The treatment of prostate cancer continues to remain controversial. This is because there are no well-controlled clinical studies regarding any specific form of therapy. There is, however, a significant amount of clinical experience, which has been gathered over many years of treating patients with prostate cancer and some truths have emerged that appear to be generally agreed upon.

In discussing the appropriateness of treatments for patients with prostate cancer, it is very important to develop an understanding of the probable stage and grade of the cancer. This implies that tests will be required, including the PSA blood test, and in some cases, an acid phosphatase, bone scan, chest x-ray, CT scan of the abdomen and pelvis, cystoscopic exam, kidney x-rays and/or lymph node sampling. There is a wide variety of tests, all of which are not necessary in every patient. The sequencing of these tests is being modified by research currently underway. These tests will help your physician and you understand (to the best of our ability at this date) the possibility that in your case the disease is organ-confined and, therefore, amenable to therapies directed specifically at the prostate gland.

In general, options for treatment of prostate cancer range from conservative to aggressive. As mentioned previously, the discussions regarding your particular case will be made on an individual basis depending on several factors, including the apparent aggressiveness of the tumor, your age, your associated medical problems, and the probability that the tumor is confined to the prostatic area.

It is true that many men who have prostate cancer do not need to have any therapy. This is particularly true in men who are greater than 75 years of age, are in poor health with associated medical problems, and who have well differentiated prostatic cancers (meaning that their cancer under the microscope looks to be non-aggressive). No exact age limit can be set specifically because these various factors have to be individualized for each patient.

Watchful Waiting (Observation)

Recent studies have suggested that men who are older (72 years of age or greater) and who develop a well-differentiated (non-aggressive) cancer may do quite well with observation only. Observation implies serial physical examinations and PSA blood tests to determine the potential growth of the tumor locally or at distant sites. Research to date suggests that approximately 10% of men fitting those criteria (72 years old, well-differentiated cancers, early stage) who are not treated will die of their prostate cancer within the next ten years. Given the patient's age group, the patient can expect (during the same time) approximately 40-50% mortality from other non-prostate related causes. It is important, however, to remember that although only 10% of these selected patients may die during this interval, 50-65% of them may, in fact, show progression of the disease locally, which can cause symptoms of prostatic outlet obstruction or other local symptoms and that as many as one-third of these patients will develop metastasis of the disease to their bone (or elsewhere) producing pain and requiring hormonal therapy. Nonetheless, in this select group of patients, observation is a viable alternative to the other more aggressive management techniques.

Aggressive therapies are aimed at the potential of curing the prostate cancer by removing all of the cancer cells from the patient's body. These aggressive therapies include radical prostatectomy, radiation therapy (including external beam and brachytherapy techniques), and cryosurgery. Each of these therapies have some specific areas of potential benefit and also some specific associated risks. It is important to understand these potential risks and benefits in order to make an adequate conclusion about your treatment plan.

Radical Prostatectomy

Radical prostatectomy is a surgical procedure which can be performed in two ways:

1. through a lower abdominal incision which allows for the simultaneous removal of the lymph nodes which drain from the prostate gland.
2. through the tissue called the perineum which lies between the scrotum and the rectum.

The perineal approach does not, by itself, allow for removal of the lymph nodes, which drain from the prostate and would require a second procedure to sample these lymph nodes. This second procedure can be done laparoscopically, i.e., through a series of scopes being inserted into the abdominal cavity in order to visualize and remove the lymph nodes.

Radical prostatectomy is a surgical procedure, which has been performed for many years. It involves complete removal of the prostate, the attached seminal vesicles (which are storage organs for the sperm) and the distal vas (which are conduits for the seminal fluid). If the prostatic cancer is completely contained within the prostate gland, radical prostatectomy should offer an extremely high efficiency in eliminating (and potentially curing) the prostate cancer. On the other hand, even with the current practice of PSA blood testing and improved efficiency of earlier diagnosis of prostate cancer, as many as 20-30% of patients who are presumed to have prostate cancer localized to the prostate gland will have signs of pathologic evaluation of microscopic spread beyond the prostate. Thus, the potential cure from radical prostatectomy alone probably, today in the PSA era, ranges from 70-80%.

Technically, this surgery typically requires 2-3 hours to complete. The patient is in the hospital for 2-3 days with the abdominal procedure versus 1-2 days with the perineal procedure. The complications of radical prostatectomy are impotence, which occurs in 30-50% of men with good preoperative erections if a nerve-sparing approach to the prostatectomy is undertaken (it is important to remember that postoperative potency can be achieved by various different modalities even if it is lost due to surgery or other aggressive treatments of the prostate cancer). The other primary complication associated with surgery is difficulty in controlling urine. Approximately 1-2% of men will have extreme difficulty controlling urine which requires them to wear pads throughout the day, and which usually is severe enough that they consider some alternative way of managing their urinary leakage, including placement of artificial sphincter or injection of periurethral collagen.

Additionally, approximately 20-25% of men will complain of mild stress urinary incontinence. This stress urinary incontinence, commonly occurring in women, is an inadvertent loss of drops of urine with coughing, sneezing, lifting, etc. This mild incontinence may require the patient to wear a liner inside of their underclothes to control this problem. Additional complications which may occur include bleeding at the time of surgery and urethral stricture formation, which occurs in approximately 2-3% of patients. By donating one's own blood (autologous donation) and due to refinements in surgical technique, the risk of needing to receive blood from an unknown person is less than 1%.

The advantage of surgery is that the cancer is eliminated from the body if the patient's cancer cells are completely contained within the prostate gland. Such patients should have nearly the same life expectancy as men of the same age and health who never had prostate cancer. On the other hand, as mentioned previously, undiagnosable microscopic extension of the cancer beyond the prostate gland may be found in 20-30% of cases. In these cases, the addition of radiation therapy (in smaller doses) may help eliminate any residual cancer cells. In general, radical prostatectomy is indicated for healthy patients with a cancer that is limited to the prostate in which the patient has at least an 8-10 year life expectancy.

Radiation Therapy

Radiation therapy uses high-energy rays to damage and destroy cancer cells. Radiation therapy can be delivered in different ways, including an external beam source or interstitial radiation therapy (where needles are passed into the prostate directly and radioactive seeds are placed into the prostate through these needles). External beam radiation therapy generally requires approximately 35 visits to the radiation therapist, typically each day during the work week of Monday-Friday for seven weeks. Most studies have suggested that interstitial radiation therapy (seeds) provide similar results in terms of control of cancer, as there seem to be with external beam radiation. If patients with presumably localized prostate cancer are treated with external beam radiation therapy and rebiopsy is performed at approximately 2 years, approximately 20-30% of patients will still be found to have microscopic cancer within the prostate.

Prostatic brachytherapy (or interstitial implantation of radioactive seeds) is another way of achieving high doses of radiation in the prostate. In this procedure, needles are passed through the perineum (the tissue between the scrotum and rectum) into the prostate under ultrasound guidance. Tiny seeds or pellets are then deposited in the prostate through needles. The seeds stay in permanently and slowly produce radiation to the prostate over several months.

The best results reported with radiation therapy seem to suggest relatively equal cure rates with surgery to approximately 6 to 7 years after treatment with most evidence suggesting that for periods of 10, 12, or 15 years after therapy the chance of being free of prostate cancer is less with radiation therapy than it is with radical prostatectomy. Therefore, for the first 6-8 years after treatment there is probably little difference in the chance of being alive in patients who are treated with radical prostatectomy as compared with radiation therapy. However, as the length of time increases 10 or 15 years, there is a probable advantage to radical prostatectomy in terms of prostate cancer control.

Complications seen with radiation therapy are similar to those with surgery including impotence in 40-60% of patients, incontinence in 5% of patients (this typically is an urgency-type incontinence) and stricture disease occurring in 2% of patients. A main complication, which occurs only with radiation therapy, is related to injury and irritation of the bladder or rectum, which occurs in approximately 5-10% of patients, some of whom have these symptoms of diarrhea or marked irritation of their bladder causing frequent urination through the remainder of their lifetime. The advantage of radiation therapy is that it is generally easier for patients to tolerate than is an operative procedure.

Radiation therapy may also be required in those patients (previously mentioned) who are found to have microscopic extension of disease at the time of radical surgery. In those treated with radiation, a reduced dosage may be given which is, therefore, better tolerated but may serve to sterilize any additional smaller number of cancer cells which are found to be beyond the scope of the prostate at the time of the initial surgery.

Cryoablation

Cryoablation of the prostate, or cryotherapy, is the destruction of the prostate by the application of freezing cold temperatures. Essentially the prostate dies of "frostbite". Metal probes (usually 5) are positioned under ultrasound guidance through the perineum into the area of the prostate. These probes are then cooled by a special machine, which uses liquid nitrogen to freeze of the prostate. Tissue temperatures within the ice ball range from -15 to -190°C. Although the mechanisms of cellular death are very complex, simply stated, chemical reactions occur within the cell which cause it to fail to be able to operate at such low temperatures, and, therefore cause the cell to eventually rupture (much like liquid in a glass bottle will rupture when exposed to an extremely cold environment). In addition, the cells are exposed to a lack of oxygen and also die when blood flowing to the cell freezes.

One of the unknown factors regarding cryosurgery is the long-term effectiveness. The question of whether long-term (10-15 year cure rates) will be equivalent to those with open surgery or radiation therapy will not be answered for many years, given the recent nature of the development of this technology. However, initial results seem promising. Complications using cryosurgery include urethral damage and tissue sloughing (dead tissue coming out of the urethra), urinary retention (inability to urinate), irritative voiding symptoms (feeling of discomfort or urinary infection), pelvic infection or abscess, and rectal fistula (an abnormal connection from the prostate to the rectum). Impotence has developed in approximately 50-70% of patients, depending on age, but with improved experience cases of incontinence, stricture, and rectal fistula have become rare, occurring in approximately 1-2% of patients. Some patients require tissue to be removed from their prostate to resume voiding.

Emotional Toll of Prostate Cancer

When a patient becomes aware that he or she has a cancer, the reaction patients typically have is similar to that of the loss of a loved one. The person has to come to understand the nature of the cancer and go through various phases of adjustment, including guilt, blame, denial and finally acceptance. Prostate cancer is generally a slower growing tumor than many human cancers and, therefore, there is a great deal of hope for most patients with this disease. It is important for the patient to have a positive mental attitude toward his cancer and to be prepared to do everything humanly possible to improve his general state of well being and to attack the cancer with the appropriate therapy when necessary. We hope this brief monograph on the current approaches to the treatment of prostate cancer is informative for you and for your family members. Please know that our urologic oncology team is always available to discuss any problems with you, and to answer any questions that you have regarding your disease.

• Robert C. Flanigan, MD
• Steven C. Campbell, MD, PhD
• Mila Yap, RN
• Kathy Marchese, RN