Prostate Cancer
by G. Alivizatos, M.D., PhD, Urologist

Introduction

Prostate cancer is the most common malignancy in the Western World, accounting for almost 15% of all diagnosed male cancers and approximately 5% in undeveloped countries and it is the second most common cause of cancer death in men. It is calculated that a man in developed countries has a 16% of lifetime risk of being diagnosed with prostate cancer and a 2.57% risk of dying from this disease.

Risk factors for prostate cancer development include increasing age, animal fat consumption, ethnic origin and a family history.

About 95% of prostatic carcinomas are adenocarcinomas. Squamous cell carcinoma and other types such as signet-ring carcinoma, transitional carcinoma, neuroendocrine carcinoma or sarcoma are the remaining 5%.

 

Grading and Staging

The grading of prostatic adenocarcinoma is performed according to the Gleason score.

The staging of prostate cancer follows the Tumor, Lymph Nodes and Metastasis (TNM) classification systemTherefore, prostate cancers are classified based on these 3 characteristics; an example classification could be "T2N0M0".

The TNM classification and the corresponding meaning is presented below.

T - Primary tumor
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor not apparent clinically, not palpable or visible by imaging
T1a    Tumor incidental histological finding in 5% or less of tissue resected
T1b    Tumor incidental histological finding in more than 5% of tissue resected
T1c    Tumor identified by needle biopsy (e.g. because of elevated Prostate-Specific Antigen [PSA] level)
T2 Tumor confined within the prostate
T2a    Tumor involves one half of one lobe or less
T2b    Tumor involves more than half of one lobe, but not both lobes
T2c    Tumor involves both lobes
T3 Tumor extends through the prostatic capsule
T3a    Extracapsular extension (unilateral or bilateral) including microscopic bladder neck involvement
T3b    Tumor invades seminal vesicle(s)
T4 Tumor is fixed or invades adjacent structures other than seminal vesicles: external sphincter, rectum, levator muscles, and/or pelvic wall
N - Regional lymph nodes
NX Regional lymph nodes cannot be assessed
N0 No metastasis to regional lymph node(s)
N1 Regional lymph node metastasis
M - Distant metastasis
MX Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a    Non-regional lymph node(s)
M1b    Bone(s)
M1c    Other

As a result, the above example of classification T2N0M0 would mean a tumor

  • confined within the prostate (T2)
  • without regional lymph node metastasis (N0) and
  • without distant metastasis (M0).

 

Screening

The introduction of screening based on the combination of Digital Rectal Examination (DRE) and serum Prostate Specific Antigen (PSA) testing has increased the opportunity for earlier diagnosis at lower stages of the disease.

Screening is a controversial issue because of the risk of overdiagnosis and overtreatment.

The American Association of Urology (AUA) has recently released new guidelines in which they:

  1. do not recommend PSA screening in men under the age of 40 years
  2. do not recommend PSA screening in men between ages 40 to 54 at average risk
  3. do recommend a shared decision making for men ages 55-69 years
  4. do recommend a screening interval of >2 years and
  5. do not recommend PSA screening in men >70 years or in men with a life expectancy ranging from less than 10 years up to 15 years.

The European Association of Urology (EAU) has a slightly different position upon PSA screening. The updated EAU guidelines do not recommend widespread mass screening, but early detection in well informed men with a life expectancy of more than 10 years is recommended.

Both institutions, therefore, agree that widespread screening is not recommended but in men with a life expectancy >10 years. The suggested way to proceed is for patients to be informed by their doctor about the existing dilemmas, including the detailed advantages and disadvantages of every decision taken from PSA measurement to agressive therapy.

Therefore, a shared path between patients and doctors is advisable; it is important to remember that every decision is individualized and risk factors such as age, comorbidity, family history and ethnicity should influence the chosen strategy.

 

Diagnostic strategies for early detection

 

Markers

The Prostate Specific Antigen (PSA) is the best marker for prostate cancer. However, the measurement of this marker does not always give the correct answers, and therefore many more markers are being investigated and used in clinical practice.

Among these new markers, the ones with the most promising contribution are:

  • Free PSA and pro PSA (serum markers)
  • PCA3 and TMPRSS2 (urine markers)

 

Imaging

Currently, the most important tool in the diagnostic process is the "Transrectal ultrasonography of the prostate" (TRUS), as all prostatic biopsies are performed under this guidance. It is rapid, effective and radiation free

Lately, a technique called "polyparametric Magnetic Resonance Imaging (MRI)" has been used as a diagnostic tool as well, but it still remains an expensive approach with questionable results.

 

Nomograms

Nomograms are complicated prediction models developed in order to predict the risk of having a positive biopsy for prostate cancer. The actual purpose of these nomograms is to avoid unnecessary biopsies without missing men with aggressive tumors.The urine marker PCA3 has been used for such a purpose.

 

Treatment Options

Treatment of prostate cancer depends upon the stage of the disease.

For localized cancers there are three options:

  1. Active surveillance (for low risk cases)
  2. Local radiotherapy
  3. Radical prostatectomy.

 

Active Surveillance

Thanks to screening and early detection, many prostate cancers are first detected long before they pose a threat, and many men with prostate cancer will die from causes other than prostate cancer. Specific measures can be used to identify men at lower risk of disease progression during intermediate periods of follow-up, which although imperfect, include:

  • tumor properties (grade, volume, PSA, stage)
  • patient characteristics (age and comorbidities). 

For men with lower risk cancer or for those for whom avoidance of sexual, urinary, and/or bowel complications are a primary consideration, active surveillance may also be considered. It is believed that this approach could be appropriate for 40% of all men diagnosed with the disease.

Active surveillance does not mean "doing nothing". Men are regularly monitored with PSA tests, digital rectal exams, imaging, and follow-up biopsies to make sure the cancer has not progressed. The use of ultrasound, Computed Tomography (CT) scans, bone scans, or MRI scans might also be used to watch for disease growth and the need for treatment. A proportion of men who choose active surveillance may eventually need treatment. The risk that by waiting you might miss the window of best opportunity for treating the cancer has been found to be rather small.

 

Types of Radiation Treatment for Prostate Cancer

Radiotherapy for prostate cancer can be divided into two types: external beam radiation therapy and brachytherapy.

In external beam radiotherapy, a small amount of radiation is delivered in daily increments to the prostate, generally Monday through Friday over a course of 7 to 8 weeks. Currently, 3D Conformal Radiation Therapy (3DCRT) or Intensity Modulated Radiation Therapy (IMRT) is used to deliver high-dose radiation to the prostate while minimizing toxicity to the surrounding normal structures such as the bladder and rectum.

Prostate brachytherapy is a radiation technique in which radioactive seeds are implanted directly into the prostate. The seeds are delivered through the perineal skin into the prostate using needles that are inserted into the prostate using ultrasound guidance. Both low-dose rate (but high-dose) permanent prostate seeds and high dose rate (HDR) temporary implants can be used to treat the gland successfully. Prostate brachytherapy is typically performed in an outpatient setting under either general or regional anesthesia. The procedure is usually well tolerated with a low risk of surgical complications.

The relative effectiveness of external beam radiation and brachytherapy appear to be similar for early stage prostate cancer. Some patients are offered the combination therapy in which both external beam radiation and brachytherapy are utilized. For men with locally advanced cancer and/or aggressive (e.g. Gleason score of 7 or higher) cancer, androgen deprivation is also added to improve cancer control.

The main side effects of radiotherapy include bladder and rectal toxicities which can result in urinary and bowel dysfunction. Erectile dysfunction is also common and appears to increase with time after treatment. The long-term effects of radiation to normal tissues remain unknown though an incidence of secondary malignancy appears to be higher in this population.

 

Surgery for Prostate Cancer

Many different surgical approaches are used in prostate cancer, each with its own risks and benefits. As with any surgery, the outcome depends in large measure on the expertise of the surgeon. It is crucial for you to find a surgeon with extensive experience in performing the chosen type of surgery.

  • Focal therapy: For low risk tumors, focal therapy is a new investigational treatment option with minimal side effects. With the help of Magnetic Resonance Imaging (MRI), the goal is to identify the exact location of the tumor within the prostate, and then the tumor is treated with the local application of an energy source. The long term effectiveness of this option still needs verification through longer follow up periods.
  • Open radical retropubic prostatectomy involves removing the prostate through a cut made in the lower abdomen. This technique allows surgeons to remove not only the prostate but also any nearby lymph nodes that have become cancerous. Nerve-sparing techniques are now widely used to preserve urinary control and sexual function. The operation typically requires 2-3 days in the hospital. Most men need a urinary catheter in place for 1-2 weeks after the surgery. For cancers confined to the prostate, radical prostatectomy remains the most effective way to remove cancer.
  • Robot-assisted radical prostatectomy is performed through 5-6 tiny “keyhole” cuts in the lower abdomen. Manipulating robot-like fingers that pass through these cuts, surgeons can remove the diseased prostate with minimal disturbance to healthy surrounding tissue. The technique also allows surgeons to remove cancerous lymph nodes. The main advantages of this robot-assisted prostatectomy are less blood loss, a shorter hospital stay and faster recovery time from surgery. The oncological and functional outcomes of the robotic procedure seem to be similar to the open procedure.

 

Hormone Therapy for Prostate Cancer

Hormone deprivation therapies are applied in case of

  • metastases present at the time of diagnosis or
  • disease progression evident after the implementation of local radical therapy (radical prostatectomy or radiation therapy).

Male sex hormones, mostly testosterone, provide the fuel that drives prostate cancer growth. Hormone therapy does not kill cancer cells but can significantly shrink tumors and slow any further growth. Side effects include loss of sex drive, impotence, nausea, diarrhea, and fatigue.

Hormone therapy takes 3 forms:

  1. LHRH agonists. These medications are injected once a month, once every three to four months, or once a year, depending on the specific drug. If these treatments are used instead of surgery, these drugs must be administered regularly for life.
  2. Anti-androgens prevent prostate cancer cells from using testosterone. They are taken in the form of a pill. This type of therapy is not given by itself, but is used in combination with other hormonal therapies.
  3. Orchiectomy involves the removal of the testicles, which reduces testosterone production by about 90%. (About 10% of testosterone is produced by the adrenal glands.) This approach is sometimes chosen by older men who do not want the inconvenience or expense of taking medications. 

 

Follow-up strategies

The best way to follow the efficacy of any chosen treatment is to measure the serum levels of Prostate Specific Antigen (PSA).

After radical prostatectomy, the PSA value should be less than 0.2ng/ml and after radiation therapy a good value is <0,5ng/ml.

The PSA is usually measured every 3 months during the first year after the termination of a radical treatment and every 4 months during the second year. CT scans and bone scans are not necessary in cases with stable and undetectable PSA values, as only when a significant PSA rise is noticed they might be used to identify the metastatic site.

 

Prognosis

In 85% of all cases, prostate cancer is a slow progressive disease.

Today the majority of cancers are diagnosed when the disease is locally confined and therefore, whatever treatment is applied, the prognosis is good.

The Gleason score, the stage of the disease and the initial PSA value are thoroughly studied prognostic parameters. However, the outcome cannot be predicted on an individual basis.

Recently, a lot of attention has been given in the identification of gene sequences that might predict the possibility of recurrence and might help urologists to decide when and how to intervene.

 

Content on this site is not a substitute for professional medical advice. You should always consult your doctor.