Prostate Cancer Treatment

  • Treatment

    Your doctor is the best source of information on the drug treatment choices available to you.

    For people who wish to avoid surgery, radiation is regarded by many doctors as a good, although not a completely equivalent alternative to treat cancer that is confined to the prostate gland. Radiation provides a cure rate comparable to that of surgery for up to 10 years for cancer that has not spread beyond the prostate gland. For longer than that, experience with radiation is still uncertain. Many experts believe that recurrence rates may eventually prove higher for radiation because of the risk that slow-growing cancer cells may remain and not become apparent for a decade. Many doctors feel comfortable recommending radiation for men over the age of 70, or for younger men in poor health, but feel that surgery is the best bet for young, healthy men.

    A modified and improved technique for radiation is called conformal, or 3-D radiation. It is based on the premise that higher doses of radiation therapy can be delivered to tumor tissue without increasing the side effects to normal structures at the tumor margins. To accomplish this, areas for radiation are carefully mapped by the computer. Reproducible ports for delivering radiation are assured by placing patients in a posterior body cast for delivery of each dose of radiation throughout therapy.

    There are two types of radiotherapy: external beam and brachytherapy. External beam radiotherapy, including conformal radiation (described above), involves a carefully targeted beam of radiation given for about six minutes. Treatments are typically given once a day, five days a week, for six to eight weeks. No hospitalization is required. Radiation is also sometimes used following surgery if there is concern that cancer cells remain after the prostate gland is removed.

    Brachytherapy is an increasingly popular treatment for early-stage prostate cancer. The procedure involves placing numerous tiny radioactive seeds into the prostate in a geometric pattern that allows radiation to reach every portion of the gland. The seeds are placed in the correct geometric pattern by ultrasonic guidance, which allows for discreet and precise placing of the radioactivity. The procedure is done as an overnight procedure at the hospital. Male patients who have brachytherapy can live as long as men who have surgery.

    Like surgery, radiation involves significant (but generally lower) risks of long-term problems such as impotence or incontinence. Approximately 50% of men in the oldest patient group (70 and older) become impotent after radiation therapy or brachytherapy. For men in their fifties or sixties, 10%-20% become impotent. The incidence of impotence is significantly higher in patients treated with radical prostatectomy. In a national report involving Medicare patients (patients over 65) treated in community hospitals, the incidence of impotence was 89% following radical prostatectomy. Major university centers report a significantly lower incidence of impotence, with patients over 70 years old having an impotence rate of 58% according to Catalona et al. at Washington University. The incidence of impotence following conformal radiation has not yet reached maturity since this technique has only been in use for approximately 5 years in terms of reported results.

    There is no risk of incontinence after brachytherapy unless the patient had a previous surgery (transurethral resection of the prostate; TURP). However, the Medicare patient group treated by surgery in community hospitals has an incidence of impotence up to 32%. Again, at medical centers such as Washington University and Johns Hopkins, where patients were treated surgically, these figures are much lower (in the range of 4%-13%).

    External beam therapy (including conformal radiotherapy) produces bladder irritation, which causes urgency and pain and frequent urination; there may also be rectal irritation with diarrhea and urgency, as well as bleeding from the rectum. These difficulties are temporary, and usually resolve spontaneously within a few months.

    Brachytherapy may cause increased urinary frequency and urgency, and diminished force of the stream due to fluid build-up, causing increasing obstruction of the prostate. However, the 1-year follow-up for brachytherapy looks encouraging in terms of both the effectiveness and duration of response as well as the side effect profile. If longer follow-up shows maintenance of these benefits, then brachytherapy will become a primary choice for treating localized prostate cancer.

    Conformal radiotherapy, for which there is only data in the literature for a 5-year follow-up, also shows promise. However, researchers need to study a longer follow-up interval before determine its ultimate usefulness for treating for localized prostate cancer.

    Neoadjuvant therapy refers to the use of hormonal therapy prior to or in conjunction with the use of other standard therapies such as radiation or surgery. There have been several reports showing that using therapy with total androgen blockade significantly increases the duration of time to progression in patients given external beam radiation. No such reports are available yet for brachytherapy.

    A “wait-and-see” approach is sometimes advised instead of active treatment. An alternative to surgery or radiation is no treatment at all, but instead keeping an eye on the progress of the cancer with regular DRE and PSA tests. Treatment options are only explored when the cancer appears to be progressing dangerously. This “watchful waiting” or “wait-and-see” approach may be indicated for men with small, low-grade, slow-growing tumors found at an early stage (Gleason score of 2 to 4). Many doctors justify this approach under these circumstances because of the likelihood that prostate cancer will grow slowly and not cause problems. Studies have shown that life expectancy is similar in men with untreated low-grade prostate cancer and in men who do not have cancer at all. Current treatments of prostate cancer also carry considerable risk of lifelong problems with impotence and urinary continence. Many doctors believe that in such cases, the risks of treatment do not justify the benefits.

    Watchful waiting may also be recommended when cancer is discovered in elderly patients or in those who have significant medical problems. People who choose watchful waiting must follow up frequently with their doctor, and must realize the risk involved: if the cancer spreads beyond the prostate gland, the chance of cure is small.

    Once prostate cancer becomes metastatic, efforts to slow its growth involve altering hormones in the body Table 03. Most prostate cancers are dependent on hormones called androgens for growth. Therefore, blocking androgens with surgical or medical castration controls tumor growth in patients with cancer that has spread to the nodes or bones, or local disease that has spread outside of the prostate into the pelvis. Since approximately 20% of the most active form of androgen (called dihydrotestosterone) in prostate cells may come from the adrenal gland, blocking the adrenal androgens is important as well, and can be accomplished by using antiandrogens such as flutamide or casodex. These antiandrogens block the androgen receptor on prostate cancer cells and prevent the entry of androgen into the cells. Although the issue of total androgen blockade (blocking adrenal and testicular androgen) versus castration is controversial, the majority of the clinical trials done throughout the world show benefits of increased time of survival in patients treated with total androgen blockade.

    One recent modification to total androgen blockade for prostate cancer that has spread is called intermittent therapy. In this mode of therapy, total androgen blockade is administered for 9 months, during which PSA levels are monitored and should be at a low point by the end of 9 months. If the PSA drops initially and then begins to rise before the end of 9 months, then intermittent androgen blockade should be stopped. However, for the patient who shows a low point at 9 months, therapy can be stopped temporarily, and the patient will be monitored until the PSA climbs back to a value of approximately 10-15 ng/mL. This time interval off therapy may be anywhere from from 9-12 months, or sometimes even longer. During the “off” period, patients enjoy a quality of life like what they had before hormonal therapy, including a sense of well-being and a return to sexual function. Intermittent therapy also dramatically lowers the cost of the expense of medications used for this purpose.

    Intermittent androgen blockade can be continued as long as the PSA continues to drop during therapy. Eventually, however, tumors will become homone-independent, at which time the only remaining option is chemotherapy. Trials are now going on to determine the best effective chemotherapy for prostate cancer.

    Surgical removal of the prostate gland is regarded by most doctors as the treatment with the highest chance of long-term cure Figure 02. A radical prostatectomy involves removing the entire prostate gland and the surrounding tissue, and is frequently recommended for patients under 70 years of age who are in good health if the tumor is localized to the prostate. This usually means that the clinical stage should be T-2b or less. The survival time after surgery is related to the extent of tumor. If the tumor is totally confined and is not extended to the capsule of the prostate, then the outlook for a long-term cure is excellent. If tumor cells are found in the prostate capsule, or extend into the margins of the surgically removed tissue, the prognosis for cure decreases. Overall, the cure rate at 15 years is 60%-70% for patients who have had their prostates removed surgically.

    In patients whose radical prostatectomy specimen shows invasion of the capsule or the margins of the tissue, radiation therapy is often given after surgery to try to destroy the microscopic tumor cells that may remain.

    Surgery carries a frequent risk of sexual problems, the degree of which is dependent upon the patient's age and sexual function before surgery. If the surgeons can spare the pudendal nerves (nerves that run close to the prostate during surgery), then the treatment of the post-operative impotence, if it occurs, can be accomplished with Viagra. Treatment with Viagra is effective in about 60% of patients who have had nerve-preserving operations. In patients for whom nerves are not preserved, impotence will be inevitable. In patients who are impotent and do not have nerve-sparing procedures, one can use vacuum constriction devices and penile implants into the corpora cavernosa of the penis. These devices may provide useful techniques to try to restore some degree of sexual function in these patients. Because the prostate gland produces semen, orgasms are dry following its removal.

    Some men also have stress incontinence after surgery, which involves urine leakage when sneezing, coughing, laughing, or during physical or sexual activity. Incontinence is defined as the need for napkins of some type to handle urine leakage, which can vary from stress incontinence to a continued and persistent incontinence, which is less common. Urinary incontinence tends to improve with time up to about a year. After a year, whatever residual incontinence that remains will usually persist.

    Medicare patients who have been operated on in university hospitals usually suffer less from impotence and incontinence than patients who undergo surgery in community hospitals.

    Because cancer cells may have spread beyond the prostate gland before removal, prostate cancer may recur after radical prostatectomy.

    Click to enlarge: Radical prostatectomy (animation and audio)

    Figure 02. Radical prostatectomy (animation and audio)

    Prostate tumors grow at different rates in different people. Prostate cancer is extremely common, but is a cause of death in only about 15% to 20% of affected men. Most patients diagnosed with localized disease live longer than 10 years after surgery or radiation, and a substantial proportion are cured. Patients with positive lymph nodes at the time of diagnosis live approximately 5 years regardless of therapy; patients whose cancer has spread to the bone at the time of diagnosis will only survive and average of 2 years using total androgen blockade. The prognosis of prostate cancer depends on how aggressive the tumor is, and, of course, on the extent of spread outside the prostate gland. Intermittent hormone therapy offers the best opportunity for providing an acceptable quality of life in those whose disease has spread outside of the prostate.

    Close follow-up with a doctor is required whether or not prostate cancer is treated. Follow-up with a doctor typically involves a PSA test and a DRE every six months. PSA levels that have risen or that are detectable at all after radical prostatectomy indicates that prostate cells are growing, and that cancer is present. Further treatment, involving surgery, radiation, or hormonal treatment, may then be indicated.

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