What is the Prostate?

The prostate (not "prostrate") is a gland, normally the size of a walnut, that is found in the male pelvis. It is located directly under the bladder, and surrounds a portion of the tube draining the bladder, called the "urethra". It is right in front of the lower rectum, and thus can be felt ("palpated") with an examining finger("digital exam") inserted into the rectum. The prostate has 5 distinct portions, or"lobes", including "anterior" and "median", but the examining finger palpates only the "posterior" lobe and right and left "lateral" lobes. The prostate manufactures "prostatic fluid", a clear high-sugar substance, which mixes with semen to activate it. Coming off the prostate are two "wing-shaped" sacs, called"seminal vesicles", which store semen for injection into the urethra, to be mixed with prostatic fluid, during ejaculation. The prostate is surrounded by a tough, fibrous "capsule." It is fed blood by pelvic arteries ("internal iliac") and it drains to similarly named veins. A network of"lymphatic channels" run through and around the prostate, collecting blood serum to purify it. These channels lead to "lymph nodes" which are glands filled with White Blood Cells that filter the blood, destroying germs. The lymph nodes are named as groups, and connected to each other so that their filtrate can eventually be returned to the bloodstream. Lymph channels can act as conduits for spread of infections or cancers, and usually swell when they capture these. Pelvic Lymph node groups pertinent to the prostate include the peri-prostatic, obturator, hypogastic, sacral and common iliac "nodes." Once prostate cancer or infection has gone to local lymph nodes, it is not longer considered to be confined to the prostate (but may still be confined to the pelvis).A bundle of nerves ("neurovascular bundle") lies in the pelvis on either side of the prostate. If these area are damaged, it will impair a man's ability to get an erection and ejaculate, possibly causing complete impotence.

The prostate tends to swell in size as a man ages; this is called "Benign Prostatic
Hypertrophy" or"BPH" for short. The enlarged prostate may press upon the urethra and restrict urine outflow from the bladder, causing small frequent urinations ("frequency"), dribbling urine, and incomplete bladder emptying ("post- void residual"). Medications like Prescore and Hytrin may help alleviate these problems without surgery. If medications fail, a "Tans Urethral Resection of Prostate"("TARP") may be done to chip away the swollen prostate tissue and decompress the urethra, to reestablish easy urination. The prostate may become infected ("prostatitis") or develop calcium "stones" which lead to BPH type symptoms, or develop frank cancer . However, any prostate problem is rare in a man younger than 50 years old.

What is Prostate Cancer?

The prostate is made up of many individual cells, which work together in harmony. Normally these cells divide quickly to make new cells, and grow the prostate, in womb life, early childhood, and through male puberty. In adulthood, the cells only divide to replace those lost to injury, disease or old age. The division of cells to produce new ones is under tight control by the "genes" within each cell. These genes are made up of "DNA", and if it becomes damaged, the cell may start dividing out of control.Prostate cancer starts in a single cell which has become abnormal. This cells produces millions, and eventually billions, of copies of itself. The copies are called"clones." These clones fail to function as normal prostate tissue, but instead divert resources from healthy cells to fuel their own growth. When there are about 1 billion cells, they form a clump, or "tumor" 1/2 inch across. A "tumor" merely means a swelling, it can be caused by infection, inflammation, cancer or whatever. If a tumor only grows in it's local area (even very large) but does not have the capacity to spread to distant body areas, it is called"benign" and is not cancer. If, however, the tumor has the ability to spread to distant body areas, it is called "malignant" and this is cancer. The actual process of spread is called"metastasis", and can occur to any area of the body. This is what makes cancer so dangerous.

How Common is Prostate Cancer?

Prostate cancer is the most common cancer in men, in the U.S.A, with 317,000 new cases in 1996 . It is the second leading cause of cancer death in men, killing about 35,000 men per year in the U.S.A. Although the deadliness of certain prostate cancers is obvious, it is also important to note that only about 5% of men with prostate cancer actually die from it, instead dying with it . Most often, some other "co-morbid" condition like heart attack or lung cancer kills the patient long before prostate cancer would. As many as 80% of men over age 80 years can be shown to have some trace of cancer in their prostates! The average patient is 65 years old at time of detection. The aggressiveness of prostate cancer is variable, and each man must understand the nature of his particular disease to make wise decisions about it. In general, Black men get prostate cancer more often than White men in the U.S.A, but Blacks in Africa have a low risk. Asian men have a low risk of prostate cancer.

What Causes, or Increases the Risk for Prostate Cancer?

As for all cancers, the exact reason why one man gets prostate cancer and another does not remains unknown . However, there are some associations, called "risk factors", that seem to increase the chances a man will develop it in the U.S.A:

1) Male Sex (since only males have a prostate), Black, older than age 60.
2) Family History of prostate cancer in father or uncles.
3) Multiple Sex Partners, a transmitted virus may be a factor.
4) High Testosterone Levels, the "sex hormone" is low in Asians, high in Blacks!
5) Benign Prostatic Hypertrophy increases risk 4 times (or chance of detection?).
6) Exposure to high dietary fat, cadmium metal.

Cigarettes and Alcohol do not increase the risk for getting prostate cancer.

Is Prostate Cancer Preventable?

Having only one sex partner and lowering dietary fat may help. Also, having one's testicles cut off ("bilateral orchiectomy") at a young age will reduce the risk to nearly zero (eunuchs don't get it) but this is not advised. The truth is, there isn't much you can do to prevent prostate cancer; the key is to recognize it's existence and characteristics early.

What are the Symptoms of Prostate Cancer?

As with any cancer, very early prostate cancer produces no symptoms, since the "tumor burden" is too small to cause interference with normal body functioning. It is most commonly detected symptom less ("asymptomatic") by a screening blood test called "Prostate Specific Antigen" or "PSA" for short. The prostate normally produces this enzyme and releases it into the bloodstream; it's level increases with BPH, infection, cancer or even vigorous rectal exam. However, in cancer the PSA is usually markedly increased (when adjusted for the volume of prostate tissue), compared to smaller increases with other conditions. A PSA reading of over 4.0 milligrams per milliliter of blood starts getting suspicious for prostate cancer, since 95% of men under age 50 will be below this number. A PSA reading of 30 mg/ml or over almost certainly indicates cancer (technical note-- In general, the PSA increases by 3 mg/ml for each gram of cancerous tissue). It is possible to see PSA's in the thousands when the cancer is widespread.

If and when prostate cancer actually produces symptoms, they are most likely to resemble those of BPH-- a swollen prostate causing urinary frequency, especially at night ("nocturia") along with incomplete emptying of the bladder ("post-void residual"). Symptoms of more advanced prostate cancer include pain in the pelvis (from the cancer invading nerves), impotence (ditto), swelling of the legs or genitalia (from blockage of lymphatic flow by tumor) or even complete shutdown of urine output ("uremia") which causing itching ("pruritis") and blurred thinking ("uremic encephalopathy"). The first symptoms noted may even be from cancer spread to other organs, with bone pain, weight loss, fatigue and low blood counts ("anemia"). The most common area for spread to bone is the pelvis and spine, spread to the finger or toe areas is rare. Spread to the brain may occur in advanced disease and produce neurologic symptoms of poor judgment, partial paralysis, sensory loss, and seizures. Spread to spinal cord may cause weakness and numbness requiring immediate therapy to prevent irreversible paralysis. Fortunately, most of the symptoms of prostate cancer can be alleviated (see section on "palliation" ).

How is Prostate Cancer Detected and Evaluated?

Today, the most common way of detecting Prostate Cancer is through the PSA test (Hospitals often run free screening programs, hoping to treat you if they detect cancer). Another common way the disease comes to attention is during an annual physical exam when the doctor does a"digital rectal examination" and feels a lumpy ("nodular") or diffusely enlarged prostate gland. The gloved examining finger is then applied to a specially treated card and "developer" placed on it ("guiac test") to look for occult (too little to be seen with the naked eye) blood in the rectum. If there is suspicion of prostate cancer, a PSA test will be ordered, and the patient usually sent to a "urologist." A urologist is a surgeon who specializes in operating on the urinary tract, and treating all sorts of "genito-urinary" diseases.

The value of the PSA will be noted by the urologist, who then performs a "Tans- Rectal Ultrasound" ("THUS") which detects abnormal areas in the prostate by checking how sound waves bounce back off of them to a detector. For THUS, a probe is merely inserted into the rectum and information gathered. Then the urologist inserts a "biopsy gun" into the patient's rectum and removes tissue samples from suspicious areas in the prostate gland. This can be done with local anesthesia. Many samples may be taken, and at least both the right and left lobes are sampled. The urologist then send the biopsy samples to a"pathologist." A pathologist is a physician who specializes in diagnosing disease from tissue samples.

The pathologist determines if cancer is present by examining the biopsy materials by slicing them into thin sections, staining them, and examining them under the microscope. Specifically, (s)he looks to see how the prostate cells try to form glands, and what the individual cells look like. If there are too many glands, too small and too close together, this is prostate cancer. If the cells are dark and ominous looking, and have frequent divisions, then this tends to be a more aggressive breed of prostate cancer. On the other hand, cells which closely resemble normal prostate tissue tend to behave less aggressively ("indolently").

A pathologist named Gleason developed a scoring system for prostate cancer, in wide use today. This system assigns a number grade, 1 through 5, to each of two representative areas of prostate tissue. A score of 1 means the cells look very benign, and 5 means they look maximally cancerous. The sum of the two areas is taken as the"Gleason Score", which ranges from 2 through 10. In general, scores of:

2 - 4 means "well differentiated", "low grade", or "indolent" cancer
5- 7 means "moderately differentiated" or "intermediate behavior"
8 - 10 means "poorly differentiated", "high grade" or "aggressive" cancer.

It is not uncommon to have more than one cancer score for a given patient, for instance a Gleason score of 5 in the right lobe of the prostate, and 7 in the left lobe. Each biopsy specimen the urologist takes will have been labeled as to it's origin, and will be separately analyzed by the pathologist. It takes several days for the report to be completed and released back to the urologist. The PSA usually increases with the aggressiveness (as well as size) of the cancer, except for very aggressive, poorly differentiated cancers which may not synthesize as much PSA. The pathologist may take the PSA data into consideration in qualifying the type of cancer. Practically all (over 95%) of prostate cancer is "Adenocarcinoma", meaning it arises from glandular tissue. Rare types, like"lymphoma" and"sarcoma", are separate topics.

If prostate cancer is confirmed, the urologist will do further evaluation to determine how extensive the disease is. These may include:

Blood and Urine Tests are standard pre-operative ones to assess general health. Routine tests include Complete Blood Count("CBC") to look for anemia and infection. A Blood Chemistry Panel ("SMA") measures sodium, potassium, blood sugar, cholesterol and liver and kidney function. It also measures an enzyme called"alkaline phosphatase" which can indicate bone invasion by a cancer. An older but still used blood test for prostate cancer is "Prostatic Acid Phosphatase" or"PAP." It is not as specific a"tumor marker" as PSA, but is helpful for confirmations. A more recently developed test is"red blood cell ("erythrocyte") PSA", which helps determine if the cancer is localized, or has spread into the bloodstream. If some time has elapsed since the initial PSA test (at least a month) a repeat PSA may be ordered to see how quickly it is increasing. This is called the"PSA velocity" and is an important indicator for how aggressive the cancer is. Since PSA normally is elevated with even benign enlargement, it is helpful to adjust it for the size of the gland (as mead urea by Ultrasound or CT Scan). This is accomplished by simply dividing the PSA by total prostate size, and is called"PSA density." This "density" will ordinarily be less with benign enlargement ("Hypertrophy") than prostate cancer. If a pelvic surgery is contemplated, blood tests for clotting ability (PT, PTT and bleeding time ) are standard. A Urinalysis (UA) to check for protein, blood or infection completes the lab tests.

Radiologic Tests include Standard Chest X-Ray to look for signs of infection or lung tumor, and a CT - Scan of the pelvis to measure total prostate size, look for capsule penetration by the tumor, and check the size of pelvic lymph nodes. The CT scan is more accurate when a "contrast" injection is given through an arm vein, which highlights blood vessels. If a"CT with Contrast" is ordered, insist on "omnipaque" brand or equivalent contrast, it is more expensive but more comfortable to get and less likely to cause an allergic reaction. The pelvic area lymph nodes are normally pea-shaped and no larger than 1 cm. (about 1/2 inch) each; they will enlarge when invaded by infection or cancer. The CT scan is only 70% accurate at detecting cancerous lymph nodes. Another excellent (but high cost) test for looking at the pelvis is "Magnetic Resonance Imaging" or "MRI" especially with a special "prostate coil" to enhance it's resolution. The MRI uses magnetism instead of radiation, and can help tell the extent of tumor in the pelvis. A different type of contrast agent, called "gadolinium", may be used with an MRI. If a patient comes in with frank urinary tract obstruction, an "Intravenous Pillowgram" ("IMP") will be ordered. For this test, some contrast is injected into an arm vein and X-rays of the pelvis are taken as the contrast is excreted out through the kidneys. It tells where an obstruction is located, and if the kidneys have become damaged from urine back-pressure ("hydronephrosis").

A Bone Scan is an important and usually obtained test,, especially if the PSA level is above 10 (mg/ml). If the PSA test is less than 10, there is less than a 5% chance the Bone Scan will show bone involvement, but many doctors like to get a "baseline" Bone Scan anyway for later comparison. A Bone Scan is performed by injecting some radioactive tracer into an arm vein, waiting for it to get untaken to Bone (which the tracer has a special affinity for) and taking some special X-rays that pick up the radiation given off by the tracer. It takes a few hours, and isn't painful. Any area of bone where the metabolism is increased will take up the tracer (Technicium- 99) including areas of cancer, recent fracture, or infection. If areas on the Bone Scan are positive ("light up") the radiologist will attempt to say whether or not they are probably cancerous, by noticing fine details in the manner in which the tracer is taken up in the suspicious area. If there are many positive areas and the PSA is very high (hundreds or thousands) then there is no question that if the Bone Scan shows characteristic uptake for prostate cancer (i.e. mostly in the pelvis and spine) this is cancer spread.

The scan may be so positive that almost the Bone Scan "lights up" from diffuse cancer spread to bone. This is called a"superscan" and is seen in the final stages of prostate cancer. If, however, the Bone Scan just shows one or two suspicious areas, only an actual biopsy of the area will tell whether this is cancer, as opposed to an unrecalled injury or benign bone cyst. Plain X-rays of the area may help, some cancers show areas of intense new bone formation around them ("elastic") while some cancers show bone destruction ("lyric"). Prostate cancer usually shows as lyric bone lesions. There is a lot of pressure on radiologists to confidently state whether an abnormality on Bone Scan is cancer or not. New technology using "PET" scans (for"Positron Emission Tomography") may help distinguish whether the area is cancer. If the cancer has spread to bone, it has important treatment ramifications, most pointedly making radical prostatectomy useless, as seen in the "treatment" section.

An area of important concern for treatment is whether the lymph nodes in the pelvis show cancer (are "positive") or not. Thus, once cancer is confirmed by the pathologist, and if the other lab work and Bone Scan are acceptable for surgery, the lymph node"status" (i.e. involved or not) must be determined as part of the "staging workup". A common test used to be"lymphangiography" where dye is fed up through some small foot veins on both legs, it migrates up to lymph nodes in the pelvis, and pelvic X-rays are taken. The pattern of the dye on X-ray would show if the lymph nodes were (noticeably) involved. Some doctors still do this test, by very few are left who are proficient at it. It is not recommended (outside a research setting with full patient consent) since: It is hard to do well and interpret, it misses some of the the main lymph nodes in the pelvis (internal iliac and obturators), it is uncomfortable and may lead to blood clots in the legs, and finally it doesn't tell if a lymph node is involved with cancer too small to see on X-ray. The main lymph node test urologists do today is the "staging lymphadenectomy" -- that is surgically removing some pelvic lymph nodes and sending them for microscopic analysis by a pathologist looking for cancer.

The urologist usually takes from 5 to 15 lymph nodes on each side of the pelvis, by inserting his "laparoscope" up through a groin incision. The test is usually negative (allowing the urologist to proceed with surgery if this is the option chosen ). It leaves some soreness in the area for a week or so, and patients heal from this before any further surgery is done. The "staging lymphadenectomy" is NOT considered a therapeutic procedure, merely a diagnostic one.

How Does Prostate Cancer Spread?

As mentioned prostate cancer starts in a single cell . However, several cells may become simultaneously involved with cancer-- in one study the disease started in more than one prostate area in 77% of patients! The cancerous cells grow to form a hard tumor, which may then erode through the capsule of the prostate, or up into the seminal vesicles. From there, cancer cells commonly get into lymphatic channels and go to lymph nodes in the pelvis. Cells can also get into the bloodstream and travel to distant organs, forming metastatic tumors there. The areas or distant spread, in order, are lymph nodes, bone, liver lung and brain. The tumor may press on the spinal cord ("epidural spinal cord compression") which is a medical emergency to prevent irreversible paralysis. Also, the original location ("primary tumor") in the prostate may grow quite large, blocking off urination and causing pelvic pain. The cancer can go to bone marrow causing anemia, infection and debility-- the most common causes of demise in advanced prostate cancer.

How Is the Extent of Prostate Cancer Gauged?

Like all cancers, the extent of prostate cancer is given by the"stage." There are two staging systems in wide use, the older "Jewitt" (A - D) and newer"AJCC" (American Joint Cancer Committee) system (I - IV):

Stage I or "A" means the cancer is not clinically detectable with a digital rectal examination and is usually picked up by a PSA test only (Ic) .
Stage II or "B" means the cancer is physically detected on rectal exam (can be felt "clinically") in either one lobe ("B1") or both lobes("B2") .
Stage III or "C" means that the cancer has either penetrated the prostate's capsule, invades the seminal vesicles, or both.
Stage IV or "D" means the cancer invades the bladder or rectum, or has spread to the lymph glands("D1") or to distant organs("D2") .

What are the Factors that Determine a Patient's Outcome?

While we cannot say how long any particular cancer patient will survive or how well they will fare, we can look at groups of patients for this data, and see what factors seem to contribute to doing better or worse. These are called "prognostic factors" :

Stage - The more advanced the cancer is, the more poorly patients tend to
do. Five and Ten year disease-free survivals by stage are given below.
Grade - Poorly differentiated (high Gleason Score) worse than well differentiated (low Gleason Score).
Age - Younger than 55 years old when first diagnosed is worse.
Race - Black men present with higher stage and higher grade cancers, on average, than White men. Overall, Black men do worse than White men. 5) PSA-- Higher PSA is worse; either before or after therapy. Patients with a PSA of over 50 when first diagnosed have a 90% chance of spread to seminal vesicles and 66% chance of positive lymph nodes. Failure to achieve a normal PSA one year after therapy means less than 70% chance of cure.
PAP - If elevated more than 25% over normal, these patients do worse.
Lymph Nodes - Some studies show patients doing just as well with one lymph node involved, but much worse if multiple lymph nodes in the pelvis are involved. Other studies have shown no affect of lymph nodes on survival for stage "B" disease, but a dramatic decrease in survival when lymph nodes are positive for stage "C" disease. Lymph nodes involved in the abdomen ("paraaortic") is worse than only involvement in the pelvis.
DNA - If the prostate cancer cells have an odd number of gene copies (called "aneuploid") as opposed to the normal number ("diploid"), it is worse.
TURP - Patients that have gotten a resection to remove bulky prostate tissue blocking urinary outflow may have cancer cells detected in the tissue removed. These patients tend to do worse since they usually have more bulky, advanced disease. There is evidence that having a TURP may help spread cancer cells into the bloodstream, so it is not currently recommended as initial treatment for prostate cancer.
Co-morbid Factors - means the general condition of the patient; their ability to tolerate aggressive treatment. People in better shape tend to do better.

How Curable is Prostate Cancer?

This depends upon the above factors, and the treatment selected. Overall, the textbook survivals, by stage, with conventional treatment are:

It is important to remember that the above results are for survival from all causes, including heart attack, accidents or other cancers. Patients with prostate cancer tend to be older and have other serious medical conditions. Also, these numbers are "Disease-Free Survivals", meaning that no prostate cancer can be detected. Recall that only 5% of patients with prostate cancer die from this disease; some other problem commonly kills them first. Thus, many patients live high-quality lives for many years with prostate cancer, simply by treating symptoms as they arise.

What is the Conventional Treatment for Prostate Cancer?

The classical, and still used, treatments for prostate cancer include:

1) Observation-- Doing Nothing but following the Cancer's Growth.
2) Surgery -- The Classical Operation called "Radical Prostatectomy".
3) Radiation Therapy-- Either "External Beam", "Interstitial", or both.
4) Hormonal Therapy-- Chemicals influencing cancer to shrink (or not grow). These therapies may be combined together, as seen in the "Latest Effective Treatment" section. We will now discuss each of them in detail:

Observation at first sounds unrealistic-- after all, what's the point of watching a cancer get larger, possibly beyond the point of successful treatment? All cancers do tend to grow, over time, and the longer they grow, the more chance they have to spread and ultimately kill the patient. For cancer to "disappear" on it's own has been observed, but it is exceedingly rare. So why take a chance on mere observation?

The answer is owing to the rarity with which prostate cancer actually kills . There is no reason to subject someone to toxic and dangerous treatment which is worse than the disease. In cancer, it has been well known for decades that the treatment may be worse than the disease. Most everyone can recount some horror story of a cancer patient who was "burned" or "poisoned" to death by their cancer doctor. Look at these facts, from a classic Swedish study:

• Prostate Cancer typically afflicts the elderly (80% of of men 80 years old!)
• These patients often have other "co-morbid" conditions limiting life expectancy.
• Therapeutic options (such as surgery) may be restricted for some patients.
• We live in an era of shrinking and more expensive medical resources.
• Prostate Cancer is now typically found (via PSA) at "sub-clinical" stages.
• After 5 years of observation, only 20% of patients have local progression.
• After 5 years of observation, less than 10% develop distant metastasis.
• The total progression rate with observation alone at 5 years is less than 30%
• The average death rate from prostate cancer in all studies is less than 5%.

Results of Observation

It has been concluded by the Patterns of Care Studies in the U.S.A. that observation is a viable alternative for well differentiated stage "A" (I) prostate cancer, especially in patients over 65 years old. For patients in good general health who are younger or who have more aggressive disease, some therapy is appropriate, since this is the subgroup who may actually die of their prostate cancer if left untreated.

Surgery for Prostate Cancer has been done since 1905 for cancer detected by the rectal examination. Since urologists are trained as surgeons, this is the procedure of choice (if the patient is a good surgical risk) for localized (stages "A" and"B" ) prostate cancer--"A chance to cut, a chance to cure" is the surgeons motto. The classic operation is called"Radical Prostatectomy" and is typically done after doing a"staging lymphadenectomy" to check that disease doesn't involve lymph nodes.

The Radical Prostatectomy operation involves placing the patient under general anesthesia and making an incision above the pubic bone. Today this "retropubic" approach is used, as distinct from the older "perineal" approach between the scrotum and anus. There is better ability to visualize and remove lymph nodes with the current approach. The ENTIRE prostate gland is removed, along with the seminal vesicles and a portion of the bladder neck. Classical prostatectomies used to sever the neurovascular bundles that enter at the sides of the prostate capsule, causing 100% impotence. New approaches have decreased the impotence risk. The patient spends several days in the hospital after surgery, and healing is 75% complete at three weeks. At this time, the patient can once again lift heavy objects.

The main problem of this operation, besides impotence, was finding more advanced tumor at operation than originally thought. This is very important, for it means that the "curative" surgery attempt has failed, and another therapy (i.e. radiation therapy and/or hormones) will now be necessary.In fact, this "upstaging" occurs in up to 70% of patients getting surgery! Specifically, studies have found that 10% of clinical "stage A," 35% of "stage B1" and 70% of "stage B2" are actually "Stage C" at surgery . This means, by definition, that tumor is being left behind, for "Stage C" (or "D") patients are NOT candidates for surgery. Once the cancer has invaded the capsule, or up into the seminal vesicles, it cannot be fully removed with any currently responsible surgery. It has been generally accepted that:

10% of new cases are stage "A" or "I"
20% of new cases are stage "B" or "II"
40% of new cases are stage "C" or "III"
30% of new cases are stage "D" or "IV"

However, when patients get surgery for stages "A" and "B", we see that they are often actually stage "C"! In fact, perhaps 70% of new patients are actually stage "C," but we don't have the technology to prove it without opening them up to take a look! This important fact must be considered before agreeing to surgery-- There is an excellent chance that the patient will need further therapy. This can either be obvious at surgery, when the pathologist says that the capsule has been penetrated, or in the ensuing months when the patients PSA begins to rise again. The most common therapy after surgery is Radiation, to be discussed. The above data also mean that survival results for Radiation may not accurately reflect how advanced the disease is in only Irradiated patients-- We give a survival for stage "B", as was thought by clinical exam, but the patient may actually be Stage "C"-- thus, stage for stage, Radiation may work better than the "by stage" survivals suggest. Remember, the surgeon has the advantage of actually seeing the stage (s)he is working with.

An important advance in surgery was made by Dr. Walsh at Washington University in St. Louis-- his modification is called a"Nerve Sparing Prostatectomy." This means that the "neurovascular bundles" entering the sides of of the prostate is spared; results appear equivalent to the classic operation but impotency is reduced to 50% or less (similar to Radiation Therapy). Since the operation is relatively new, no 10 year survival results are yet available. However, Dr. Walsh's technique is now available at many University Academic Urology Departments. Still, any technique still suffers from the fact that so many patients are found to need more therapy after surgery, thus getting the side effects of more than one therapy.

"How Curable is Prostate Cancer?"

Radiation Therapy has been used for at least 6 decades for prostate cancer, initially for those unable to tolerate surgery, or whose cancer was obviously too large to remove by operation. It was discovered in the course of time that survivals of patients radiated for early prostate cancer appeared identical to those of surgery, and this was borne out in a famous National Institute of Health Conference in 1987: "For localized prostate cancer (i.e. stages "A" and "B") no difference in survival has been seen between Radiation Therapy and Radical Prostatectomy"

Furthermore, for locally advanced prostate cancer, Radiation Therapy is the standard treatment of choice. Surgery should not be proposed for these patients, because the majority are found to have more disease at surgery ("pathologically upstaged") and long-term survival with surgery alone is poor. There has never been a balanced study comparing, head to head, radiation therapy to surgery for early disease, since again we need to open up the patients surgically to accurately stage them.

Radiation Treatments are administered under the supervision of a "Radiation Oncologist" -- a cancer doctor who specialized in using radiation. There are 2 basic types of Radiation Therapy-- "External Beam" and "Interstitial Brachytherapy." The most commonly given type, over the past 50 years, has been External Beam, where a ray of high energy photons is aimed at the pelvis from several angles to uniformly irradiate the prostate area. On the other hand, "Interstitial Brachytherapy" involves actually placing radioactive needles through the perineum (the area between the scrotum and anus") and into the prostate tissue. Both types of treatment may be used for a given patient.

Radiation kills cancer cells by damaging their DNA, they die when they try to divide. Thus, damaged cancer cells die even after the treatment is complete. Radiation will also kill normal cells, which limits the amount that can be given. However, it usually takes more radiation to kill normal cells than cancer cells, and normal cells can often repair the radiation damage, while cancer cell can not. Nevertheless, it is important to be exacting as possible in the administration and dose of radiation, so as to minimize the injury to adjacent normal cells.

To receive therapy, a patient is first seen in"consult" by a radiation oncologist, who reviews the patient's medical record, complaints, and radiology films. After explaining the possible benefits and side-effects of radiation, the patient is scheduled for a "simulation." This means the area to be treated is marked out on a replica treatment machine, and films are taken. Some barium contrast material is usually squirted up the patient's rectum, and other contrast may be placed into the penis opening ("urethra") to determine the lowest portion of the prostate ("urethrogram"). Watercolor marks are painted on the patient to denote the treatment area, and eventually small, permanent tattoos are placed on the skin. Sometimes the patient is sent for a CT scan along with the simulation, the whole process takes less than 2 hours, and is painless. Information from the simulation and relevant scans is placed into a "treatment planning computer", which generates a"plan." This plan tells how much radiation is going to the tumor area, and how much to adjoining normal tissues. For prostate cancer, particular attention is paid for how much radiation is going to the bladder, rectum, and small intestine. Normally, the beam is aimed from 4 directions (front, back, right and left sides) to uniformly dose the prostate. Higher energy treatment machines (over 15 Megavolts) also help smooth out the dose to the prostate. The plan is reviewed by the radiation oncologist and also by a specially licensed Radiation Physicist prior to starting therapy.

The patient then comes in for their "treatment start." They are placed on a hard, flat table in a specially shielded room and aligned with laser lights. The actual treatments are given by "Radiation Therapists", or "R.T.T's", who are first certified for diagnostic X-rays and then get additional training to deliver therapy. For the first treatment, "verification films" are taken to ensure proper positioning; they do not tell anything about the cancer. The actual treatment only takes a couple of minutes and is given with a Linear Accelerator (or occasionally older Cobalt-60) which precisely aims a beam of photons at the treatment area. The head of the machine can swivel about the patient, to give the treatment from different angles. The patient needs only to lie still. Areas that are not to be treated can be "blocked" with special lead-type blocks in the head of the treatment machine. Normally, patients area treated 5 days a week, Monday through Friday, taking only several minutes each day. The usual dose for prostate cancer is 66 Gray (units of radiation) given at 10 Gray per week. If a treatment is missed, it is simply tacked on to the end so full prescribed dose it given. It is common to "cone down" off of the full pelvis after 50 Gray (since this is the tolerance dose for the small bowel) and shrink the field to treat the prostate proper only. This is called a "boost". Be aware that treatment normally covers the major lymph nodes in the pelvis.

Radiation to the pelvis area is painless, the patient does not become "radioactive", nauseated or lose their scalp hair. The patient can usually maintain normal activities, such as working, driving, and intake of alcoholic beverages. The side-effects of External Beam treatments are classified as "acute" (during treatment) or "late" (months to years after treatment). The most common acute symptoms are reddening of the skin in the treatment area, and anal area irritation. After several weeks of radiation therapy, it is common to develop frequent urination and diarrhea as the bladder and rectum (respectively) become irritated. Prescription of soothing steroid suppositories and anti-diarrheal medicine is usually all that's necessary to treat these acute effects; some dietary modification (less fruit and fiber) may also help. There is often a sense of greater fatigue while receiving radiation. In general, however, radiation treatments are very well tolerated, the expected side-effects are confined to the treatment area, and abate after completion of therapy. Of more concern are possible "late" effects, which tend to be long lasting or permanent if they occur. Specifically, impotence develops in about 50% of irradiated patients, chronic diarrhea in 5%, and bowel or urethral obstruction requiring eventual surgery in 5%. Incontinence is rare (1%) as are second cancers caused by radiation (<1%). Giving the treatment as many fractions, instead of in one large dose, helps reduce the incidence of late reactions. The patient returns for follow-up after completion of treatments, eventually being seen once or twice per year for their routine check. Overall, radiation treatments are safer than surgery.

Another method of giving high-dose radiation to the immediate prostate area is by using an"Interstitial Implant" also known as "Brachytherapy" (for "slow therapy"). It may be used alone for early stage prostate cancer, or as the "boost" after External Beam Therapy described above. Typically, "implantation" uses Iodine-125 as it's radiation source, permanent seeds are placed into the prostate which have an average life of 84 days. A template is placed over the perineal area and a "gun" shoots in the seeds along a pre-arranged plan. General or local anesthesia may be used, with a hospital stay of 2 days or less. The dose to the prostate is about 150 Gray with implant, that is about twice as much as with External Beam treatment. However, implant is a very LOCAL treatment; it doesn't do anything to treat lymph nodes in the pelvis, and certainly nothing for more distant disease. With an "implant" the patient is actually radioactive, except the dose falls off so quickly with increasing distance from the radiation sources that it is insignificant at one foot away. The typical side effects of implant alone are one-half those of conventional External Beam Therapy, so impotence is reduced to about 25% or less. Obviously, this advantage disappears if the treatment is combined with External Beam treatment, whole pelvis.

Free-hand use of Iodine-125 or Gold-198 seeds was common for 15 years in the 1970's and 80's until it was reported that these implants failed to achieve cancer control more often than External Beam therapy or Radical Prostatectomy. However, the seeds were not being placed to gain an optimal radiation distribution by free-hand techniques, so it was not surprising that cancer was being missed. Significant improvements in technology have re-awakened interest in implants. Using Trans-Rectal Ultrasound Guidance with "fixed templates" may improve dose distribution, and this is available at University Academic Centers Today-- results are now pending.

Radiation Therapy After Surgery is often necessary since, on average, 50% of patients are "upstaged" at surgery from"B" to"C" and are thus at high risk for local recurrence without further therapy. The urologist often does know this during the operation; it is when the prostate specimens to to the pathologist that a report of "positive margins", "extracapsular extension", "seminal vesicle invasion" and/or "positive lymph nodes" is made. The truth is, then, that the patient was CLINICALLY stage "B" but PATHOLOGICALLY (microscopically) stage"C" and will need more treatment, if cure remains the goal. Another common scenario is that the PSA, which normally falls very low after surgery, starts rising again over the ensuing 18 months. It is then clear that surgery failed to remove all the disease, which is now growing back. However it is diagnosed, the usual treatment for residual prostate cancer, confined to the pelvis after surgery, is "Post-Prostatectomy Radiation Therapy" and means the patient will now have the potential side effects of both modalities.

Studies have shown a striking advantage to adding Radiation Therapy if all of the cancer was not removed at surgery. Specifically, if surgery only is done,"actuarial survival" (that is corrected for normal life expectancy) was only 25% at 15 years if cancer remained, versus 90% at 15 years if radiation therapy was used afterwards . The "local control" of the cancer in the pelvis is only 32% AT 15 years if surgery alone was used, compared to 96% if radiation therapy was added afterwards . Thus there is a clear advantage to adding radiation in the face of incomplete cancer removal at surgery. However, there is a price to be paid (besides financial) in getting post-operative radiation therapy. Leg swelling ("edema") occurs in 9% of patients irradiated after surgery, compared to just 2% in those getting surgery only. The chance of retaining potency after "nerve-sparing" prostatectomy will be reduced (although still possible) after radiation. Moreover, the other side effects mentioned about radiation therapy (rectal irritation, urinary frequency, incontinence) will be somewhat more likely to occur after surgery to the area. The overall conclusion is that while post-operative radiation upstaged to stage C during surgery may not cure the disease, it helps control local disease and may reduce early cancer deaths in these patients-- and so is typically recommended by both urologists and radiation oncologists.

Hormonal Therapy:

Recall that both surgery and radiation therapy are local treatments -- they cannot be used to cure disease that has migrated outside the pelvis to other body areas (although they may afford symptom relief in other locations). To have a chance to kill escaped cancer cells that have spread to distant body areas requires treating the whole body ("systemic treatment"), usually via the bloodstream. While conventional chemotherapy (as is used for breast cancer or leukemia) has been very disappointing for prostate cancer, it has been found that prostate cancer is often impacted by hormone treatments . This may be owing to prostate cancer starting more often in men with high testosterone,and the cancer needing this male hormone to flourish.

The surest way to lower a man's testosterone level is surgical CASTRATION -- that
is cutting out both testicles (recall that eunuchs don't get prostate cancer). Admittedly,
this sounds drastic, obviously any remaining potency and fertility will be lost. Note that the operation leaves the scrotal sac, so it's not quite as drastic as complete gelding. Castration is relatively inexpensive (compared to years of the other medicines to be discussed) but has the drawbacks of being psychologically unappealing, and of failing to completely wipe-out the man's male hormones! This is because the adrenal glands, which lie on top each kidney, make about 5% of a man's male hormones-- enough to continue to stimulate prostate cancer growth! Today, fewer men than in the past opt for castration to treat prostate cancer.

There are several widely available medicines to impact on blood hormone levels, and which are commonly used for prostate cancer patients. Initially, patients were given high doses of the female hormone "Diethyl Stilbesterol" (DES) . In a large Veteran's Hospital Study, this treatment caused an increase in heart attack deaths, while not improving prostate cancer survival. Using DES in lower doses (1 mg./day) or other female hormones called "progestins" (e.g. megace) does suppress the "instruction for the production" of testosterone. Female hormones do this by telling the body's "master gland", the pituitary in the brain, not to release substances that will tell the testicles and adrenal glands to produce testosterone. This is a complicated (although effective) way to reduce testosterone, but still does not block it's production altogether Also, female hormones can cause breast swelling ("gynecomastia"), hot flashes, impotency, and perhaps a higher risk for heart problems. It was obvious that some better treatment was needed to reduce male hormones in prostate cancer.

Some older drugs prevent the adrenal gland from making testosterone, such as "aminoglutethamide" (which destroys adrenal tissue) and "ketoconazole" (an antifungal drug). While these drugs are inexpensive, doctors are reluctant to use them since the testicles still make testosterone, they have side effects, and better drugs are now available (as below).

Leuprolide is a drug which inhibits the pituitary's signal for the body to produce testosterone, like female hormones do, but without the side-effects of female hormones. Specifically, it does this by blocking the signal, carried by a hormone called "Gonadotropin Releasing Hormone" (GRH) between the hypothalamus, which instructs the pituitary, and the pituitary gland itself. The net result is that the testicles and adrenal glands still produce some testosterone, but much less. Interestingly, when first starting leuprolide one can have a temporary worsening of bone pain ("flare") from prostate cancer spread, as the body adjusts to hormonal alterations.

Flutamide prevents the production of testosterone in the testicles and adrenal glands by blocking a necessary enzyme for testosterone production. This enzyme, called "5-Alpha Reductase", is the main pathway for male hormone synthesis.

combining leuprolide and flutamide is called "total androgen blockade", and is the most effective method to reduce the body's testosterone level. This, then, is the method of choice to absolutely prevent prostate cancer from being stimulated by testosterone, with a minimum of side effects. It is also the most expensive way! However, this treatment actually improves survival in advanced prostate cancer. In the past, doctors were taught that while hormones helped symptoms, they did not prolong life for prostate cancer patients. This is no longer true with Total Androgen Blockade, which has been shown to extend survival over just partial blockade (i.e. flutamide or leuprolide) alone.

Latest Effective Treatment

The latest effective treatments have come from refinements of the above conventional treatments. New therapies are tested in Clinical Trials, by such organizations as the Radiation Oncology Therapy Group (RTOG) or Southwest Oncology Group (SWOG). For surgery, using "cryosurgery" (available at Cleveland Clinic) freezes prostate cancer cells locally, and helps preserve potency by sparing nerves to the prostate. This and Nerve-Sparing prostatectomy(discussed previously) are only helpful if disease is localized, at most stage "B". If disease has spread into the seminal vesicles or beyond the prostate capsule (stage "C" ) or to local lymph nodes (stage"D" ) then some regional therapy besides surgery will be necessary for cure.

Radiation Therapy advancements have been considerable. Several decades ago, before high-energy LINACs were available, the skin and muscle got much more dose, and the patient often had to be treated from 6 directions to even out dose to the prostate. The most advanced departments now use "Conformal Three-Dimensional Treatment Planning" for External Beam therapy, to maximize the dose to the prostate but minimize the dose to surrounding normal tissues. The least side-effects for localized prostate cancer is gotten by"Stereotactic Interstitial Implant" whereby the iodine seeds used and precisely placed under radiologic guidance, the risk of impotence is as low as 10% (lower than any accepted surgery). This is available at University Academic Radiation Oncology Departments, but used by itself is only proper for stage "A" or"B" disease.

For stage "C" or greater disease (and remember that on average 50% of "A" and "B" are actually stage"C" when examined surgically), giving wider External Beam radiation fields to the whole pelvis and/or abdomen has NOT increased survival. Nonetheless, most Radiation Oncologists do wish to treat the pelvis, believing it lowers the risk for failure there. We know radiation seems to work, since by comparing life-expectancy rates of treated patients (stage "B" and less) to people without disease, treated patients appear to live, on average, just as long. This is in spite of the fact that recent reports show PSA tends to increase in over 70% of patients watched over 5 years who had radiation only as their treatment. An increase in PSA does NOT necessarily mean return of clinically significant (symptom causing) disease. Recall only 5% of men actually die of (as opposed to with) this disease. Overall, 40 years of experience show radiation to be safe and effective treatment.

An exciting advance in those with probable stage"C" or early "D" disease is giving Neoadjuvant Hormones before Radiation Therapy. "Neoadjuvant" means that the hormones (leuprolide/flutamide) are given for 2 or so months prior to the definitive therapy (radiation or surgery) to "hormonally cytoreduce" (shrink) the cancer. This treatment has been shown to result in better local control of cancer in the pelvis, and a better "disease-free-survival" (apparent cure) at 5 years. There are several current studies to see whether hormones plus radiation therapy, versus radiation alone, is superior (i.e. RTOG 92-02, RTOG 94-08, RTOG 94-13). Early results show combination therapy with hormones and radiation is better than radiation alone-- after all, we are treating the whole body with hormones ("systemic treatment"), while surgery or radiation are by definition only local therapies. Recall that Total Androgen Blockade has now been shown to improve survival in advanced prostate cancer!

Palliation (Symptom Relief)

When prostate cancer is stage IV, or "D2", the most advanced type with distant disease spread through the body, the objective is no longer cure but palliation (meaning relief of pain and other symptoms). The patient would be made as comfortable as possible, and narcotic medicines like morphine (which Osler called "G-d's own medicine) should never be withheld for fear of causing "addiction". Using "Fentanyl Patches" applied to the skin helps give a continuous amount of narcotic, eliminating the problems of forgotten doses, "loss" of narcotics, and smoothing out the dosing for less disturbing "highs and lows". Importantly, Radiation Treatment can help pelvic pain, urinary obstruction, bleeding and bone pain in 80% of patients. It is also useful for reducing the symptoms, and even extending survival, in patients with spread to the brain. Sometimes radiation therapy is used as an emergency measure when the cancer spreads to the spinal column and threatens to cause paralysis by pressing upon the spinal cord. Any patient with prostate cancer who experiences new weakness of the extremities, numbness, or loss of bowel or bladder function must be brought into the Emergency Room immediately to see whether the tumor is compressing the spinal cord causing these symptoms. Up to 60% of new back pain in a cancer patient is caused by spread of cancer there. The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for "epidural spinal cord compression". If this is caught early, and treatment is given, permanent paralysis may be prevented. It is unfortunately uncommon to reverse symptoms of paralysis once they have set it, however, so quick recognition is essential.

As mentioned, radiation treatment can be very helpful for metastatic prostate cancer. A relatively new method of radiation for spread to the brain (one of the most common areas of spread) is "Stereotactic Radiosurgery", where multiple beams of convergent radiation are aimed onto the area(s) of spread in brain, in a single painless session of one afternoon. This is usually followed by conventional External Beam Radiation. The advantage of Stereotactic Radiosurgery is that it can give a very high dose of radiation to areas of brain metastasis, and possibly enhance survival for these patients, without the risk of an open brain surgery from a neurosurgeon.

Other options for patients in severe pain for multiple areas of spread to bone include "hemi-body" radiation, and "strontium-89". Hemi-Body radiation uses a low dose (6 to 8 Gray) in a single treatment to the upper or lower body to treat multiple areas of bony involvement; some anti-nauseants are usually necessary and it lowers blood counts. It is over 90% effective for pain relief lasting an average of 6 months. Strontium-89 is an injected radioisotope that goes through the bloodstream to all bony areas, and is especially attracted to cancerous areas. It also lowers blood counts but is very effective at palliating pain. It can only be done once. If no relief is gotten from medications or radiation, neurosurgical techniques to cut sensory nerves can usually afford relief, to this small population of patients. Committing suicide because of unrelieved pain should NEVER be necessary with pain science today. The patient with newly diagnosed prostate cancer should not rely on any one therapy, but instead should use a combination approach to maximize the chance for success Specifically, besides the conventional medical therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative therapy that you believe in, a program of spiritual renewal, "mind over cancer', nutritional therapy and exercise. Keep the most positive attitude possible-- research has shown this to be an important factor in survival. CancerAnswers has a transcript available on reasonable alternative treatments which you can order through our web-site . Using a true "multi-modality" approach will give the confidence that you have done everything possible for a happy outcome, and certainly improve the current quality of life.

In conclusion, new techniques utilizing surgery, radiation therapy and hormonal therapy are showing better survival rates than ever before for prostate cancer. If cure is the objective, consider getting treatments at a University Academic Center and joining ongoing research trials which offer the latest therapies. The future has never looked brighter for prostate cancer patients!

The most difficult part about prostate cancer is that it can be challenging to diagnose. Unlike the symptoms of AIDS or even the more prevalent signs or pregnancy, signs of cancer aren't always clear and can be misdiagnosed as other illnesses.

This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Prostate Cancer. Much more, including latest additional treatments for Prostate Cancer can be found on our order page. Thank you for using CancerAnswers as your information resource.