The prostate is a male endocrine organ that is normally the size of a golf ball. The primary function of the prostate is in male fertility by secreting enzymes and nutrients that promote sperm motility and enhance fertilization of the female egg. Without a prostate a man is not fertile. The prostate does not secrete male hormones and does not play a role in sexual function. Thus men can maintain normal sexual function even after the prostate has been removed. As men age the prostate frequently grows in size and can often block the flow of urine. The condition of “enlarged prostate” is called benign prostatic hyperplasia or BPH. In other words for most men an “enlarged prostate” is not caused by prostate cancer, but rather a non-cancerous condition. Prostatitis is another common benign condition that affects the prostate. Men affected by prostatitis often complain of pain in the perineal or rectal area as well as urinary frequency.

Prostate cancer is the most common non-skin cancer in United States men and the second leading cause of cancer related deaths (figure 1). It was estimated that in 2006 234,460 men were diagnosed with, and 27,350 men died of prostate cancer. The lifetime risk for a man in the United States to be diagnosed with prostate cancer is 1 in 6. All men can get prostate cancer but those with a family history and African American men are at a substantially greater risk. Although the exact cause of prostate cancer is not known it has been suggested the high fat diets are associated with increased prostate cancer risk while diet rich in fish and fruits and vegetables can reduce the risk. Prostate cancer tends to more aggressive in African American’s and obese men.

2009 Estimated US Cancer Deaths*

Lung & bronchus Prostate Colon & rectum Pancreas Leukemia Liver & intrahepaticbile duct Esophagus Non-Hodgkin lymphoma Urinary bladder Kidney

30% 9% 9% 6% 4% 4% 4% 3% 3% 3%

Men 292,540

Women 269,800

26% 15% 9% 6% 5% 4% 3% 3% 2% 2%

Lung & bronchus Breast Colon & rectum Pancreas Ovary Leukemia Lymphoma Uterine corpus Multiple myeloma Brain/ONS

Prostate Lung & bronchus Colon & rectum Urinary bladder Melanoma of skin Non-Hodgkin lymphoma Kidney Oral cavity Leukemia Pancreas All  sites

25% 15% 10% 7% 5% 5% 5% 3% 3% 3% 100%

Men 766,130

Women 713,220

27% 14% 10% 6% 4% 4% 4% 3% 3% 3% 100%

Breast Lung & Bronchus Colon & rectum Uterine corpus Melanoma Lymphoma Thyroid Kidney Ovary Pancreas All  sites

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.
Source: American Cancer Society, 2009.

Currently most men are diagnosed with prostate cancer because of an elevation in the PSA blood test or an abnormality on the digital rectal exam. PSA (aka Prostate Specific Antigen) is a protein made by normal, as well as cancerous prostate cells. The primary function of PSA is to aid in fertility. Thus a very high level of PSA can be found in the ejaculate. Normally only a low level of PSA is detected in the blood, and elevated levels of PSA in the blood may be indicative of a problem. The most concerning cause of for an elevation in blood PSA levels (>2.5 ng/ml) is prostate cancer, but levels can also be elevated from non-cancerous conditions such as prostatic enlargement (BPH) and prostatic inflammation (prostatitis). Bike riding and sexual activity can also cause small transient elevations in blood PSA levels.

Ultrasound Guided Needle Biopsy of the Prostate

Factors that Help Determine the Most Appropriate Treatment

	Gleason Sum
	< 6 3 + 4 = 7 4 + 3 = 7 8 - 10	Low grade Low intermediate grade High intermediate grade High grade

Stage I

Tumor not detectable by imaging or clinical exam Low-grade tumor Less than 5% of tissue specimen

Cannot be felt T1a - cancer found in TURP specimen T1c - cancer found as a result of PSA elevation only

Stage II

Tumor not detectable by imaging or clinical exam - May be found in one or more lobes by neele biopsy Moderate/High grade tumor Less than 5% of tissue specimen

Can be felt during DRE (digital rectal exam) T2a - felt on one side of prostate T2b - felt on both sides of prostate

The expected risk of recurrence can be determined by a man’s staging information, Gleason score, and PSA level. The staging information refers to the result of the digital rectal exam. T1c means that the prostate feels benign (i.e. no nodules or firm areas) and T2 means that a nodule or rough area on the prostate is felt. The Gleason score is based on the pathologist determination of how cancerous cells found on the biopsy appear under the microscope.

Source: Based on Prostate Cancer Treatment Guidelines for Patients, Version III/October 2002, the American Cancer Society and National Comprehensive Cancer Network.

Source: Based on Prostate Cancer Treatment Guidelines for Patients, Version III/October 2002, the American Cancer Society and National Comprehensive Cancer Network.

Treatment Options for Clinically Localized Prostate Cancer

Early Diagnosis

• Surgery (Radical Prostatectomy)
  - Open Surgery (retropubic or perineal)
  - Conventional Laparoscopic Surgery
  - da Vinci™ Prostatectomy (robotic prostatectomy)
• Radiation Therapy
• Active Surveillance(watchful waiting)
• Cryosurgery (freezing prostate)
• HIFU

Radical prostatectomy involves surgical removal of the entire prostate and the attached seminal vesicles. A pelvic lymphadenectomy refers to sampling the lymph nodes in the pelvis at the time of radical prostatectomy. A lymph node dissection is typically performed in those men with high risk prostate cancer (ie. All GS 8 - 10, and GS 7 with PSA > 10 or all men with PSA > 20). Radical prostatectomy is recommended to treat localized prostate cancer in healthy men under age 70. The most common procedure, radical retropubic prostatectomy (RRP) is performed though an incision is made between the navel and the pubic bone or horizontally above the pubic bone (figure 1). In the radical perineal prostatectomy (figure 2), the prostate is removed through an incision between the scrotum and the anus (the perineum). Both procedures typically take between 2 and 3 hours. Patient undergoing RRP typically are asked to donate some of their blood before the procedure and stay in the hospital for 2 - 3 days. They also wear a foley catheter for 2 - 3 weeks post-operatively. The perineal approach is associated with less blood loss and patients typically stay in the hospital for 1 - 2 days. Patients after perineal prostatectomy typically wear a foley catheter for 7 - 10 days. Recovery from both procedures is typically 4 - 6 weeks. A lymph node dissection can only be performed through the retropubic approach so the perineal approach is not recommended for patients with high risk prostate cancer. Reports in the literature suggest that for most surgeons the perineal approach is associated with a higher risk for positive surgical margins (leaving cancer behind) than for RRP.

The side effects of RRP include impotence (inability to achieve erection) and urinary incontinence (leaking of urine). For men that are sexually potent prior to surgery, sparing one or both nerve bundles ("nerve-sparing") can preserve the ability to achieve erection.. Potent men younger than 65, undergoing nerve-sparing prostatectomy can preserve the ability to achieve erections 50 - 75% of the time, it may take 6 - 18 months for erectile function to recover. A nerve-sparing prostatectomy should only be performed in cases where it is likely that the cancer is contained within the prostate. For most surgeons, successful nerve sparing is more difficult to accomplish with the perineal approach.
The standard treatment options for erectile dysfunction can be used after RRP and may hasten return of normal sexual function. Mild to moderate urinary incontinence occurs in 10-20% of men after open prostatectomy and will usually improve in 3-6 months after surgery. Pelvic muscle exercises (Kegel exercises, biofeedback) can result in improved continence after surgery. The chance of severe, persistent urinary incontinence is 2-5% and can be corrected with surgical repair (artificial urinary sphincter).

After RRP, the prostate and lymph nodes are sent to a pathology lab for evaluation. If the lymph nodes and prostate margins (tissue around prostate) are free of cancer, the cancer is considered to be localized to the prostate and no further treatment is necessary. The prostate specific antigen (PSA) blood test should be undetectable after the procedure. If the lymph nodes or prostate margins contain cancer or the PSA remains measurable, further treatment (radiation or hormone therapy) may be required after surgery.

Robotic Prostatectomy

Robotic-Assisted Laparoscopic Prostatectomy (RALP)

The most recent significant advance in prostate cancer surgery is the adaptation of minimally invasive surgical techniques. In laparoscopic radical prostatectomy (LRP), five small incisions are made in the lower abdomen to allow the surgeon to introduce a camera and the specialized instruments used to perform the surgery. The operative field is magnified by the camera and viewed on a television monitor. The procedure is very similar to the radical retropubic prostatectomy (RRP) with removal of pelvic lymph nodes, prostate and seminal vesicles. The camera improves the visualization of the neurovascular bundles for the nerve sparing procedure. The better view of the urethra and bladder neck allows for a more watertight closure and faster removal of the catheter (7 days). Other advantages over RRP include less blood loss and pain, shorter hospital stay (usually one day), and faster recovery time. The major disadvantages of laparoscopic prostatectomy are related to the lack of 3-dimensional vision. LRP is extremely difficult to master and there are only a handful of surgeons in the world that are able to perform this operation safely. Even in the most experienced hands LRP may be associated with higher rates of positive surgical margins and risk for cancer recurrences.

The adaptation of a robotic surgical platform to laparoscopic prostatectomy has overcome most of the disadvantage of less-invasive prostatectomy by allow surgeons to operate in a 3-dimensional visual environment and to precisely control the surgical instrumentation. Robotic-assisted laparoscopic prostatectomy (RALP) using the da Vinci Surgical System is now by the far the most common surgical approach to prostate cancer surgery. The surgeon sits at a console near the operating table (figure 1) using small finger movements to precisely control the laparoscopic instruments that are connected to the robotic arms. The da Vinci robotic console enhances surgical vision by providing a better 3-dimensional magnified view of the surgical field. The surgical instruments are far more maneuverable when compared to RRP or LRP so that the robotic surgeons can be more precise than he could be with open or pure laparoscopic surgery.

Early results of RALP suggest that is associated with less blood loss, shorter hospitalization, less post-operative pain and earlier time to full recovery than for RRP or LRP. The vast majority of patients undergoing RALP, stay in the hospital for less than 24 hours and wear a urinary catheter for fewer than 8 days. The long-term outcome in regards to cancer cure remains to be seen, but early pathologic findings suggest that cures rate for RALP are comparable to those of RRP.

Goals for Open or Robotic Prostatectomy

External Beam Radiation Therapy

EBRT
IMRT (intensity modulated radiation therapy)
3DCRT (3-dimensional conformal radiotherapy)
IGRT (image guided radiation therapy)

External beam radiation therapy, or EBRT, has been used to treat prostate cancer for more than 50 years and has been traditionally the most common form of radiotherapy used for this disease.  EBRT is delivered daily, Monday through Friday, usually for 8 to 9 weeks.  EBRT may also be combined with seeds or HDR brachytherapy (discussed below) for certain cancer cases, usually as a 5-week course followed by seeds or HDR.  Each daily treatment session lasts for 5 to 10 minutes and causes no discomfort or immediate symptoms.  As the weeks of treatment go on, patients will experience usually moderate bladder and rectal symptoms - increased trips to the bathroom, some difficulty passing urine, and occasional urinary burning, among others.  These acutesymptoms typically subside after a few weeks following the end of treatment.  The most common long-term side effects of EBRT are bladder and rectal urgency as well as erectile dysfunction.

In recent years, this treatment has been greatly improved with such technical advances as IMRT and IGRT.  IMRT, or intensity modulated radiation therapy, is the most complex form of external radiotherapy today.  This technology creates a field of radiation that is tailored to the size and shape of the patient's tumor and greatly reduces radiation exposure to the surrounding normal organs (rectum and bladder).  An older version of this technology is called 3DCRT, or 3-dimensional conformal radiotherapy, and is still mentioned in some older patient books.  IGRT, or image guided radiation therapy, is used together with IMRT to help deliver radiation accurately to the prostate.  IGRT first involves placement of non-radioactive "seeds" into the prostate before treatment begins.  When the patient arrives for his daily treatment, a quick x-ray is taken of these seeds to help determine the exact location of the prostate in the body.  This information is then used to setup the patient as precisely as possible to assure accurate radiation delivery. These new technologies allow for the delivery of higher curative dosages of radiation to the prostate without increasing the risk for side effects and complications.

Brachytherapy

iodine seeds
palladium seeds
LDR (low-dose rate) brachytherapy

Radioactive seeds have been used to treat prostate cancer for 25 years and offer another conventional therapy for this disease.  The 2 most commonly used seeds are iodine (I-125) and palladium (Pd-103).  Each type of seed has different radioactive properties, but neither has any proven clinical advantage over the other.  Placement of seeds is performed in an operating room, ideally with both your urologist and radiation oncologist present.  Both your doctors combine their expert skills to perform the procedure - your urologist is skilled at handling surgical instruments, and your radiation oncologist is trained in radiation physics to determine where the seeds need to placed in the prostate.  The seeds are loaded into long, thin needles, and the needles are then passed through the skin between the rectum and scrotum and into the prostate.  As the needles are removed, the seeds are deposited within the prostate.  The procedure takes about an hour and does not usually require an overnight stay.

Seeds are commonly used alone for low-risk cancers and are combined with a 5-week course of external radiotherapy for higher-risk cancers.  Side effects include urinary frequency, urgency, burning, and poor flow and are usually more severe and longer lasting than side effects following external radiotherapy.  Other risks include spontaneous dislodging of seeds from the prostate and migration of dislodged seeds to the lung or heart.

Patients with a large prostate, history of TURP (transurethral resection of prostate), or other significant medical problems are not good candidates for a seed implant procedure and are offered other treatment options instead.

HDR Brachytherapy

high dose rate brachytherapy"
smart seed" brachytherapy
iridium seeds

HDR brachytherapy is a more sophisticated and controlled way of delivering seed radiation to the prostate.  This technique involves placing thin, hollow catheters into the prostate in the operating room followed by transfer of the patient to the radiation oncology office.  The catheters are then connected to a small machine that transports an HDR radiation seed in and out of each implanted catheter.  The seed treatment takes a total of about 15 minutes.  At the end of the treatment, the catheters are disconnected from the machine and are removed from the prostate.  Typically, the patient is brought back for a second, similar procedure a few weeks later to complete the brachytherapy treatment.

HDR brachytherapy offers important advantages over permanently implanted seeds.  HDR technology allows your radiation oncologist to control - very precisely - how much radiation is delivered to the prostate by adjusting the position and time the HDR seed travels through each prostate catheter.  Likewise, your radiation oncologist also has greater control over limiting radiation exposure of the bladder and rectum to reduce side effects to these healthy organs.  And, because no seeds are permanently implanted in the prostate with HDR, there is no possibility of seeds migrating to the lungs or heart as with older brachytherapy techniques.

HDR has been used for 20 years to treat prostate cancer and is considered a standard choice for therapy.  Commonly, HDR is combined with 5 weeks of external radiotherapy, although HDR alone is currently being investigated as a treatment option for low risk cancers.  Results with HDR have been generally excellent with high cure rates and low complication rates.

Radiosurgery

SBRT (stereotactic body radiation therapy)Cyberknife
Trilogy

Radiosurgery is a new, investigational technology in the treatment of prostate cancer.  21^st Century Oncology is currently conducting a study of prostate radiosurgery and is one of the few centers in the world that has published results on patients treated with this "cutting-edge" form of radiotherapy.

Radiosurgery is not surgery but instead uses an extremely precise, "scalpel-like" radiation beam that sharply targets the prostate gland for high-dose treatment.  The potential advantage of this treatment is improved protection of the bladder and rectum from radiation exposure while delivering a high radiation dose to the prostate.  With this additional precision, larger radiation doses per treatment may be safely delivered than with conventional external radiotherapy - as a result, the total time for treatment may be reduced from 8 - 9 weeks to 1 - 2 weeks.  Radiosurgery may also be combined with conventional EBRT for certain cases.

Results with radiosurgery have been very favorable to date with few, modest complications.  Our patients have generally reported increased urinary frequency and urgency and increased bowel movements.  These symptoms usually resolve within a month.  While we are encouraged by these early favorable results and are pleased to be the early experts in this "cutting-edge" technology, we are careful to explain to our patients that long-term cure rates are not yet available as prostate radiosurgery was first performed in 2003.

Proton Radiation Therapy

Proton radiotherapy is an external form of radiation and has been available for prostate cancer treatment for 30 years.  Proton therapy differs from other forms of external radiotherapy in that protons - tiny subatomic particles - are used to deliver radiation to the prostate instead of x-rays.  As a protons enter the body, these particles give off some radiation to the tissues and organs along their pathway to the prostate.  Once the protons reach the prostate, they then give off a much higher dose of radiation and stop.  Beyond the prostate, there is little-to-no radiation produced by protons.  A typical schedule of proton treatments and dosages are the same as for IMRT - usually daily treatment, Monday through Friday, over 8 - 9 weeks.

Because similar radiation doses are delivered as for IMRT, prostate cancer cure rates are not expected to improve with protons.  The hope behind this technology is that protons may perhaps be a more precise way of delivering radiation to the prostate and may therefore better spare surrounding normal organs from radiation exposure and reduce side effects.  However, this reduction in side effects has not yet been proven true.  In fact, the single study comparing protons to x-rays reported by Harvard stated a higher rate of rectal and urinary side effects with protons.  We hypothesize the reason for this finding is that protons, while theoretically precise, may behave less predictably or be less forgiving in the body than x-rays when treating an actual patient, resulting in unintended complications.

Options for men with more advanced cancer and high risk of recurrence may include hormonal therapy, hormonal therapy plus radiation, or radical prostatectomy and lymphadenectomy followed by radiation.

Treatment Options for Cancer that Returns or Continues Grows after Treatment

The treatment that is most appropriate for a man’s recurrent prostate cancer depends upon where in the body the recurrence occurs and if it has responded to hormone therapy. Treatment options may include active surveillance, radiation therapy (for patients with failure after radical prostatectomy, radical prostatectomy (for patients with failure after radiation therapy) and hormonal therapy.

Prostate Cancer Nomograms