Treatment Options for Prostate Cancer

BY MARK SCHOLZ, MD

Selecting treatment for prostate cancer is complex. Start by taking the Staging Quiz (keytopc.com). This is the first-step to understanding proper management.  Once you know your stage can you focus on the treatments considered optimal for you. This blog post introduces the most common treatments used for prostate cancer.

Active Surveillance

Active surveillance means monitoring the cancer without any immediate treatment. This is the recommended approach for SKY and Low-TEAL.   Surveillance consists of imaging the prostate with a multiparametric MRI and/or a color Doppler ultrasound once a year. In addition, PSA, a blood test, is checked 3 or 4 times a year.

Computerized Beam Radiation (IMRT, SBRT, IMPT)

Beam radiation, which is targeted at the prostate gland and sometimes to the surrounding lymph nodes, comes in several forms: IMRT, SBRT, and IMPT.  Compared to older technology, called conformal beam radiation, side effects of computerized beam radiation are greatly reduced. Computerized targeting and a new gel spacer called SpaceOAR protect the rectum and reduce radiation exposure to the normal tissues surrounding the prostate. IMRT and IMPT treatments are typically administered daily, Monday through Friday, for five to nine weeks.  SBRT is completed in two weeks or less. Potential side effects of beam radiation are fatigue, erectile dysfunction and urinary issues such as pain with urination.  Beam radiation is often combined with Testosterone Inactivating Pharmaceuticals (TIP) and seed implants (see below).

Chemotherapy

Chemotherapy consists of injected medications that circulate through the bloodstream to halt cancer cell replication. Taxotere (docetaxel) and Jevtana (cabazitaxel) are the most common chemotherapy drugs used for prostate cancer. They are given intravenously every three weeks. As chemotherapy agents go, these medications tend to have fewer side effects compared to other types of chemotherapy. The most common side effects are modest fatigue and hair loss. Nausea is very rare or is easily countered with anti-nausea medication.

Focal Therapy (HIFU, Laser, Cryotherapy, Electroporation)

Standard radiation and surgery target the whole prostate gland, not the cancer within. Focal treatments direct tumoricidal energy only at the cancer, while sparing the remainder of the uninvolved gland.  Focal therapy reduces the risk of unpleasant side effects. However, by sparing portions of the prostate there is a risk that the cancer may not be totally eradicated. Focal therapy requires careful patient selection. For example, men with bilateral disease or with cancers located very close to the urethra are poor candidates.  Focal therapy also requires great precision and technical skills.  Curing the tumor, while minimizing collateral damage to the incredibly sensitive surrounding structures, requires extensive training and experience.

Immunotherapy

Presently, Provenge is the only FDA-approved immunotherapy for prostate cancer. Blood is removed from the patient in a dialysis-like procedure and processed in a lab where specific immune cells called dendritic cells are “trained” to recognize prostate cancer cells. After processing, the dendritic cells are infused back into the patient where they stimulate “killer T-cells” to attack the prostate cancer. Provenge requires three infusions administered over six weeks. Side effects are modest or nonexistent.   New research is being conducted and the future of immunotherapy looks very promising. 

Seed Implants (Brachytherapy)

Radioactive seed implants are placed within the prostate gland. Since all the radiation stays inside the gland, the surrounding normal tissues of the body are spared from radiation exposure.  There are two types of seed implants: High-Dose Radiation (HDR) and Low-Dose Radiation (LDR). For HDR, hollow catheters are inserted into the prostate and the HDR seeds are temporarily pushed through the catheters into the gland.  Several sessions are scheduled during a short hospital stay.  After treatment is completed, the catheters are removed.  For LDR, radioactive seeds are implanted permanently in the prostate gland during a one to two-hour outpatient procedure. LDR seeds emit a continuous low dose of radiation over 3 to 8 weeks, depending on the type of implant (Cesium, Palladium or Iodine).  Seed implants can be used as a standalone therapy for Basic-TEAL or combined with external beam ration and TIP for more advanced stages.  Side effects are similar to beam radiation, though some studies suggest that the incidence of urinary side effects is slightly higher with seed implants.

Surgery

Until the beginning of the new millennium, after which radiation technology radically improved, surgery was rightly considered “The Gold Standard.”  Cure rates were higher than the old-fashioned, conformal type of radiation and incidence of urinary and sexual side effects was similar. Now, compared to modern radiation, the advantages of doing surgery are less clear.  Everyone who has surgery is initially impotent and less than one-fifth of men fully recover. Permanent shrinkage of the penis is very common. In addition, everyone is initially incontinent and requires a catheter. Most men eventually recover a relatively decent degree of urinary control but stress incontinence (leakage with coughing, jumping, sneezing, and laughing) continues to be a chronic problem in about 50% of patients. In addition, at least 20% of men are troubled with lack of urinary control during sexual activity.

Injected Radiation

In advanced and more serious stages, prostate cancer spreads into the bones. Xofigo is a type of targeted radiation (radium 223) administered by injection that concentrates in cancerous spots in the bone, attacking the cancer wherever it is located.  Xofigo is administered monthly for a total of six injections. Side effects are usually minimal though some may experience mild transient nausea or diarrhea. 

Testosterone Inactivating Pharmaceuticals (TIP)

Testosterone stimulates prostate cancer growth. TIP blocks testosterone and causes the cancer to regress, often dramatically. The intensity of the testosterone blockade varies depending on the type of therapy. The mildest agents are the orally-administered 5-alpha-reductase inhibitors such as Proscar (finasteride) and Avodart (dutasteride). At the next level of intensity are the oral anti-androgens called Casodex (bicalutamide) and Nilandron (nilutamide).  Even stronger blockade can be achieved with the LHRH agonists and antagonists, which completely shut down the production of testosterone from the testicles. Common LHRH agonists are Lupron, Zoladex, Eligard, Trelstar, Vantas, and Firmagon.  These products are given by injection monthly, quarterly, semi-annually, or yearly. If resistance to the above agents occurs, even stronger agents such as Zytiga or Xtandi are available. These oral medications are the strongest hormone blocking agents available. Zytiga works by blocking the cancer cell from manufacturing its own testosterone. Xtandi blocks the activity of testosterone within the cancer cell.  Side effects of TIP treatment varies greatly between patients.  Fatigue, weight gain, hot flashes, and loss of libido are some of the most common.  Once TIP is stopped, the side effects reverse.  

Final Thoughts

Selecting optimal treatment using powerful anticancer agents requires extensive training and experience. As noted above, optimal treatment intensity will vary according to the stage of disease. In addition, adjustments in treatment sequence, dosage, and timing may be necessary to account for differences in patient age and overall health status. In some cases, when greater treatment intensity is needed, multiple agents can be used in combination. Alternatively, in elderly or frail patients, treatment intensity can be ratcheted down by reducing a medication’s dosage or by extending the time between treatment cycles.