Nonbacterial prostatitis (NBP) is the most common type of prostatitis, and occurs eight times more frequently than bacterial prostatitis. Nonbacterial prostatitis presents with the same signs and symptoms as bacterial prostatitis; however, prostatic fluid cultures are negative for presence of bacteria. Inflammation is evident upon prostatic fluid analysis, and can be identified by a minimum of 10 to 15 white blood cells per high power field on microscopic examination. Although controversial, implicated pathogens include Chlamydia trachomatis, Ureaplasma urealyticum, and Trichomonas vaginalis. Minocycline 100 mg twice daily, doxycycline 100 mg twice daily, or erythromycin 500 mg four times daily have been utilized in order to eradicate the suspected pathogens. Erythromycin’s antimicrobial activity is significantly enhanced in the presence of the alkaline pH in prostatic fluid, thus, it achieves high cure rates of prostatic infections. Treatment duration is approximately 2 to 4 weeks. Prolonged therapy after treatment failure is not indicated, since nonbacterial prostatitis is generally self-limiting. Adjunctive recommendations may include sitz baths, normal sexual activity, and analgesics for painful urinary symptoms.

Spicy foods, caffeine, and alcohol should be avoided; they may cause bladder irritation and spasms culminating in reflux of urine into prostatic ducts, thus exacerbating nonbacterial prostatitis symptoms. If symptomatology persists patients should be referred to a urologist for evaluation of serious conditions such as urinary bladder carcinoma and interstitial cystitis.

Conclusion

As the most accessible health care professional, the pharmacist often encounters patients with prostatitis. Treatment of prostatitis is associated with high failure rates; therefore it is paramount that pharmacists counsel patients regarding prostatitis and its treatment. Since prostatitis tends to require prolonged therapy, patients must understand the importance of compliance. Pharmacists must carefully screen for drug interactions that may decrease compliance and efficacy. Furthermore, pharmacists play a vital role in referring patients who are unresponsive to therapy for evaluation of serious underlying conditions.

Liarozole, a novel imidazole derivative, is the first retinoic acid metabolism-blocking agent (RAMBA) to be developed as differentiation therapy for human solid tumors. Most importantly, the drug has been shown to demonstrate anticarcinogenic and antitumor effects. Preclinical studies of liarozole have shown that it inhibits the growth of androgen-independent tumors, along with others, by inhibiting 4-hydroxylase, a cytochrome P450-dependent enzyme that is involved in retinoic acid catabolism. A recent study compared the ability of these two drugs to induce prostate-specific antigen (PSA) response in patients with metastatic prostate cancer that is progressing in response to first-line endocrine therapy. The multicenter, randomized trial consisted of 321 patients who had been recruited from 53 centers in 10 countries. Median age at the beginning of the trial was 72 years, with a range of 46 to 88 years. All patients except one were white. Identified as prognostic factors for survival were baseline hemoglobin, alkaline phosphatase, PSA, duration of response to first-line treatment, and performance status. Because most patients with prostate cancer do not present assessable lesions, it is difficult to evaluate objective tumor response. As a result, prostate-specific antigen (PSA) was used in this study as a marker for tumor response.

Liarozole was started at 150 mg twice daily and then increased 300 mg twice daily for the remainder of the treatment. The cyproterone acetate (CPA) dose used was 100 mg twice daily from the start of the study and remained the same unless dosage adjustments were necessary according to prescribing information. Treatment continued until clinical progression was shown or a serious adverse event occurred. Patients were followed up until death. The trial was analyzed after 232 deaths.

Prostate-specific antigen (PSA) responders were more prevalent in the liarozole group (20%) than in the cyproterone acetate group (4%), p < 0.001. PSA stabilization occurred in 64% of patients in the liarozole group. Changes indicative of continuous progression were observed in 17% of patients treated with liarozole, in contrast to 40% of patients in the cyproterone acetate group. The response was not affected by previous use of antiandrogens in either treatment group.

Prostate-specific antigen (PSA) response occurred by week 12 in 90% of responding patients. The median time to progression was 4.6 months in the liarozole group and 3.6 months in the cyproterone group. Patients who had a PSA response experienced a median survival of 25 months. Those who experienced stabilization survived for 14 months, and patients with continuous progression survived for 7 months. PSA responders had a 57% lower risk of dying as compared with nonresponders.

When comparing the two drugs, after adjustment for baseline prognostic factors, the study showed that patients treated with liarozole survived longer and had a 26% lower risk of dying than did patients on cyproterone acetate. Liarozole treatment resulted in a significantly better PSA response (20% of patients compared with 4% of the cyproterone group). Also, PSA stabilization was observed in 64% of the liarozole group. Participants in both groups of the trial reported various adverse events. In the liarozole group, the most common problems were dry skin, pruritus, rash, nail disorders, and hair loss. Patients undergoing cyproterone acetate treatment suffered from edema, nausea, vomiting, and fatigue. For the most part, these conditions were mild to moderate. Adverse events caused withdrawal from treatment for 88 patients in the liarozole group and 63 patients in the cyproterone acetate group. Most of the withdrawals occurred because of cancer-related events such as skin disorders, nausea, and vomiting.

Patients with metastatic prostate cancer usually complain of bone pain due to skeletal involvement. Advanced prostate cancer patients will also present with signs and symptoms of lymphadenopathy, lower extremity edema, renal failure, visceral metastases, anemia and cachexia. Prostate cancer and these accompanying medical conditions can lead to a lot of pain and poor performance status.

In conclusion, this trial shows that prostate-specific antigen (PSA) response is an effective way to measure the clinical benefits of prostate cancer therapies. Patients who experienced this response lived longer, had less pain, and an improvement in quality of life. Liarozole was shown to be more effective than cyproterone acetate in achieving PSA response and in treating relapsed prostate cancer.

* researchers at the University of Wisconsin-Madison treated two prostate cancer cell lines, one of which was androgen sensitive, with R1881, a synthetic male hormone, by itself and in the presence of the antioxidant vitamins C and E to collect data.

* found that androgen-sensitive cells had up to a 57% reduction in reactive oxygen species (ROS) if they were treated with both R1881 and the vitamins, compared to cells treated with R1881 alone (note: ROS are DNA-damaging particles that are thought to play a role in tumor development and aging.)

* researchers say that the findings suggest that androgens stimulate ROS production and DNA damage.

* authors conclude that antioxidants such as vitamins C and E may reduce androgen-related production of reactive oxygen species and that the findings may help to explain why previous have found that vitamin E supplements can reduce prostate cancer mortality in smokers and other antioxidants can reduced prostate cancer risk

A recent report concludes that treatment with the drug flutamide following surgical removal of the testes does not improve the chance of survival of metastatic prostate cancer patients.

* Note: the testes of male prostate cancer patients are often removed to reduce the tumor-stimulating effects of male hormones known as androgens; the anti-androgen drug flutamide has been used to block androgens produced by the adrenal glands.

* researchers at the Southwest Oncology Group, San Antonio, Texas, randomized 1,387 metastatic prostate cancer patients having their testes removed to receive either flutamide or a placebo to collect data.

* found that there was no significant difference in survival rates among the two groups, although blood levels of prostate specific antigen (PSA) fell in a greater number of patients who received the flutamide therapy.

* authors note that the findings also suggest that PSA levels may have no role as a market for survival in patients with metastatic prostate cancer.

In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, 29,133 men smokers were randomized to receive alpha-tocopherol 50 mg, beta-carotene 20 mg, both agents, or placebo for five to eight years. A total of 246 cases of prostate cancer occurred during the study, with 62 deaths.

Private Parts. An Owner's Guide to the Male Anatomy, 2nd Ed

Yosh Taguchi

McClelland & Stewart Inc, Suite 900, 481 University Ave, Toronto, ON M5G 2E9
1996/320 pp

Strengths

Easy to read, no-nonsense language, mostly accurate information

Weaknesses

Not always strongly evidence-based, sometimes too much emphasis on surgery, not patient-centred

This is Dr Taguchi’s second and updated edition of his “Canadian bestseller” first published in 1988. He is a well-known Montreal urologist who says he wrote this as “… the answer to all those questions I have ever been asked… in my office.” Further, as it says on the jacket, “Most men know more about their cars than about the workings of their own bodies.” Many family physicians would agree.

This book is a cleanly laid out, how-to manual for men who want to know more about their genitourinary system. The first chapter deals with basic anatomy and functions. The rest covers various problem areas, such as impotence (when will the medical establishment call this erectile dysfunction?), infertility, vasectomy, lumps, prostate problems, sexually transmitted diseases, and incontinence. The information is straightforward and accurate, and the last few pages contain commonly asked questions and answers.

The section on prostate problems is full of details on diagnosis and management. The author, however, gives too much information on surgical aspects, walking readers through every detail of how he performs the surgery. I also objected to the way routine prostate-specific antigen screenings and almost routine surgery (for prostate cancer) were encouraged. The evidence is still unclear about whether routine prostate-specific antigen screenings help, and no one will pass the College of Family Physicians of Canada’s (CFPC) examination if they push surgery for prostate cancer. I also believe the author makes too light of the quite high postoperative rates of erectile dysfunction. I have fewer points to criticize in the other sections. The details on STDs are good, and I liked the case reports in the section on lumps. This book might not pass the CFPC’s standard for patient-centred material; however, I recommend it as a practical book for patients and residents as long as their physicians read it first.

The leading test to detect prostate cancer is “clinically useless” at determining the size or severity of a man’s tumor, and is only of “limited” value at predicting cure rates from surgery to remove the diseased gland, a new study says.

The test, which measures a blood enzyme called prostate-specific antigen (PSA), is likelier to find benignly enlarged prostates and prompt overly aggressive treatment, according to the scientists who conducted the study.

The study, which appears in the January issue of the Journal of Urology, “is quite a disappointment,” says Dr. John McNeal, a Stanford University pathologist and a co-author of the paper.

“We used to think [PSA testing] was good. But what we would like it to tell us is whether a PSA that is not much elevated is elevated because of [normal prostate growth] or whether it’s elevated because of prostate cancer.” And the protein, at least at moderate levels, can’t do that, McNeal says.

Dr. Peter Albertsen, chief of urology at the University of Connecticut in Farmington, says the study “is not going to knock prostate-specific antigen (PSA) screening off the map by any means.”

However, Albertsen adds, PSA testing is undergoing a crisis of confidence similar to that of screening mammography, another exam whose value has come under questioning.

“I think there’s enough tantalizing evidence to think” that routine prostate-specific antigen (PSA) screening saves lives, Albertsen adds. But there’s not enough evidence to be sure.

Almost 190,000 American men are diagnosed annually with prostate cancer, and 30,000 will die from it, according to the American Cancer Society. Prostate-specific antigen (PSA) testing is widespread in men over age 50, but no study has proved that it saves lives by helping doctors identify prostate tumors when they’re still curable.

One reason: prostate cancer grows glacially. So while most men will die with cancer of the gland, relatively few will die of it. Aggressive treatment of slowly growing tumors may therefore cause more harm than good, some experts argue.

In the latest study, Dr. Thomas Stamey, a Stanford University urologist, and his colleagues studied the relationship between PSA scores in 875 men who underwent radical prostate surgery, in which the gland was completely removed, between 1984 and 1997.

Stamey’s group analyzed prostate-specific antigen (PSA) readings taken from many of the men both before and after their operation.

The largest tumors did produce extremely elevated PSA levels, topping 22 nanograms per milliliter of blood. Scores of more than 9 ng/ml were somewhat associated with aggressive disease, as measured by standard gauges of malignancy.

But for prostate-specific antigen (PSA) values between 2 and 9 ng/ml, the culprit was often not cancer but benign prostatic hypertrophy (BPH), or normal swelling of the gland.

Nor did PSA testing predict cure rates: Surgery success was the same for men whose pre-operation PSA was lower than 4 ng/ml as it was for those with a score of 10 ng/ml.

The prostate-specific antigen (PSA) enzyme is secreted by cells in the prostate, and mildly elevated values often reflect a larger than normal gland. BPH is as common as cancer, a fact many men don’t realize.

Scientists have been trying to tweak the prostate-specific antigen (PSA) test to make it more reliable, but whether these new techniques will be more sensitive to cancers remains a mystery. In fact, PSA is a misnomer, since the enzyme is secreted not only in the prostate but in the breast as well.

What To Do

Every man has a prostate-specific antigen (PSA) level, and any score between one and four could be totally normal, McNeal says. The tricky part comes in deciding what to do if the test comes back between 7 and 8. Despite his group’s findings, McNeal says he would probably undergo a biopsy if his own PSA test were in that range.

And saw palmetto berry extract, listed by Consumer Reports in the US as a potentially helpful herb, could be just what the doctor ordered.

As many as a third of all men over 50 may suffer from benign prostate hyperplasia, experts estimate. The condition is not cancerous and simply means that the tissue of the prostate is inflamed and swollen.

Saw palmetto berry extract can help the tissue to shrink, allowing for more regular urination patterns – and with few side effects, as long as you use it with a doctor’s help, experts say.

How does it work? No one is exactly sure, but herbalists have an idea.

“It seems to affect the hormone levels in the genital area,” says Kara Dinda, director of education for the American Botanical Council in Austin, Texas.

And while the effects of the herb on men’s prostates seem fairly well documented, its effect on women is not known. Since hormones may be affected, it’s especially important that pregnant and lactating women not use the herb.

Use of this herb, which derives from the berries of the dwarf palmetto tree which is grown largely in Florida, dates back to the 1700s among Native Americans. Rigorous studies supporting use of the herb are far more recent.

According to an article in the Minneapolis Star Tribune, for example, a 1996 study of 1,098 men in the US showed that saw palmetto berry extract is at least as effective as a popular prescription drug – and produces fewer side effects, including impotence. And The Daily Telegraph reports that close to 90 per cent of men in Germany with benign prostate hyperplasia are treated with plant extracts, and saw palmetto berry extract tops the list.

One concern among doctors has been that use of the herb or a product containing it might affect PSA levels, by which prostate cancer can be diagnosed. But an editorial in Urology said that US herb specialist Varro Tyler and a UCLA urologist showed that use of the herb did not affect any tests of the prostate, including the PSA.

Side effects? They’re relatively minor: stomach problems, headaches and, with large doses, diarrhea.

One caveat: A Boston Globe story reported that a 1998 review of the herb suggested that other new prostate medications may in fact be more effective than saw palmetto berry extract.

What To Do

This herb sounds promising. Men should ask their GP for further information, however. “Herbs produce chemicals,” says Erica Kipp, manager of the Plant Research Laboratory for the New York Botanical Garden. “I think people have the misconception that anything from a plant is natural and good and benign – and this is not necessarily the case.”

Dr. Ellis and Dr. John C. Blasko of the Seattle Prostate Institute led a course for fellow urologists at the annual meeting of the American Urological Association in Atlanta last week. They described the techniques used in brachytherapy and the criteria for selecting patients.

Usually, a urologist and a radiation oncologist work together to deliver this treatment, the doctors explained. The first step is a volume study in which ultrasound imaging through the rectum is used to measure the size of the prostate so the appropriate dose of radiation can be determined. With the patient carefully positioned, the ultrasound probe sends data to a computer program that digitizes the two-dimensional images and creates a three-dimensional reconstruction of the prostate gland.

After appropriate treatment has been determined, the implant itself takes place. The patient is positioned in exactly the same way as during the volume study, and receives an intravenous antibiotic while under either general or regional anesthetic. Needles containing the radioactive seeds are carefully positioned according to the coordinates determined by the software program. Usually, 25 to 35 needles, each containing two to six seeds, are used. Several imaging systems are used to make sure the seeds are implanted correctly.

Two factors taken into consideration when considering brachytherapy are the extent of the cancer — whether it has spread beyond the prostate — and its rate of growth. If cancer has spread outside the prostate, Dr. Ellis and Dr. Blasko explained, external beam radiation therapy (EBRT) can be used before the brachytherapy. EBRT covers the prostate, the seminal vesicles and the regional lymph nodes.

Another factor to consider before deciding on treatment is the size of the prostate gland. If it is too big, accurate needle insertion is more difficult and the increased number of seeds needed to treat it, may damage the urethra. Dr. Ellis and Dr. Blasko stated that hormone therapy can be used three or four months before brachytherapy to reduce the size of the prostate.

Like any treatment, brachytherapy can present risks and side effects. Complications can include urinary retention, inflammation and/or narrowing of the urethra, incontinence and proctitis (inflammation of the anus and rectum). The most serious of these is urinary retention — medications are often used before and after the brachytherapy to reduce the size of the prostate and improve urination.

Dr. Ellis and Dr. Blasko pointed out that although brachytherapy may cause more urinary irritation than surgery, it’s less likely to cause incontinence and impotence — two reasons it is becoming more popular in treating prostate cancer. Another reason is that the treatment can be done on an outpatient basis.

“It’s really unknown whether [the cause] is a small microbial agent such as a bacterium or virus, cytokines or autoimmune factors, toxins in the urine or some kind of oxidative stress. But there’s evidence of all of these, particularly psychological and immunological [factors],” according to Dr. Mark Samuel Litwin of the University of California at Los Angeles. Dr. Litwin addressed an audience of urologists at the annual meeting of the American Urological Association in Atlanta last week.

Litwin pointed out that “there is a tremendous psychological burden associated with this chronic condition.” Prostatitis can affect men of any age, but is most common among those between 35 and 50.

In the past, men with prostatitis were usually treated with antibiotics because it was assumed that the condition was the result of an often-unidentified bacterial infection. But Litwin explained that most cases are not caused by infection although sometimes signs of bacteria can be found if a urologist looks hard enough.

Antibiotics are less likely to be prescribed today, says Litwin, and there are other treatment options: alpha-blockers (such as Cardura, used to treat benign prostatic hyperplasia (BPH) and high blood pressure), non-steroidal anti-inflammatory drugs (NSAIDs), finasteride (Proscar — used to treat BPH), microwave therapy and even the drug allopurinol, used to treat urinary stones and gout.

Current practice involves a more thorough evaluation at diagnosis to look for any source of infection, Litwin stated. A urologist will massage the prostate and take a sample of the milky fluid it produces, and it will be examined for bacteria and for white blood cells. If signs of infection are present, antibiotics are prescribed. In most cases, though, there’s no sign of infection, and patients are prescribed NSAIDs and/or alpha-blockers as well as counseling and stress management training.

Litwin also noted that current research is looking into the usefulness of the new COX-2 inhibitors and bioflavonoids in treating prostatitis. In addition, the National Institutes of Health has recently funded a large collaborative study at six North American centers that will focus on basic research to understand prostatitis as well as clinical research to evaluate treatments.