Diagnostic events (in squares) in the sequence of screening and follow-up for prostate cancer. The size and darkness of the curved arrows indicate the current knowledge regarding diagnostic tools. Block arrows indicate the function of diagnostic modalities regarding the outcome of events.
Each year in the United States, 317,000 cases of prostate cancer are reported, with 41,400 men dying from it. About 50% of patients suffer from metastatic disease when they are diagnosed. These patients are treated with medical or surgical castration that may or may not involve antiandrogens. This first-line therapy has no effect on progression for 20% to 30% of patients. The remaining 70% to 80% experience relapse within the next three years and may qualify for second-line therapy options, which include cyproterone acetate, a synthetic antiandrogen steroid, and liarozole, the first retinoic acid metabolism-blocking agent.
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.
A recent analysis of the control arm of the Prostate Cancer Prevention Trial (PCPT) has revealed that 15.2% of men with a Prostate Specific Antigen (PSA) value less than 4 ng/mL had prostate cancer detected via prostate biopsy. Current recommendations suggest PSA levels lower than 4 ng/mL do not indicate clinically significant prostate cancer; thus, the study results are groundbreaking news because no prevalence data for this group of men was previously available.
The PCPT trial enrolled men older than 55 with a prostate specific antigen (PSA) value less than 3 ng/mL and an American Urologic Society (AUS) score below 20. The men in this trial were randomly assigned to receive finasteride 5 mg or a matching placebo daily and followed for seven years with annual PSA and digital rectal exam (DRE) screening, with 9,459 men assigned to the placebo arm. After seven years of PSA and DRE screening, the men who never had a PSA higher than 4 ng/mL, an abnormal DRE, prostate surgery of any type, and had a prostate biopsy (minimum of six samples) at the end of the study were evaluated for cancer prevalence. There were 2,950 men, ages 62 to 91, who met these criteria, and in 449 (15.2%) of those men, prostate cancer was detected. Always controversial, the use of the Analysis of the patient demographics revealed that age and race did not predict those who would have prostate cancer, but a positive family history (affected brother, father, or son) did correlate with an increased risk of prostate cancer (p = 0.004). The mean prostate specific antigen (PSA) score of men with cancer was 1.78 + 0.92 ng/mL, significantly different from those without cancer at 1.34 + 0.86 ng/mL (p = 0.001). The mean annual rise in PSA (0.32 to 0.46 ng/mL) was also significantly higher in men with prostate cancer (p = 0.001).
Since prostate specific antigen (PSA) was first described in 1979, the ability of the test to predict clinically significant prostate cancer has been hotly debated. What is a normal versus an abnormal PSA value; was the test sensitive and able to reliably detect it; and what would the costs be from false-positive results in patient harm and to society in unnecessary procedures performed? — all have been questioned over the past two decades. A prostate specific antigen (PSA) level higher than 4 ng/mL is the standard indicator for a man likely to have clinically significant prostate cancer. For men with a PSA level between 4 and 10, approximately 25% will have prostate cancer. For PSAs higher than 10, this number rises to nearly 50% of patients having prostate cancer detectable by biopsy.
Even with new data on the prevalence of prostate cancer in men with a prostate specific antigen (PSA) below 4, this information does not provide any additional direction on whom to treat. The finding that 15% of men with normal PSA values have early-stage prostate cancer requires the review of prostate screening practices, more importantly because the incidence of cancer likely to be aggressive (Gleason score greater than 7), although low at 2.3%, was sprinkled throughout the PSA distribution. Not all of these patients would undergo invasive therapy, because depending on the patient’s age and life expectancy, treatment may range from watchful waiting to prostatectomy for this stage of cancer.
What to do now? It was already known, based on autopsy studies, that 15% to 60% of men ages 62 to 91 had unrecognized prostate cancer.However, none of these men diagnosed at autopsy actually died of their cancer. Thus, what patients really need to know is what the best screening method is to ensure that men who undergo biopsies and other therapies are at risk for cancer-driven effects that will affect the length and quality of their life. While a small number of the cancers found in this study were aggressive based on their Gleason score, the low prostate specific antigen (PSA) values indicate a small volume of disease that is unlikely to imminently impact a patient’s quality of life. Further limitations of this study are that its results apply only to Caucasian men older than 62. The minimum age of these patients was 62, and minorities were poorly represented in the final sample. In the otherwise asymptomatic male with a PSA of 0 to 4 ng/mL, current recommendations still continue with close follow-up of AUS score, digital rectal exam (DRE), and prostate specific antigen (PSA) to guide definitive therapy if indicated in that specific individual. The information from this study further emphasizes the critical need for patients’ annual follow-up with their oncologist or urologist to facilitate medical interventions if and when they are needed. Meanwhile, new biomarkers and stratification schema are being pursued as oncologists work to further define better diagnostics and care algorithms in the treatment of those with this challenging disease.
A new report suggests that the antioxidant vitamins C and E appear to counteract some of the negative effects of male hormones (androgens) on prostate cells linked to the development of 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
Effect on Survival Rate of Metastatic Prostate Cancer Patients
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.
A new study concludes that men treated with the drug flutamide after surgical castration for advanced metastatic prostate cancer have poorer qualities of life, compared to patients not taking the drug.
* researchers at the Fred Hutchinson Cancer Research Center, in Seattle, Washington, studied more than 700 prostate cancer who were castrated to reduce testosterone levels to collect data.
* found that those patients post-operatively treated with flutamide reported higher levels of diarrhea and mental health problems after three months, compared to patients taking a placebo.
* authors further note that, in agreement with another recently- published study, no survival benefit was found among those treated with the drug after castration, compared to those given a placebo.
In the Journal of the National Cancer Institute (1998; 90: 440-6), researchers report that long-term supplementation with alpha-tocopherol reduced prostate cancer incidence by 32% and mortality by 41% in men who smoked. In men who took beta-carotene, cancer incidence was 23% higher and mortality 15% higher than in those receiving placebo.
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.
Seller of cancer therapies becomes a patient with a success story
Cancer has been a part of Don Mills’ life for 17 years, but it was only in the last year that it threatened him with death.
Mills sold radiation therapy systems for Varian Medical Systems Inc. for almost two decades, traveling to cancer centers across the United States. While waiting for sales appointments, he often sat alongside cancer patients.
“I can’t tell you how many times I’d say a little prayer, ‘Please, don’t let me be sitting here for anything other than just selling something,’ ” Mills recalls.
But when he was diagnosed with the disease, he decided to take a chance on something new in his field: Intensity Modulated Radiation Therapy (IMRT), which targets tumors more accurately and intensely than conventional radiation. Doctors say others could soon benefit from this approach.
“IMRT is certainly coming into vogue. It’s the most recent thing that’s out there for radiation oncologists,” says Dr. Scott McGinnis, a radiation oncologist in Charlotte, N.C.
Mills’ story began in April 1999, when he had his annual physical. It included a prostate specific antigen (PSA) test, which his doctor had started doing seven years earlier because of a family history of prostate cancer.
This test found Mills’ PSA had shot up by a factor of almost three. He went to a urologist. Two of six biopsies showed malignant cancer.
The irony was not lost on Mills, and there was a more visceral response.
“I was very angry,” says Mills, who was 50 at the time of the diagnosis.
A devout runner since high school, the Colorado Springs, Colo., resident pounded 25 to 30 miles of pavement a week. He never smoked and watched his diet. That’s why Mills harbored a sense of betrayal – his body hadn’t held up its end of the bargain.
“I always thought that with my running and my lifestyle, I’m immune to cancer. I’ll live to a ripe old age and die in my sleep. So I was pretty angry about it. I thought, ‘Why me?’ but I figured it was God’s plan. I can’t question that. I don’t agree with it, I don’t like it, but I’ll deal with it,” Mills says.
Once over the initial shock and outrage, Mills plunged into researching his options. He says it wasn’t a given he’d choose radiation treatment just because he sells radiation therapy systems.
“Believe it or not, even though I work for a company that sells this equipment and was very familiar with that, it was not a slam dunk that that’s what I was going to do,” he says.
Mills was overwhelmed by what he discovered.
“I found out I really wasn’t as knowledgeable as I thought I was about this disease. When I started researching it and looking into it, the thing that really bothered me was the amount of options available,” Mills says.
They included surgery, different kinds of radiation treatments and watchful waiting.
“After about two weeks of looking at these things, I became extremely frustrated that there was no clear winner, as such. Some had terrible side effects or long-term rehabilitation, and some had some very negative quality-of-life issues associated with them,” Mills says.
After more research and consultations with medical friends and colleagues, Mills chose Intensity Modulated Radiation Therapy (IMRT). It uses computer-generated images to match a radiation dose to the shape of the tumor, while avoiding more of the healthy tissue.
Because of its precision, IMRT allows for higher doses of radiation, quicker treatment and fewer complications.
“I want to point out that it’s important for each individual to come to their own conclusion. What worked for me, what I felt was best for me, may not be best for other individuals,” Mills says.
He started his nine-week treatment at Memorial Sloan Kettering Cancer Center in New York City in last September. Each day he’d go for his treatments, which lasted about 10 minutes each.
Mills kept running and doing some work during his cancer therapy. He’d run six miles a day at dawn through Central Park and go to therapy later. Not having to hang up his running shoes was a boost to his mental and physical well-being, he says.
He says he feels Intensity Modulated Radiation Therapy (IMRT) will change the face of radiation oncology.
“If you can lower the healthy tissue dose and raise the dose to the tumor, you’re going to cure a lot more people. You’re also going to lower the complication rate. People feel better and they can continue their lives as near-normal as they can,” Mills says.
“All the different companies are now promoting these computer-operated systems for different radiation therapy centers to use,” McGinnis says. “So people are starting to incorporate them into their daily practices. It’s still very new.”
“It has to get in and be used, and people have to feel comfortable with the results they get before it becomes mainstream. So I think it’s probably several years down the road before it will be mainstream,” McGinnis says.
Ketoconazole – Nizoral, Extina, Xolegel, Kuric
Prostate cancer is the most common malignancy in American males above age 55. The cause of prostate cancer is not known. The most accepted risk factors are age, race and family history. Common signs and symptoms include dysuria, urethral obstruction, back or hip pain, and complications of advanced metastatic disease such as spinal cord compression and disseminated intravascular coagulation (DIC) syndrome.
The American Urological System of staging prostate cancer designates four stages of tumor growth, A through D, with each stage containing substages. Stage A is occult, nonpalpable; stage B is palpable, macroscopic tumor; stage C is tumor with extracapsular extension, but still clinically localized; and stage D is metastatic disease. The management of prostate cancer is greatly influenced by the stage of the disease but also by the patient’s age, physical condition, and response to prior therapy. Traditionally, prostatectomy or radiation therapy is considered for patients with stage A or B disease and hormonal therapies that suppress the body’s production of androgens have been a standard treatment for selected patients with stage C or stage D disease. In the past decade, however, studies have been suggested that earlier initiation of hormonal therapy for patients with early forms of metastatic disease may prolong disease-free survival and overall survival.
Androgens play an important role in promoting the growth of the prostate glands and about 80% of stage D prostatic tumors are androgen dependent. The hypothalamus secretes luteinizing-hormone-releasing hormone (LHRH) which in turn signals the pituitary gland to release luteinizing hormone (LH). Luteinizing hormone causes the testes to synthesize androgens, such as testosterone. After it is secreted by the testes, testosterone is metabolized into dihydrotestosterone (DHT) which then binds to its receptor to stimulate testicular protein production, cell division and growth. About 95% of testosterone is synthesized by the testes and the remaining 5% is released by the adrenal glands. The goal of hormonal therapy is to stabilize the disease or to provide regression, and this can be achieved by reducing testosterone to castrate level (<50 ng/mL). The most common hormonal therapies include bilateral orchiectomies, estrogen (e.g., diethylstilbestrol), LHRH agonists (e.g., leuprolide, buserelin, goserelin), progestins (e.g., megestrol acetate) and antiandrogens (e.g., flutamide, cyproterone, bicalutamide). The onset of action of these agents may take up to two weeks. It has recently been shown that ketoconazole can lower testosterone concentration to castrate levels within 48 hours. This prompt therapeutic onset of action has led to the investigation of ketoconazole as an antiandrogen agent.
Ketoconazole can lower testosterone concentration to castrate levels within 48 hours. Many studies show the agent inhibits two CYP450-dependent enzymes to block testosterone synthesis.
Ketoconazole is an imidazole antifungal agent. The antiandrogenic effects of this drug in mammalian cells were detected after the development of gynecomastia in some patients treated for fungal infections. Thereafter, many studies showed ketoconazole blocks the synthesis of testosterone by interfering with the cytochrome P-450-dependent enzymes of steroid biosynthesis. In the testes and the adrenal glands, cholesterol is converted to pregnenolone and progesterone. Both pregnenolone and progesterone are then transformed by a series of enzyme-controlled steps to dehydroepiandrosterone, androstenedione, and testosterone. Two cytochrome P-450-dependent enzymes, the 17-hydroxylase and the C17-20 lyase, catalyze this conversion. Ketoconazole inhibits both enzymes resulting in reduction of testosterone levels to reach castration levels in men.
Trachtenber et al. examined the effects of oral ketoconazole 400 mg every 8 hours on 15 patients with advanced prostatic cancer.Two patients withdrew: one for personal reasons and one developed a paraspinal mass. Thirteen patients completed the study.After three days of therapy, the need for analgesics was greatly reduced in all patients. The mean serum testosterone concentrations decreased to near anorchid concentration. After six months of therapy, 13 patients were in remission and side effects of the drug were minimal. This study showed that ketoconazole was effective and well-tolerated.
In a study conducted by Aabo et al., the effect of ketoconazole was examined in 11 previously untreated prostatic cancer patients. High-dose ketoconazole 400 mg every 8 hours was reported effective in inducing complete response (elimination of pain and tumor cells) in two patients and partial response (reduction of pain, recalcification of osteolytic bone lesions) in four patients. The most common adverse reactions were nausea, anorexia and hypertension. A rebound increase in testosterone levels developed in five patients. The investigators concluded that adverse reactions and rebound increase in testosterone levels limit the use of high-dose ketoconazole as first-line therapy in advanced prostate cancer.
Cersosimo et al. reviewed a number of small studies in which ketoconazole 400 mg was given every 8 hours to a total of 88 patients. Complete and partial remissions were achieved in three and 15 patients, respectively. Adverse reactions included nausea and vomiting (33%), impotence, gynecomastia (10-15%), dry skin, elevation of hepatic aminotransferases and occasionally severe hepatitis.
Almost all patients will eventually no longer respond to conventional androgen deprivation therapy (orchiectomy, estrogens, LHRH agonists, etc.) and relapse. This syndrome has been termed the “antiandrogen withdrawal syndrome.” Recent reports have suggested that, in these situations, the administration of ketoconzole may be of some benefit. The rationale behind this therapy is based on the hypothesis that, after testicular castration, adrenal androgens play a significant role in prostatic tumor cell stimulation. Ketoconazole inhibits both testicular and adrenal androgenesis. Therefore, it can provide further androgen ablation.
Witjes et al. examined the efficacy of oral ketoconazole 400 mg every 8 hours or 600 mg every 12 hours daily in 28 patients. All patients had relapsing metastatic prostatic disease that was initially responsive to hormonal therapy. At the end of nine months of treatment, 13 patients died from metastatic disease. Nine patients withdrew: seven because of gastrointestinal (GI) side effects and two due to progressive disease. One patient was unevaluable. Five patients remained in the study: four were objectively stable and one had progressive disease. The clinical and biochemical results in both treatment regimens (400 mg every 8 hrs., 600 mg every 12 hrs.) were similar. Serum ketoconazole concentrations were within therapeutic levels (at least 4 µg/mL to achieve testosterone concentration within the castrate range) at 8 hrs. (400 mg every 8hrs. group) and 12 hours (600 mg every 12 hrs. group) after last ketoconazole intake. All five patients completed the study and were reported to be pain-free (required no analgesics). This study suggested that ketoconazole may be beneficial in the management of patients with relapsing metastatic prostate cancer. However, side effects of the drug may limit its use. Further studies are needed.
Small et al. studied the activities of ketoconazole in 50 patients who were refractory to flutamide and had progressive disease after flutamide withdrawal.Results of the study showed 30 patients had greater than 50% decrease in prostate specific antigen (PSA). The most common toxicities were GI upset, fatigue, edema, hepatotoxicity and rash. It was concluded that ketoconazole retained significant activity in patients who were refractory to antiandrogen therapy.
About 24% patients with prostatic cancer develop life-threatening disseminated intravascular coagulation syndrome, which requires emergency correction of the underlying disease. The triggering mechanism of this syndrome is due to the release of tissue factor by tumors into the circulation and activation of the coagulation cascade. This hypercoagulable state results in hemorrhage, thrombotic and embolic complications. Lowe and Somers reported the successful use of ketoconazole 400 mg every 8 hours in a 72-year-old black man with prostate cancer. Spontaneous bleeding from DIC stopped within 48 hours. Litt et al. also reported a similar case in an 84-year-old prostatic cancer patient. Ketoconazole 400 mg every 8 hours successfully reversed DIC syndrome in this patient after four days treatment and an orchiectomy was subsequently performed.
Ketoconazole inhibits the synthesis of androgens in both the testes and the adrenal glands by interfering with cytochrome P-450 enzymes. An effective dose appears to be 400 mg every 8 hours. At this level, the drug produces castrate levels of testosterone within 48 hours, produces subjective (e.g., significant pain relief) and objective (e.g., decrease in PSA levels and recalcification of osteolytic bone lesions) improvement in patients who have advanced prostate cancer. However, high incidence of adverse effects, such as severe GI intolerance, hepatic toxicity, impotence and gynecomastia may limit its routine use in this disease. Other disadvantages of ketoconazole include its short half-life that requires every-8-hour administration. Addisonian crises can occur in high-dose ketoconazole therapy and supplementation of dexamethasone may be necessary. Finally, rebound elevation of serum testosterone will occur after long-term (3–6 months) therapy.
Because of all these problems, ketoconazole is currently considered for a limited number of indications. Its major usefulness is in the group of patients who need a prompt therapeutic response, such as in disseminated intravascular coagulation (DIC) syndrome with advanced prostate cancer. It is an excellent modality for short-term use when orchiectomy, surgical or medical, or other forms of therapy, such as estrogens, are contraindicated. Finally, it can be used as initial empiric therapy to obtain prompt clinical relief during the diagnostic workup when prostate cancer is suspected. The role of ketoconazole in the treatment of patients with hormonal refractory disease has yet to be determined.
PSA test doesn’t detect tumor’s severity, Stanford University study says
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.
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.
