TREATMENT OF LOCALIZED PROSTATE CANCER -- CURRENT THOUGHTS

To make any sense of this handout, you must already understand that the diagnosis of prostate cancer has been made, and that we have no reason to suspect that the cancer has spread from the prostate. Any treatment that can control the cancer in the prostate, will therefore control all the cancer. The following are the choices that are available to us in the treatment of localized prostate cancer (stages A, B, and some  C or stages T1_{a,b, or c},  T2_{a, b, or c}, T3_{a or b} (depending on staging system used).

NO TREATMENT OR SURVEILLANCE ONLY

This option consists merely of close observation of the cancer, looking for any signs of progression with blood tests, scans and physical examinations. Specific cancer treatment will be undertaken only when problems arise from the cancer growth. While this approach may seem out of the question in most cases, withholding treatment is appropriate and justifiable in certain circumstances. The treatments might be more risky than the disease. For instance, an elderly male (in his 80's?) with localized cancer, and with no symptoms, might be better left alone. In the absence of symptoms, and in the presence of other medical situations which are more threatening, observation is correct.

In some medical environments, Sweden, for example, no treatment or observation has become a fairly standard approach to early prostate cancer. They believe that in some patients, the disease will grow so slowly that radical treatment is unneeded because patients will die of other diseases. In patients whose prostate cancers grow quickly, they feel comfortable in treating the spread with non-curative medical treatment. For the most part, this approach goes against the attitudes of most American cancer specialists. Still, observation has many supporters and must be considered in certain situations. Patients who have low stage (limited amount of cancer) in addition to low grade cancer (unaggressive cancer on microscopic examination) are the only patients in whom no treatment should be considered. Higher stage cancer or aggressive high grade cancers have a very high chance of cancer problems within a short period of time.

CHEMOTHERAPY

Chemotherapy is the use of medicines or drugs to stop the growth of cancers. Chemotherapy is used for the most part in patients whose disease has spread to other parts of the body (metastases) and is resistant to other forms of treatment.

The drugs are very powerful and work by killing cells that tend to grow quickly. Cancers tend to grow quickly, but, unfortunately, so do cells in bone marrow, gut and other areas. Anemia, weakness, nausea, vomiting, diarrhea and other side-effects can occur. Unfortunately, chemotherapy rarely cures prostate cancer, but merely palliates or temporizes the cancer growth. Because of the poor track record with prostate cancer, chemotherapy tends to be used only when all other avenues of treatment have been exhausted.

HORMONE THERAPY

The prostate gland is uniquely male. Its very existence is due to the presence of male hormones, which the prostate, and most prostate cancers, require to grow. This observation led urologists to the use of hormone reduction to treat prostate cancer in the 1940s and except for newer drugs, the principles of hormone reduction still stand today. The usual way of effecting hormone reduction are either a monthly shot (Lupron or Zolodex) or surgical removal of the testicles (orchiectomy). Pills may be added to either of these treatments to potentiate hormone reduction.

Unfortunately, hormone therapy is effective only temporarily in most patients. Seven out of ten men will have an initial reduction in the tumor, but within 2-3 years most cancers that do respond will again start to grow. Because hormone therapy is not curative, we usually do not recommend this for localized cancer with life expectancy greater than 10 years.

SURGERY or RADICAL PROSTATECTOMY

Surgical removal has one major and obvious benefit--it has the opportunity to remove all of the cancer. Removal of the entire prostate is felt to be the standard therapy for localized prostate cancer. Simply, the entire prostate is removed and the bladder is reconnected to the urethra (channel through the penis). Removal of part of the prostate or just the cancer is not recommended. Too many prostate cancers have multiple areas of involvement within the gland that are undetected, making partial removal a poor choice. Also, partial prostatectomy is not technically feasible.

Incontinence--2-5% of men will have permanent problems with urinary control-- they will require some form of protection (diapers). In those rare cases, a surgical appliance can be implanted or a sling-like device can be placed under the urethra to control incontinence if it does remain a problem.  About 20% of men will have occasional accidents which will not alter their quality of life.  A small number of men might have some incontinence with intercourse.

Impotence--The nerves that stimulate erections run adjacent to the prostate on their way to the penis. If all of these nerves are removed during total prostatectomy, impotence (inability to achieve an adequate erection) will result. In many circumstances, the nerves that create erections can be spared with a success rate between 40-70%. Not every male is a good candidate for nerve sparing because of the extent of disease. Patients who develop impotence, and even those whose erections were not adequate before the surgery can be treated with a variety of modalities. Treatment of impotence in post-prostate surgery includes vacuum pumps, self injections of medications and placement of prostheses -- all of which work, and work well in selected patients.

Blood loss--Radical prostatectomy carries with it an average blood loss of greater that one unit of blood. On occasion, but rarely, the blood loss can be more than three or even four units and require transfusion. About 1 in 10 patients require a transfusion if they have not donated blood to the blood bank. To prevent the use of bank blood many patients elect to store their own blood for subsequent use, if needed.

Surgical complications--pain, infection, anesthetic problems, pneumonia, blood clots, and heart problems can occur with any major operation. Unique to prostatectomy are injury to the rectum (adjacent to the prostate), and scarring of the new connection between the bladder and urethra, which might require a minor surgical procedure to stretch or dilate the scarred area. This can be performed in the office or in day surgery.

Recovery Time: The operation lasts two to three hours and the hospitalization usually lasts 2-3 days. All patients go home with a catheter in place, continually draining the urine into a special leg bag. You will be seen two weeks after discharge from the hospital to have the catheter removed. Most men have poor urinary control at the beginning and will require some form of protection, such as a diaper. Within three weeks, most men have achieved reasonably good control and require minimum protection and have resumed their normal activities. Sometimes the recovery is slower, but rarely more than three to six months.

External beam radiation therapy is by far the simplest of therapies. Over a six to seven week period, the patient will receive a radiation treatment lasting about 15 minutes, 5 days a week. The radiation is aimed at the prostate from many different angles in an attempt to reduce the dosage to the surrounding tissues while maximizing the dosage to the prostate and the cancer.

The major advantage of external radiation therapy is its ease of administration. Other advantages include the fact that there is no surgery, no anesthesia, and no blood loss. The biggest disadvantage is that the cancer is left in place and one must hope that the amount of radiation delivered is enough to cure the cancer. Unfortunately, with the surrounding structures being sensitive to overdoses of radiation, namely, bladder and rectum, the prostate cancer is often stunned but not cured. The chance of recurrence of prostate cancer treated with external beam radiation therapy is in the range of 6 out of 10 as measured by rising of the tumor marker PSA.

During the last two to three weeks of treatment, diarrhea and urinary urgency and frequency are quite common and on occasion so severe that the treatments need to be temporarily halted. These symptoms usually resolve two to three weeks after the radiation treatments have ceased. Permanent radiation injury to the bladder or rectum occurs in a small percent of patients creating chronic pain and/or bleeding. Difficulty with erections (impotence) occurs in 35% of patients who were having no problems prior to treatment..

Proton beams are variations of external beam radiation using a different source of radiation and always combined with standard external beam radiation. Complications with these sources of radiation seems to be higher and long term data about cure rates is not available. Very few proton centers exist in the United States.  IMRT and Ultraconformal are techniques used to reduce the amount of damage to the rectum by shooting at the prostate from various angles.

IMPLANT THERAPY OR BRACHYTHERAPY

Implants (or the technical term 'brachytherapy') are forms of radiation therapy with many of the same risks and benefits. Implants are ultrasound guided radiation treatments done under anesthesia. The operation lasts from 1 - 2 hours and hospitalization is usually not required. Some implants are permanently left in place (Iodine, Palladium, Gold (rarely)) and some are temporary (Iridium). Implants allow for higher doses to the prostate while sparing the surrounding tissues. A theoretically higher cure rate should be observed. Implants are often combined with external therapy, depending on the type of implanted radiation and the extent of the cancer.

HISTORICAL IMPLANTATION

In the early 1970s, a new approach was developed to confine radiation exposure to the prostate gland, increase radiation dosage to the tumor in order to kill the cancer, and minimize side effects. Researchers began to implant radioactive iodine (I-125 Seeds) directly into the prostate, thereby providing internal radiation therapy exactly where it was needed. The term 'brachytherapy' is the technical way of describing needle implantation. In these early attempts, surgery was performed to expose the prostate gland (which is known as open retropubic surgery) and the radioactive seeds were implanted by the surgeon, essentially freehand, without the aid of imaging techniques now available. This early method of prostate implantation began at New York City's Memorial Sloan-Kettering Cancer Center. Other radioactive agents are available, including radioactive palladium and radioactive gold. I-125 and palladium appear to be well suited for prostate implantation. They give off very low energy radiation, or X-rays, that do not travel outside the prostate gland and pose no threat to patients or those in close contact with them.

In the early 1980s the open freehand method was abandoned at Memorial Sloan-Kettering because it produced success rates inferior to prostate removal or external radiotherapy techniques. However, in 1985 reports from Denmark showed that an ultrasound directed implant allowed more precise placement of I-125 seeds without an operation or an incision. Since then this new method has used exclusively and allows very accurate placement of the I-125 and palladium seeds.

Technique for modern Brachytherapy

WHO ARE BEST CANDIDATES FOR IMPLANTATION?

Patients with small prostate tumors (early stage) are the best candidates. That means that about 50% of the patients with prostate cancer will fit this criteria. The development of more sensitive tumor detection techniques means that prostate cancer patients are being diagnosed at earlier stages, permitting more patients to become potential candidates for seed implantation.

WHO ARE POOR CANDIDATES FOR IMPLANTATION?

Patients with very large prostate tumors which have extended beyond the prostate capsule or to other organs. Patients with very large benign portions of their prostate (BPH or benign prostatic hyperplasia) or patients who have had prior prostate surgery (TURP or transurethral resection of prostate) may be poor candidates for implantation.

HOW IS IMPLANTATION DONE?

Tiny pellets or 'seeds' containing radioactive medication, such as Iodine-125 or palladium are used. Seeds are permanently implanted directly in the middle of the prostate where they give off low-level radiation continuously for up to one year. Using TRUS (transrectal ultrasound) guidance, these seeds can be positioned so that radiation is distributed throughout the entire prostate gland. Since only a small area is irradiated by each seed, relatively little radiation reaches the adjacent normal organs-the colon, which is directly under the prostate gland, or the bladder, lying on top of the gland.

The implant procedure does not require a surgical incision. Instead, the seeds-smaller than grains of rice-are contained in thin needles which are passed into the prostate gland through the skin between the scrotum and rectum. As the needles penetrate through the prostate, they are seen on the screen of the ultrasound machine and can be accurately guided to their final position. While the needles are being inserted the ultrasound probe is in the rectum. When each needle is in its correct position in the prostate, the needle is slowly withdrawn and the individual seeds are injected into the prostate gland. The ultrasound probe and the needles are removed when the procedure has been completed. The numbers of needles and seeds required varies from patient to patient depending on the size of the prostate gland.

Advantages:

* Preliminary results from centers using I-125 and palladium since 1985 with selected patients shows a very similar disease-free intervals compared to radical prostatectomy and better than external beam therapy. The first implants were done 10-12 years ago so that long term numbers are just becoming available for analysis. 10 to 15 years of follow-up would be needed to have valid results.

* Seed implantation is normally done as an outpatient procedure taking about one hour to perform. The patient usually leaves the hospital the same day as the implant procedure or stays in the hospital for one night and then resumes normal activities within several days.

* Because they are placed at the site of the cancer, the seeds can deliver two to three times more concentrated radiation to the prostate gland than external radiation therapy, which must use a lower dose because it also affects healthy tissue.

* Incontinence occurs in less than 1% of patients who have not had prior surgery.

* Impotence occurs in less than 25% of patients under the age of 70. For patients over the age of 70, impotence occurs more often.

* This procedure is well suited to older patients because it is much easier to withstand than surgery or external radiation.

Disadvantages:

* There is little information yet on the effectiveness of the implant treatment after 10 years. While the current clinical data show good results through the first five to ten years, younger men are advised more strongly to consider radical prostatectomy.

* It is very common to experience problems with urination after seed implantation. These symptoms will gradually decrease after 6 to 12 months. A small percentage of  patients will have permanent complications from the radiation to the lining of the prostate, bladder or rectum.

IMPLANTATION USING HIGH DOSE RATE AFTERLOADING WITH IRIDIUM

Another treatment variation of brachytherapy is called HDR or High Dose Rate Afterloading. In this technique, which is used in only a few centers in the USA, needles are placed into the prostate similar to seed implants. The position of the needles is then checked with ultrasound or CAT scan and a dose plan is created. With the needles in place, the patient is transferred to a special lead lined room that protects the staff from the effects of radiation. A computer driven device then places a radioactive substance, usually Iridium-192, into the needles for a measured length of time depending on the computer model. This appears to give a more exact dose of radiation to the prostate. The patient, with the needles in place, will receive one to four treatments. External beam therapy is often added to this type of radiation. HDR therapy in the USA started 4-5 years later than seed implantation programs. Therefore, data from HDR treated patients is too early to determine how effective it might be, but early information is quite favorable.

CRYOTHERAPY

Cryotherapy or 'freezing' the prostate has been around for 50 years. The original technique involved open surgery and placement of liquid nitrogen directly into the prostate cancer. The overall success rate was marginal and the technique was abandoned in the early 60's. It was reintroduced in the early 1990s with ultrasound guidance but largely abandoned because of substantial side effects. It has again been reintroduced as the cryosurgery needles have become smaller and easier to use. To date, insufficient data exists to know how effective cryotherapy might be. The frozen tissue dies and is then either urinated out or re-absorbed into the body. The major drawback of cryotherapy in the past is the fact that all of the cancer is not removed Long term recurrence rates are not known and impotence is very hard to prevent. 

DIET/HERBAL THERAPY

To date, no evidence exists to show that any dietary changes or herbal therapy will cure prostate cancer. We do know that people with high fat diets and animals fed high fat diets have a higher incidence of prostate cancer. Low fat diets may be preventative, but once a cancer is formed, changing diets will not cure the cancer. The only mineral or herb which might protect against prostate cancer is selenium according to a small number of studies. Selenium use will not cure a prostate cancer.

Follow-up to Treatment.

After your treatment is rendered, regardless of which treatment is undertaken, we will be following your progress very closely. If surgery or observation is chosen, the follow-up will be through our office. If radiation or implants are used, the follow-up will be shared by our office and the radiation therapists.

The keys to follow-up in most circumstances will be the rectal exam of the prostate, or, in the case of surgery, the area where the prostate was. We will be looking for evidence of recurrence or regrowth of the tumor. If suspicious areas occur, ultrasound and biopsies of these areas may be indicated.