HisandHerHealth: Information About Sexuality, Prostate, Incontinence

Prostate cancer has always been a poorly researched field of medicine. In fact, less than 10% of the money spent on breast cancer research for women is spent on prostate cancer research. In 2007, the diagnosis and treatment of prostate cancer continues to be controversial but better defined.

Most men see their physician for an annual prostate exam and PSA blood test; at what age they begin these examinations is debatable. American Urologic Association states that men 45 and older should have annual examinations unless they have a family history (father or brother) of prostate cancer or, if they are African-American, they should consider annual evaluations at 40 years of age. But all agree that men 50 years or older definitely should have an annual digital rectal exam and probably a PSA.

You wonder why I use the word �probably.�

Believe it or not, there are many physicians, particularly non-urologists, who feel that early diagnosis of prostate cancer and earlier treatment does not improve survival figures. They feel there are many false positives, and the biopsy rate resulting from these �false elevations� in PSA are costly, nonessential, and do not improve the treatment and/or life expectancy of patients with this disease.

Fortunately, most men are not listening to the nay-sayers, and most men are learning to go to their physician and get their annual exam. The end result has been that the survival figures for prostate cancer have dramatically improved in the last decade. Interesting enough, the numbers of cases of prostate cancer have decreased as well. Probably because over the last 20 years, patient education, annual male visits to their doctor, and the use of PSA has picked up what at one time would have been undiagnosable prostate cancer, made it diagnosable, biopsy-proven and a treatable disease. When a biopsy is suggested by a physician, usually a urologist, the indications are abnormalities on digital rectal exam, or elevations or significant changes in the PSA values. The rate of positive biopsies overall are greater than 40% when compared to about 15% for biopsies of the breast in women with suspected breast cancer. We do not hear physicians saying, �you should not be doing biopsies in women who may have a breast mass.�

What�s New

Newer diagnostic tests are on the horizon. A urine test called PCA3 may help many physicians in diagnosing cancer that cannot be proven by biopsy even though the suspicion of index is quite high. The test involves massaging the prostate, collecting urine, and then analyzing the urine for an enzyme that is produced by prostate cancer cells that are excreted in the urine after prostate massage. Newer markers, possibly more sensitive markers, recently found at Johns Hopkins may also have some value in the future. Overall, the use of PSA, free PSA and PSA percentage along with PCA3, and newer serum markers will increase the diagnosis of prostate cancer at an earlier stage in time with less false positives and higher biopsy rates, and possibly higher positive biopsy percentages.

At this time, in 2007, the treatment of the disease appears to be fairly established. Assuming the disease is localized to the prostate and relatively low-grade (85%), local therapy to the prostate itself is well established. The use of radical surgery, radiation therapy, cryotherapy or (in older men with minimal disease) watchful waiting, appears to be the standard. Surgery includes the gold standard, i.e. open radical prostatectomy or the newer robotic techniques, which have a lower morbidity, lower blood loss, and possibly a higher continence rate and potency rate.

Both robotic radical prostatectomy and the standard techniques can preserve sexual function, and with either procedure the erectile function rate is greater than 70%, particularly in males less than 60 years of age and/or potent prior to the procedure. The addition of drugs like Viagra, Levitra and Cialis can increase and/or improve male potency and erectile function.

Radiation therapy has dramatically improved with Intensity-Modulated Radiation Therapy (IMRT) and better computerization of the distribution of the radiation. The radioactive seed technique continues to improve with the net results that patients have survival rates and PSA progression rates for low-grade, low-stage disease up to about 15 years similar to surgery. The complications of radiation appear to be diminished with less radiation cystitis and proctitis. Proctitis is inflammation of the lining of the rectum.

On the other hand, erectile dysfunction in 2 to 5 years is as high as 70%, the opposite of surgery. Although, this too can be helped with the use of the oral ED drugs. Permanent, severe incontinence from surgery and radiation is less than 5%. However, when it occurs in radiation it is very difficult to treat, and when it occurs with surgery there are many new surgical techniques to regain urinary control.

Cryotherapy is definitely indicated for patients who have failed radiation therapy and have a rising PSA. Cryotherapy, for all practical purposes, causes 100% erectile dysfunction, although some have been able to salvage the neurovascular bundle by freezing only a portion of the prostate. In doing so, no one knows whether a PSA recurrence and/or life expectancy of the patient will be compromised. Both radiation and cryotherapy appear to be better if the prostate gland is relatively small.

Therefore, hormone manipulation with LHRH agonist to shrink the prostate prior to either radiation or cryotherapy is indicated and appears to give a better long-term result. LHRH agonist: A compound that is similar to LHRH (luteinizing hormone-releasing hormone) in structure and is able to act like it. Luteinizing hormone-releasing hormone is a naturally occurring hormone that controls sex hormones in both men and women. Thus, an LHRH agonist serves in a manner similar to LHRH to control the same sex hormones. An agonist achieves a normal action, often mimicking the action of a naturally occurring substance. The word "agonist" comes from the Latin agnista, contender, from the Greek agnists, contestant, from agn, contest. An agonist is a chemical contestant.

Cryotherapy is now being utilized in non-irradiated patients, particularly patients who are somewhat older and already have erectile dysfunction. The statistics are dramatically improving with cryotherapy, and we now have ten-year PSA free and survival figures that appear to match the statistics of radiation therapy by 5 to 7 years. With newer instrumentation, the complications of cryotherapy are minimal and, in fact, the techniques of cryotherapy appear to be the simplest and involving less time for therapy.

In our older population that has health problems and does not appear to have a life expectancy greater than 15 years, watchful waiting may play a role in those who have low-volume, low-grade disease. Advocating watchful waiting is not as passive as it sounds. It involves on a regular basis monitoring the patients for changes in the digital rectal exam, rises in PSA, and biopsies of the prostate on a regular basis to be sure that the volume of the disease has not increased, and that the stage and the aggressiveness of the tumor has not progressed. If there are any significant changes in the volume of disease or aggressiveness of the tumor, watchful waiting may have to be dismissed and more aggressive therapy may need to be instituted. Some people are advocating, in fact there are clinical trials going on at this time, that drugs that block the metabolism of testosterone known as 5-alpha reductase inhibitors should be used in patients who have watchful waiting and that the statistical outcomes are better if the patients are using watchful waiting along with a 5-alpha reductase inhibitor.

Other treatments or options

So now, we have summarized the controversial aspects of prostate cancer, meaningful diagnosis, need for biopsy, and treatment of localized disease. What about those cases that begin to fail, where the PSA rises after definitive therapy, the patient begins to develop extra prostatic disease with local recurrence, nodal metastases, bone metastases and, even worse, soft tissue disease such as spread to the lungs, brain and liver?

The simplest form of progression is really biochemical failure where the PSA rises and the physician is unable to demonstrate either local recurrence or metastatic disease. Most physicians advocate, and the standard of care has been, no treatment at all until the patient becomes symptomatic, and then treatment with hormonal manipulation with an LHRH agonist is indicated. Others feel earlier, more aggressive therapy should be instituted.

In the case of patients where the prostate gland has been removed, a rise in the PSA will frequently indicate local recurrence in the prostate fossa. Most of the time, digital rectal exam does not reveal these cancer cells. Metastatic workup with an MRI of the pelvis and prostate as well as a bone scan show no evidence of metastases. Local radiation to the prostate bed is the indication of choice, usually when the PSA rises above 1.0 or higher. Many, however, feel that chemotherapy and/or chemotherapy plus hormonal manipulation should be instituted in these situations. Possibly a combination of chemotherapy followed by hormone manipulation followed by irradiation plus intermittent hormonal manipulation may be the ideal situation.

There are several studies going on now in which biochemical failures with no evidence of prostate cancer spread is being treated with earlier-than-normal hormonal manipulation and being compared to earlier-than-normal chemotherapy with Taxotere and hormonal manipulation. There are also studies being planned in which immunotherapy is to be instituted during biochemical failure, and immunotherapy alone, as compared to Taxotere plus immunotherapy, is a potential way of handling this problem. Many cases, however, are not just biochemical failures.

The bone scans are positive indicating bone spread where the MRI shows no disease, and in some cases, you can actually find prostate cancer in the lung, brain or liver. Historically, this advanced form of prostate cancer has been treated with hormonal manipulation using an LHRH agonist. Chemotherapy with Taxotere and other drugs, as well as immunotherapy with drugs such as Provenge, are now in clinical trial. Overall, one must remember that chemotherapy and immunotherapy will not work as well with larger volumes and bulkier disease. It may only control the disease for a finite period of time. That is why immunotherapy and chemotherapy are being considered at an earlier stage when the disease is not higher in volume or bulkiness and is mostly biochemical failure with PSA elevation.

Advanced Prostate Cancer Treatment

The three modalities that are being used for advanced prostate cancer outside of the prostate gland include hormonal manipulation, chemotherapy and immunotherapy. Let us look at some of the logic that may help patients decide which of these therapies may be better in the future.

Hormonal manipulation is based on the theory that prostate cancer cells grow with testosterone, and when testosterone is removed the cells basically self-destruct and explode. Unfortunately, 100% of the prostate cancer cells do not respond since, if that were the case, hormonal manipulation would cure prostate cancer rather than control prostate cancer. There appears always to be a cluster or clone of cells that are resistant to hormonal manipulation, and when hormonal manipulation is instituted the only cells left after the massive destruction caused by this testosterone deficiency are the cells that are resistant to this form of therapy. They continue to progress, disease recurs, and the patient develops further advancing disease. The urologist who discovered this principle received the Nobel prize in 1928. His concepts have been the basis for the treatment of advanced prostate cancer.

Many feel that the non-continuous use of hormonal manipulation with LHRH inhibitors slows the growth of the hormonal and resistant cells for a longer time to PSA progression and a longer life. Maybe, instead of giving continuous LHRH drugs with the long-term complications of osteoporosis, muscle weakness, chronic fatigue, cognitive disabilities and central obesity with associated dyslipidemia of an abnormal fat quality and quantity in the serum, intermittent hormonal manipulation may decrease the incidence of the above problems and, in some cases, may also improve sexual function during the non-hormone-treatment periods.

Chemotherapy is beginning to be used in a more aggressive manner and at an earlier stage. Taxotere is the first chemotherapeutic drug to be FDA approved for advanced prostate cancer and appears to improve life expectancy in this group by approximately 3 to 4 months. On the other hand, earlier use of this drug may be more beneficial and, as we stated earlier, is being tested in earlier disease, particularly biochemical failure. Other drugs and combinations are also being tested. In general, however, chemotherapeutic agents work during the rapid growth phase of the cancer so that slowing of the prostate cancer by first treating with hormonal therapy may not be the best way to deal with the problem.

Chemotherapy should probably be given first before hormonal manipulation to maximize the effects of the chemotherapy on the growth phase of the disease. Hormonal manipulation may be considered after the chemotherapy rather than before, as is the standard now. Intermittent hormonal manipulation along with intermittent chemotherapy may be a more ideal way of treating advanced prostate cancer.

The newest form of therapy for advanced disease is immunotherapy. Several companies have developed �vaccines� to treat prostate cancer. Dendreon, with its product Provenge, was recently fast-tracked by the Food and Drug Administration, and even though 13 of 17 consultants advised the FDA to approve Provenge, the head of the FDA declined and asked for more sufficient data on efficacy. Overall, everybody would say that Provenge is an extremely safe drug and probably has efficacy, and many are pushing for the FDA to approve this drug at this particular time.

Provenge is a infusion of specialized white cells that have been stimulated to the PAP surface antigen of prostate cancer cells. Blood is removed from prostate cancer patient. The specialized white cells known as dendritic cells are removed from the blood and incubated with broken cancer cells whose surface PAP antigens are present. After a three-day incubation, the dendritic cells are infused back into the patient, usually cycled every week for three weeks. The 39-month survival figures for the Provenge-treated group in the initial two studies was significantly superior to the placebo group, particularly in the patients who had low-grade disease.

Immunotherapy may be playing a bigger and bigger role in prostate cancer treatment as the years go on. Obviously, immunotherapy will work better when the immune mechanism is functioning best. Therefore, chemotherapeutic agents should probably not be instituted until immunotherapy has been allowed to maximize its effect on the immune responses.

Early prostate cancer appears to have clearly defined treatment modalities even though continuing to improve or have been standardized. Advanced prostate cancer is in a much greater state of flux, and the modalities, although expanding, are not yet established. Hormonal manipulation will probably continue as the mainstay of advanced prostate cancer. However, chemotherapy and immunotherapy will be playing a bigger and bigger role. Combinations will also be utilized, but the order of the chemotherapy has to be seriously evaluated and tested to determine which combination will give the optimal results with the lowest side effects.

Prostate Cancer and Bone Disease

Another area of interest related to advanced prostate cancer is preventing bone spread and/or reducing or slowing the growth of bone disease. Research seems to indicate that prostate cancer cells will spread to bones when and if holes begin to form in the bone. By preventing porosity of the bones, one may be able to prevent the spread of prostate cancer to the bones. A new drug, known as a RANK Ligand inhibitor, prevents porosity of the bones and can be used for osteoporosis but, interestingly, may be an effective tool in preventing the spread of prostate cancer cells to the bone. If prostate cancer already exists it may aid in decreasing or slowing the amount of bone disease. Clinical trials are now being performed to prove the effectiveness of this kind of drug.

Bisphosphonates are already being used to slow progression of bone disease and are rapidly becoming the standard of care. There are no studies yet to prove that bisphosphonates prevent the spread of prostate cancer to the bones.

In summary, prostate cancer is an evolving diagnostic and therapeutic problem. Localized disease has evolved to the point where most physicians can agree on acceptable standard treatment modalities. Advanced disease with local failure is much more controversial. Newer techniques in surgery, hormonal manipulation, chemotherapy and immunotherapy, alone or in combination, are being used and will probably be used more in the future in patients with advanced disease. Bony metastases may be reduced or impeded with the addition of bisphosphonates and/or RANK Ligand inhibitors. The future of prostate cancer is probably here today. Continued clinical trials will give us additional answers to help all of us successfully treat localized and advanced prostate cancer. (September, 2007)

You can comment of the value of this article on our Bulletin Boards. Click here.