer responding to hormone therapy and has spread to other tissues in the body, primarily bones (Stage M+)
- External Beam Radiation Therapy (EBRT): radiation is generated and administered by a machine outside the body, usually in brief daily sessions for several weeks.
- Intensity-Modulated Radiation Therapy (IMRT) minimizes radiation damage to normal tissues by using many narrow beams rather than a single wide beam, thereby allowing for greater control of the dose of radiation.
- 3-Dimensional Conformal Radiation Therapy (3DCRT) treatment allows closer targeting of the prostate gland. Uncontrolled studies suggest better outcomes with IMRT compared to 3dCRT; however, definitive proof is lacking at this time.
- CyberKnife Robotic System is a non-invasive treatment option for prostate cancer that has the ability to deliver targeted and destructive doses of radiation from almost any angle to the body. It tracks tumor motion and automatically corrects the aim of the treatment beam when movement is detected. Studies have not determined if it offers clear clinical advantages. Additional information at http://www.cyberknife.com/
- The Calypso Tracking System (GPS for the body) was designed to improve IMRT radiation by adjusting for any movement of the prostate by placing tiny sensors in the gland before the treatment begins to emit radiofrequency waves that allow for the very accurate alignment of a man’s prostate before each treatment session. It can also be used to monitor the position of the prostate at all times during radiation treatment delivery, objectively pinpointing the location of tumors and helping to minimize the amount of healthy tissue surrounding the prostate or prostate tumor that might be radiated due to organ movement.
- Proton Beam Therapy (PBT) uses proton beams instead of x-rays to kill cancer. Proponents believe it offers an ability to deliver more precise radiation; however, no well-done study has demonstrated any clinical advantage over IMRT. Besides, it is far more costly. Recently, the American Society of Therapeutic Radiation (ASTRO) recommended that PBT for prostate cancer only be done as part of a randomized study or a multi-institutional database. Learn more about PBT by visiting The National Association of Proton Therapy website.
- Permanent Brachytherapy (“seeds”) introduces radiation from small radioactive seeds (about the size of a grain of rice), which are inserted directly into the prostate. The radiation emitted from the seeds gradually declines until they are no longer active. Seeds are inserted with the patient under anesthesia and are too small to cause discomfort.
- High-Dose Rate (HDR) Brachytherapy provides short-term internal radiation that uses higher dosage, non-permanent seeds.
- Systemic Radiation Therapy uses radiation delivered by the injection of a radioactive compound to control pain caused by metastasized (Stage M+) prostate cancer that no longer responds to hormone therapy.
Advantages of Radiation Therapy
- Avoidance of major surgery
- May cure prostate cancer in its early stages and can help extend life or eliminate symptoms in later stages
- Most side effects are minor and decrease after therapy stops, especially when appropriate IMRT, seeds technique, and equipment are used
Disadvantages of Radiation Therapy
- Organs naturally move during treatment, and the doctor sometimes cannot predict which way or how much organs will move. Organ movement can be caused by breathing, gas in the intestines or rectum, blood flow through the circulatory system, and other natural bodily functions. When your organs move, the tumor may not get the right amount of radiation, or other nearby organs may receive radiation they should not get.
- May cause damage to healthy cells, leading to side effects
- Skin reactions
- Frequent and painful urination
- Upset stomach
- Rectal irritation or bleeding
- Urinary incontinence
- Erectile dysfunction
- Small increased risk of bladder and colon cancer
- A small percentage of patients will have significant bleeding from the bladder many years after prostate radiation treatment. This is called hemorrhagic radiation cystitis.
Cryotherapy uses freezing temperatures to kill prostate cancer cells.
- The technique has improved since first introduced in the 1960s, and with new advances, it is more reliable and with fewer complications, especially if performed correctly.
- Used to treat localized prostate cancer (Stages T1 and T2) and recurrent cancer following radiation therapy
- Freezes and immediately kills prostate cancer cells.
- Performed under anesthesia, uses the ultrasound-guided placement of cooling probes into the prostate.
- Hormone therapy can be used before cryosurgery to decrease prostate size.
- Long-term effectiveness unknown
Advantages of Cryosurgery
- Avoids major surgery
- Less likely to cause urinary tract damage, obstructions, or bowel difficulties than radiation
- The procedure takes about an hour and a half or less, and patients often fully recover within days
Disadvantages of Cryosurgery
- Impotence due to nerve damage is a common occurrence
- Urinary incontinence can occur but is rare
- Approximately 2% of men develop an abnormal tissue mass (fistula) that connects the rectum and the bladder that may require surgery to repair
High-Intensity Focused Ultrasound (HIFU)
HIFU is a state-of-the-art technology ablation technique that has been used to treat thousands of cases of prostate cancer worldwide. HIFU is a treatment that uses the energy from ultrasound waves to produce very high temperatures of about 100°C or 212°F delivered to the prostate through a probe inserted into the rectum after spinal or epidural anesthesia has been administered. Some of the advantages of using HIFU as your primary prostate cancer treatment are listed below:
The probe emits a beam of high intensity focused ultrasound
- At the point where the ultrasound is focused (focal point), the sudden and intense absorption of the ultrasound beam quickly raises the temperature, which destroys targeted cells
- The area destroyed by each beam is tiny and precise
- By repeating the process and moving the focal point, it is possible to destroy the prostate tissue
- The treatment takes from 1 to 3 hours depending upon the size of the prostate and is usually performed on an outpatient basis
Advantages of HIFU
- Destruction of the cancerous tissue with no risk of injury to the surrounding organs
- No danger of rectal injury
- The patient does not undergo any radiation exposure
- Usually, no hospital stay is required, typically outpatient procedure
- Treatment is performed under spinal or epidural anesthesia
- Treatment can be repeated if necessary
- Other radiation treatments or surgery can be performed along with HIFU. Patients who develop recurrence remain candidates for surgery, radiation, or hormone therapy.
- Other therapeutic alternatives can be considered in case of incomplete results.
- A nerve-sparing procedure can be performed
- Focal therapy, hemi-therapy, or whole gland therapy can be performed
- Long term side effects are low, such as bleeding and frequency of urination
- No cuts on the body
- Almost all patients maintain potency, which is common with other procedures
Disadvantages of HIFU
- No pathology (no tissue) to be examined following the procedure
- Not covered by many insurance plans.
- The long term data on results is still under evaluation. Short term 5-10 year data appears to be comparable to surgery and radiation.
Further information about HIFU can be found at www.edap-tms.com and www.internationalhifu.com
2) Advanced Prostate Cancer
Prostate cancer is considered advanced when cancer cells have spread to other parts of the body—or metastasized. When cancer has spread beyond the prostate, complete removal of the prostate or destruction of cancer tissue by radiation or cryosurgery is unnecessary. For stage T3 and T4 prostate cancer, studies show that combining ADT with radiation can improve survival.
Types of Hormone (Androgen Deprivation) Therapies
Prostate cancer cells require male hormones (such as testosterone) to grow. Hormone therapy decreases the production of testosterone by the testicles so that cancer cell growth slows down. The term most commonly used for this treatment is called androgen deprivation therapy (ADT.) May also be used in early-stage prostate cancer (Stage T2) in combination with radiation therapy or prior to surgery to reduce the size of the prostate and make it easier to remove
- Types of hormone therapy:
- Surgical removal of the testicles (bilateral orchiectomy)
- Drug treatment that lowers testosterone levels reduces the effect of testosterone or adrenal androgens from acting on the prostate or minimizes the conversion of testosterone to dihydrotestosterone (DHT), a powerful stimulus for prostate cell growth
- Common side effects of reducing male hormone activity by hormone therapy (listed in order of most to least common):
- Osteoporosis (bone weakening)
- Loss of muscle mass and an increase in body fat
- Hot flashes
- Reduced libido and impotence
- Anemia (decreased level of red blood cells)
- Gynecomastia (breast enlargement)
Bilateral orchiectomy is an operation that removes both testicles, which produce 95% of the body’s testosterone.
- Simple orchiectomy is the removal of both testicles through a cut (incision) in the scrotum. If desired, artificial testicles (saline implants) can be inserted into the scrotum.
- Subcapsular orchiectomy is the removal of the tissue from the lining of the testicles where testosterone is made. This leaves a nearly normal-looking scrotum.
Advantages of Orchiectomy
- One-time procedure
- Effective, permanent reduction in testosterone
- Patients typically go home the same day as the surgery
- Cost-effective treatment (relatively inexpensive)
Disadvantages of Orchiectomy
- Side effects, such as reduced or absent sexual desire, impotency, hot flashes, and emotional impact make this procedure difficult for some patients to accept, although side effects are similar to medical castration
- Irreversible surgical procedure
- Will not allow for intermittent androgen deprivation (IAD) therapy
The administration of an injectable luteinizing hormone-releasing hormone (LHRH) agonist or antagonist that causes a decrease in testosterone level.
Currently available LHRH agonists:
- Lupron® (leuprolide acetate)
- Eligard® (leuprolide acetate)
- Viadur® (leuprolide acetate implant)
- Vantas® (histrelin implant)
- Zoladex® (goserelin acetate)
- Trelstar™ (triptorelin)
Advantages of LHRH Agonists
- Easy administration of injections monthly or every 1, 3, 4, 6, or 12 months
- Treatment with LHRH agonists is as effective as orchiectomy in reducing testosterone levels.
- Side effects can be mostly reversible upon the termination of the treatment with IAD therapy.
Disadvantages of LHRH Agonists
- Side effects of hormone therapy may be challenging to treat and hard for some people to accept
- Testosterone level rises during the first two weeks of initiating therapy (flare response), which may cause an increase in cancer symptoms in some men
- Requires injections every 1, 3, 4, 6, or 12 months
- A common side effect is hot flashes, which many men find bothersome. These hot flashes can be minimized with a variety of medications, including low dose estrogen and progesterone
The administration of an injectable gonadotropin-releasing hormone (GnRH) receptor antagonist provides rapid, profound, and sustained suppression of testosterone.
Currently available GnRH receptor antagonists:
- Firmagon® (degarelix for injection) – indicated for the treatment of advanced prostate cancer (similar indication as LHRH agonists)
Advantages of GnRH Receptor Antagonists
- Reduces testosterone levels quickly without the initial “testosterone surge” seen with an LHRH agonist. Hence, Antiandrogen therapy is not needed to prevent possible flare symptoms.
- Reversibly binds to the GnRH receptors in the pituitary gland, immediately suppressing the secretion of the luteinizing hormone (LH), follicle-stimulating hormone (FSH), and subsequently, testosterone and PSA levels.
- GnRH receptor antagonists are at least as useful as LHRH agonists to lower testosterone levels and sustaining castrate levels.
- Easy subcutaneous (just under the abdominal skin) injections monthly
Disadvantages of GnRH Receptor Antagonist
- The overall rate of adverse reactions is similar to leuprolide.
- Injection site reactions are mostly transient and of mild to moderate intensity, except for initial treatment.
- Must be given monthly
The administration an antiandrogen blocks the action of male hormones, including testosterone and androgens, released by the adrenal glands and used in combination with LHRH agonist therapy in a strategy called maximal androgen blockade (MAB) or combined androgen blockade (CAB). The antiandrogen is continued until the PSA rises. Studies show more prolonged survival with MAB compared to ADT alone. When PSA rises, stopping antiandrogen can result in short-term benefits.
Currently available antiandrogens in the U.S.:
- Casodex® (bicalutamide)
- Eulexin® (flutamide)
- Nilandron® (nilutamide)
Advantages of Antiandrogen Therapy
- May provide a small survival advantage over either orchiectomy or LHRH analog therapy alone
Disadvantages of Antiandrogen Therapy
- In addition to the common side effects of hormone therapy, side effects are:
- Breast pain or enlargement
- Gastrointestinal pain
- Adverse effects on liver function (possible elevation of liver enzymes that must be monitored)
5-alpha reductase (5-AR) Inhibitors
Blocks conversion of testosterone to DHT is a more potent stimulator of prostate cell growth than testosterone.
Currently available 5-AR inhibitors:
- Proscar®, Propecia® (finasteride) – reduces DHT levels in the blood by 70% to 90% on the prostate.
- Avodart® (dutasteride)– reduces DHT levels in the blood by 98% and slows prostate cell growth.
Advantages of 5-AR Inhibitors
- Reduces the normal prostate cell growth and prostate size
- May reduce the risk of recurrence following surgery
Disadvantages of 5-AR Inhibitors
- Not approved as a treatment for prostate cancer
- No evidence it influences the survival of men
- Causes only modest reductions in PSA levels (15-20%) when used alone
Administration of estrogen hormones lowers testosterone production and has some direct apoptotic effects on both androgen-dependent and androgen-independent prostate cancer cells.
Currently available estrogen therapies:
- DES (diethylstilbestrol)
- Stilphosterol® (stilbestrol diphosphate)
- Estraderm® patch (estradiol) – only a few small-scale trials have investigated the benefits of delivering estrogen through the skin (transdermal) to block testosterone production in men with prostate cancer. A patch successfully reduces testosterone levels, with fewer cardiovascular or other side effects (gynecomastia). Phase III trials comparing the results of the patch and injected forms of estrogen in men with prostate cancer are currently underway.
Advantages of Estrogen Therapy
- Does not cause bone loss
- Does not induce androgen-independent cancer growth
- Can dramatically slow the growth of some prostate cancer cell types
Disadvantages of Estrogen Therapy
- Will cause gynecomastia, unless prevented by breast irradiation
- Depending on the route of administration, it may promote hypercoagulation of blood, causing blood clots in the legs, lungs, heart, and brain. No evidence that blood thinners significantly reduce the risk of clots
- Increased incidence of heart attacks
- Causes decreased libido and impotence
- Risk of cardiovascular side effects is reduced when treatment is given a patch or injectable drug rather than by mouth
P450 Enzyme Inhibitors
The P450 enzymes are involved in synthesizing several hormones, including testosterone, that stimulates prostate cancer cell growth. Inhibitors of these enzymes can decrease the levels of testosterone and adrenal androgens, and have direct cytotoxic effects on prostate cancer cells.
Available P450 enzyme inhibitors:
- Nizoral® (ketoconazole used in combination with hydrocortisone)
Advantages of P450 Enzyme Inhibitors
- May be useful in men for whom CAB has failed (who are androgen resistant)
- Reduces both testicular testosterone and adrenal androgen production
- Additional cytotoxic effect on prostate cancer cells
Disadvantages of P450 Enzyme Inhibitors
- Not approved in the U.S. for treatment of prostate cancer
- Requires continued use of LHRH agonists or estrogen therapy to block pituitary stimulation of testicular hormone production (unless the patient had an orchiectomy)
- Non-selective effects on other cells may cause discomfort (nausea, gastric irritation)
- May have significant adverse effects on liver function (must measure liver enzymes)
Hormone-Resistant Prostate Cancer
Prostate cancer that is no longer responsive to hormone therapy is referred to as hormone-resistant prostate cancer, hormone-refractory prostate cancer (HRPC), castrate-resistant prostate cancer (CRPC), or androgen-independent prostate cancer. Several new therapies have been approved in the past several years to treat CRPC. More studies are needed to determine the optimal sequencing of these new treatments.
Zytiga® (Abiraterone Acetate)
The oral agent that has been approved in combination with prednisone for CRPC. It acts by inhibiting an enzyme complex called CYP-17 that is necessary for producing testosterone. Studies show that this enzyme is present in the adrenal gland and prostate cancer cells.
- Oral agent
- Prolongs survival in men with CRPC
- Must be given with prednisone
- Must be taken on an empty stomach
- Side effects occur including hypertension, increased potassium level, and fluid retention
For more information about Zytiga, visit zytiga.com.
An oral agent approved for men with CRPC after patients’ progress on chemotherapy. The FDA is currently considering approval for men before chemotherapy. It works by interfering with androgen receptor signaling in prostate cancer cells.
- Oral Agent
- Prolongs survival
- Side effects can occur, including asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain
- May increase the risk of seizures
For more information about XTANDI, visit xtandi.com.
Autologous Cellular Immunotherapy
Provenge® (sipuleucel-T) can be prescribed to treat asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer. Provenge is the first in a new class of autologous cellular immunotherapies that use a patient’s own antigen-presenting cells (APCs) to stimulate the body’s immune system against prostate cancer. Provenge is given by intravenous (IV) infusion in three doses, approximately two weeks apart over a month. Blood is collected a few days before each infusion. The total course of therapy is generally completed, given in four to six weeks.
- Minimal typical side effects compared to other treatment options
- Prolongs survival of men with CRPC
- Does not interfere with the effectiveness of other therapies
- The most common side effects reported with Provenge treatment (usually occurring within the first few days of treatment) are chills, fatigue, fever, back pain, nausea, joint ache, and headache; other side effects are also possible
- Rarely, Provenge can cause severe acute reactions resulting from the infusion, which typically occur within one day of infusion
- Does not lower PSA or produce a measurable objective response
- Costly, but covered by most insurance companies, including Medicare
For more information on Provenge, visit www.Provenge.com.
Systemic Radiation Therapy
Xofigo® (Radium-223) was recently approved to treat symptomatic bone metastases in men with CRPC.
- The treatment administered as a one-time injection
- Improves survival in men with symptomatic bone metastases
- Patients are still eligible for chemotherapy
- Side effects include nausea, vomiting, diarrhea, low blood counts
Also, see the sections on radiation therapy and treating the pain associated with advanced prostate cancer for further details. For more information on Xofigo, visit Xofigo.com.
The administration of potentially toxic drugs that circulate throughout the body and eliminate rapidly growing cancer cells
- Also, affect rapidly-growing healthy cells, which can lead to side effects
- The dose and frequency of chemotherapy treatments are carefully controlled to minimize harm to healthy cells
- Reserved for patients with advanced-stage cancer that does not respond to hormone therapy (Stage M+)
- Currently, available chemotherapy drugs indicated for prostate cancer:
- Taxotere® (docetaxel)- Phase III randomized studies have shown that Taxotere in combination with either Prednisone or Estramustine can significantly improve survival on average by 2 months in patients with hormone-resistant prostate cancer
- Jevtana®(cabazitaxel) – indicated in combination with prednisone for the treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-based treatment regimen
- Novantrone® (mitoxantrone; specifically approved for hormone-resistant prostate cancer)- Studies show it improves the quality of life but do not increase survival
- Emcyt® (estramustine)
Advantages of Chemotherapy
- May prolong survival
- Provides cancer symptom improvement
Disadvantages of Chemotherapy
- Side effects
- Hair loss
- Nausea and Vomiting
- Reduced blood clotting
- Lowered white cell count and increased risk of infection