The prostate is a gland found in men at the base of the bladder surrounding the urine outflow channel (urethra).
It is involved in ejaculatory function during sexual intercourse. Prostate cancer is the most common internal tumor in US males and the second leading cause of cancer death in US men, behind lung cancer. According to the American Cancer Society, one in six men will be diagnosed with prostate cancer at an average age of 67. In 2012, an estimated 241,740 men will be diagnosed, and 28,170 men, will die of prostate cancer.
In an attempt to diagnose prostate cancer early, while it is confined to the prostate gland, screening is performed either by a primary care provider or a urologist. This is necessary because early, organ-confined prostate cancer is almost always asymptomatic. Advanced prostate cancer may present with bone pain, difficulty with urination or blood in the urine.
There are several known factors which increase the risk for prostate cancer:
- having a first-degree relative (a father or brother) diagnosed at under 65 years old
- being African-American
- increasing age
While prostate cancer screening recommendations vary between the American Cancer Society (ACS), the American Urologic Association (AUA), and the National Comprehensive Cancer Network (NCCN), in general it is felt that prostate cancer screening should start between 40 and 50 years of age. Men who are at a very high risk with multiple risk factors should start screening annually at age 40. Men with one risk factor are considered to be at moderate risk and should be screened every 2-5 years starting at age 40. Men without any risk factors can start annual screening at age 50. It is recommended that screening stop once men reach 75 years old, or have a life expectancy less than ten years.
Screening involves a blood test to check the prostate specific antigen (PSA) level and a digital rectal exam (DRE) in which a physician places a finger in the rectum and feels the prostate, looking for irregular areas or nodules in the prostate gland which may represent cancer. The exam takes only a few seconds. The PSA blood level can be influenced by multiple factors, so an elevated PSA does not necessarily mean that prostate cancer is present. Additionally, the PSA may be within normal and there could still be cancer present detected by DRE alone.
Normal Age Specific PSA Range by Race (ng/ml)
|Age (years)||Caucasian||African American||Asian American|
Table 1: Normal Age Specific PSA Range by Race (ng/ml)
Elevated PSA can occur for many reasons and does not necessarily mean that prostate cancer is present. PSA can be elevated above the race and age-adjusted limits in men with recent sexual activity or prostate manipulation, prostate infection, a large prostate, or prostate cancer. If the PSA is elevated without any obvious reason, like infection, a prostate biopsy is often recommended to rule out cancer as the cause for elevation. Prostate biopsy is also recommended if a suspicious nodule is felt during a DRE.
Prostate cancer cannot be definitively diagnosed unless a prostate biopsy is performed. This is a procedure done in a urologist’s office. An ultrasound probe (a little bit bigger than the size of one’s thumb) is placed into the rectum and under ultrasound-guidance, a small needle is used to take samples of different areas of the prostate gland. Prior to taking any biopsy samples, local anesthetic is injected at the base of the prostate to minimize discomfort. This procedure is generally well-tolerated and can be successfully done in clinic to avoid the unnecessary risks of general anesthesia.
There are risks involved with a biopsy of the prostate. The most common side effects include blood in the urine, stool, and ejaculate (30-60%). These symptoms are normal and expected after this procedure. Persistent bleeding requiring intervention occurs in less than one percent of patients and almost only in patients on blood-thinning medications like aspirin, Plavix or Coumadin. Major side effects do occur but are rare. Serious infection (0.6%) and urinary retention (1.2%) are the most concerning. Transient fevers can occur in about 6% of patients.
In order to minimize the risks of the procedure, patients should usually stop taking blood thinning medications one week prior to biopsy. They are also prescribed oral antibiotics and an enema the morning of the biopsy. If the patient develops urinary retention (inability to urinate), a catheter may be placed in the bladder for a few days until the swelling of the prostate goes away.
After the biopsy, patients should refrain from sex for a few days, but otherwise can resume normal daily activity the next day. It takes about five to seven days to get the biopsy results back.
Once the biopsy results are available, the patient will return to clinic to discuss them with their urologist. If the results are negative, the patient will resume annual screening with DRE and PSA. If they are positive, the physician will discuss the aggressiveness of the cancer. The physician may also recommend imaging studies, like a CT scan or a bone scan. They will also discuss which types of treatment are appropriate for that type of cancer.
Interpretation of Biopsy Results and Risk Stratification
If a patient’s prostate biopsy comes back as positive for cancer, the patient is then placed into a risk category: low, intermediate or high. The risk category is determined by the biopsy results, the PSA and the DRE.
Patients should know into which risk category they fall, but it is not necessary to understand how that risk is determined. For those who are interested, the following paragraphs explain risk stratification.
The aggressiveness of prostate cancer is determined by several factors: Gleason score, PSA and clinical stage. Based on these factors prostate cancer can either be classified as low, intermediate or high risk.
The first determining factor is the Gleason score. The Gleason score is assigned by the pathologist (the doctor who looks at the biopsy under a microscope). The score is a number from 6-10. This number represents the disorganization of the glands seen under a microscope. The more disorganized the glands, the higher the score and the more aggressive the cancer.
PSA is a second determinant of prostate cancer risk. A PSA less than 10ng/mL is considered low risk. PSA of 10-20ng/mL is considered intermediate risk, and PSA above 20ng/mL is high risk.
The last determinant of risk is the clinical stage. Clinical staging is determined by the method of detection (DRE vs. PSA) and other imaging, if felt necessary by the urologist.
Staging of Prostate Cancer with Associated Risk
|T1||Clinically inapparent tumorneither palpable or visible byimaging||Low|
|T1b||>5% found on specimen afterbenign prostate surgery||Low|
|T1c||Tumor found on biopsy afterelevated PSA||Low|
|T2||Tumor confined to prostate, asdetermine by DRE||Low or intermediate|
|T2a||Tumor in one half of one lobe orless on DRE||Low|
|T2b||Tumor in more than one half ofone lobe but not both lobes on DRE||Intermediate|
|T2c||Tumor in both lobes on DRE||Intermediate|
|T3||Tumor extending beyondprostatic capsule on DRE||High|
|T3a||Extra capsular extension on DRE||High|
|T3b||Tumor invades seminal vesicleon DRE||High|
|T4||Tumor is fixed or invadesadjacent structures on DRE||High|
Table 2: Staging of Prostate Cancer with Associated Risk
- Once PSA, Gleason score, and clinical staging have been completed, risk can be assigned.
Summary of Prostate Cancer Risk Stratification
|Intermediate||PSA 10-20, Gleason score 7, Stage T2b or T2c|
|High||PSA>20, Gleason 8 or higher, Stage 3 or higher|
Table 3: Summary of Prostate Cancer Risk Stratification
Once again, it is not necessary for a patient to be able to understand how to determine their own risk, but they should know their risk classification, as their risk will influence which therapies will be recommended. It is important for the patient to discuss with his physician if there is a need for additional tests to check for “cancer spread”. Men with low risk cancer DO NOT REQUIRE ADDITIONAL TESTS as the risk of cancer spread is very minimal. For patients who fall into intermediate or high risk groups, the urologist may order a bone scan, CT scan, or chest X-ray to evaluate for spread of cancer to the bones, lymph nodes, or other sites.
Treatment (Active surveillance, Surgery, Radiation (Brachy vs XRT), Androgen Deprivation Therapy, Other)
There are many options for treatment of prostate cancer. There is no ‘right’ treatment; the decision should be individualized after discussion with a patient’s doctors and family. This section provides a brief summary of each treatment modality with the pros and cons.
Active surveillance means closely following prostate cancer activity but delaying treatment until the cancer shows signs of becoming more aggressive. Active surveillance is frequently an option for low-risk prostate cancer and sometimes (but much less often) for men in intermediate or high-risk groups . Active surveillance involves regular PSA and DRE checks as well as a repeat prostate biopsy in 1-2 years. Biopsy may be done earlier if triggered by a rise in PSA or a concerning DRE. If repeat biopsy shows cancer progression, then treatment is warranted.
The benefit of active surveillance is patients avoid the side effects of surgery, radiation, or hormone therapy. The downside is that the patient theoretically risks progression of the cancer. However, studies have shown that the cure rate is similar between men who undergo treatment at the time of diagnosis and men who choose active surveillance and then undergo delayed treatment. About 30% of men undergoing active surveillance will undergo treatment within 5 years of diagnosis.
Surgery involves removal of the prostate with or without removal of pelvic lymph nodes. This is an option for patients in whom the cancer appears to be confined to the prostate gland. The benefit of surgery is that if the cancer is truly confined to the prostate gland, the cancer can be completely removed and the patient can be cured. In addition, if lymph nodes are removed, the pathological stage can be determined, which can help determine if any additional treatment would be beneficial. Lastly, if the cancer comes back or if the pathology suggests there may be disease left behind (for example, if the cancer had spread slightly outside the prostate gland), radiation therapy remains an option for treating any residual disease.
Side effects from prostate surgery include immediate erectile dysfunction and urinary incontinence. Urinary incontinence occurs because of damage to the nearby muscles that control urinary function. All patients should expect to have some leakage after surgery. Within four months of surgery, about 70% of patients no longer require incontinence protection; one year after surgery, that number rises to 90%. Patients who continue to have leakage can undergo several different therapies, including physical therapy exercises and surgery, to help this resolve.
The nerves that control erectile function are microscopic and run on the edges of the prostate. Surgery can be individualized to try and spare the nerves; however, due to their microscopic size and proximity to the prostate, minor injury cannot be avoided. In patients with higher-risk disease or disease known to be located near these nerves, nerve-sparing procedures are not recommended. Erectile function continues to improve up to two years after surgery. Even though erectile function is expected to decrease after surgery, therapies like oral medications, vacuum devices, penile injections and even further surgery can be tried to achieve satisfactory erectile response.
In contrast with radiation therapy, erectile dysfunction and urinary incontinence are seen immediately after surgery. In addition to erectile dysfunction and urinary incontinence, other known side effects could include incomplete resection of tumor requiring subsequent radiation, urine leak, pelvic bleeding, and bladder neck contracture (scarring at the connection between the urethra and bladder). Surgical removal of the prostate can either be done open, with a midline incision from belly button to the pubic bone, or robitic-assisted laparoscopy, with five to six smaller incisions across the abdomen. There is no evidence to date that cancer-control is better with one type of procedure or the other.
There are different forms of radiation that can be used depending on prostate cancer risk:
- External Beam
- Permanent seed implant or low dose brachytherapy
- Temporary implant or high dose radiation brachytherapy
A formal consult with a radiation oncologist should be obtained in order to discuss radiation options. External beam radiation therapy involves delivering daily treatments to the prostate for approximately 8 weeks. Brachytherapy involves placing radioactive seeds into the prostate. These seeds dispense radiation to the prostate over one to seven months. Temporary implant involves placing needles in the prostate and delivering a blast of radiation and then taking the needles out. Brachytherapy can be used alone for low risk cancer or in combination with external beam radiation with or without hormone ablation therapy in intermediate or high risk cancer. Newer forms of radiation therapy: Proton Beam Radiation and Hypofractionation Radiation Therapy are currently under investigation. The advantage of radiation is that it is less invasive than surgery and side effects like erectile dysfunction are delayed. Drawbacks include erectile dysfunction, bladder irritation (chronic and severe in
Androgen Deprivation Therapy (ADT)
Also known as hormone ablation therapy, ADT blocks production of testosterone and/or blocks the testosterone receptor in the prostate. Since prostate cancer usually requires testosterone to grow, these medications can block the growth of prostate cancer. Medical oncologists sometimes are consulted to help administer this therapy, although many urologists administer it as well. This medication is typically given every 3-4 months as a subcutaneous injection in the stomach. The same results can also be achieved surgically with removal of the testosterone-producing tissue in the testicles.
ADT can be used in combination with radiation (either as a primary treatment or after surgical removal of the prostate gland) or in patients in whom prostate cancer has recurred. It is not an initial treatment by itself. ADT in combination with certain radiation therapies can reduce long term cancer recurrence.
In patients who have primary treatment and then experience a recurrence (eg. a PSA rise), ADT is considered first line therapy once surgery and radiation are no longer options. ADT is also used for known metastatic disease. Short term side effects include hot flashes and gynecomastia (swelling and tenderness of breast tissue). Long term complications include increased risks of diabetes, cardiovascular disease, anemia, sexual dysfunction, and osteoporosis.
Cryotherapy is freezing of the prostate with transrectal probes performed under anesthesia. Prostate tissue is frozen to -40 degrees Celsius in two cycles under ultrasound guidance. Side effects include temporary urinary retention, temporary genital swelling, temporary decreased penile sensation, erectile dysfunction, urethral sloughing, rectal pain, urinary incontinence, and rare fistula formation.
There are other therapies for prostate cancer such as High Intensity Focused Ultrasound (HIFU), proton beam radiation therapy, and others. These are often promoted as less invasive and equally effective with fewer side effects. However, because these therapies are relatively new, long term data is not available to truly assess their efficacy or side effects profiles. Because of these unknowns, these treatments are not considered the gold standard therapies that surgery and radiation are considered to be.
Surveillance and Salvage Therapy
Once a patient undergoes initial treatment for his prostate cancer, the PSA should become undetectable or at least drop significantly from the pre-treatment value (expectations vary depending on the treatment modality). The patient must then undergo continued surveillance for prostate cancer recurrence. This surveillance is most often accomplished with annual PSA testing. Patients with low-risk disease have a lower risk of recurrence; patients with intermediate- and high-risk disease are at increased risk of recurrence.
A PSA rise, known as ‘biochemical recurrence’, may require further treatment. Further treatment can also be warranted if a patient develops radiographic evidence of cancer spread. The type of treatment recommended depends on the extent of recurrent disease, and on the treatments already administered. ADT is often indicated at this time.
If the PSA is seen to rise in spite of ADT, the cancer is said to be ‘castrate-resistant’. In this case, there are newer medications that may control the cancer for long periods of time. At present there are two chemotherapy medications: Taxotere and Cabazitaxel, an additional hormonal medication (second-line hormone) with Abiraterone Acetate and a vaccine, Sipuleucel-T.