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.

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.

First-Line Therapy

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.

Second-Line Therapy

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.

Emergency Management of disseminated intravascular coagulation (DIC) Syndrome

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.

Conclusion

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.

Prostate Specific Antigen (PSA) is blood test that is elevated in prostate cancer, benign prostate hypertrophy, prostate trauma, prostate infection, after prostate examination or ejaculation. Liver enzymes in blood can be elevated in many medical conditions. Some examples include viral hepatitis, medication effects, alcoholic liver damage, gallstone disease, cancer in the liver, excessive fat or iron in the liver etc. Therefore it is difficult to directly answer your question regarding relationship between elevated PSA and liver enzymes without more information.

Alkaline phosphatase is a liver enzyme that is also found in bone. Alkaline phosphatase can be elevated in liver disease and in bone diseases such as bone cancer and Paget’s disease of bone. In patients with prostate cancer that have spread to bone, both Prostate Specific Antigen (PSA) and Alkaline phosphatase can be elevated.

Thank you for your question!

Prostate-specific antigen has displaced prostatic acid phosphatase as the preeminent tumor marker for prostatic adenocarcinoma. The combination of several key features makes PSA unique among known tumor markers. It is remarkably sensitive to the presence of prostate cancer. Serum Prostate-Specific Antigen values are elevated in more than 95% of palpable cancers, including small palpable nodules (stage Bl lesions). Serum levels of Prostate-Specific Antigen are remarkably proportional to both clinical stage and pathologic stage found at radical prostatectomy. In fact, careful pathologic studies show that serum PSA is directly proportional to the volume of prostate cancer. Because the clinical and pathologic stages of prostate cancer, perhaps more so than any other malignant neoplasm studied, also appear to be a direct function of tumor volume, Prostate-Specific Antigen has proved a useful adjunct in staging. In untreated patients with prostate cancer who have undergone careful pathologic staging, it is almost unheard of to find regional lymph node metastases when serum Prostate-Specific Antigen levels are less than 10 µg per liter by the Yang assay (about 5.5 µg per liter by the more commonly used Hybritech assay). In untreated patients with serum PSA levels above 75 µg per liter by the Yang assay (50 µg per liter by the Hybritech assay), nearly two thirds have lymph node metastases, three quarters have seminal vesical invasion by cancer, more than four fifths will have extensive tumor volume and surgical margin involvement, and all will have high-grade lesions. Unfortunately, as with any biologic system — especially a deranged biologic system, which cancer is by definition — exceptional patients with high-volume prostate cancers and high serum Prostate-Specific Antigen values may have organ-confined disease, and patients with low-volume tumors and low PSA values may have early metastases. Also, because

Prostate-Specific Antigen is nonspecific for prostate cancer, serum levels may be elevated by coexistent prostatic disease, including bacterial prostatitis and benign prostatic hyperplasia. Therefore, although a valuable adjunct to our current clinical staging of patients with prostate cancer, measuring the PSA level does not eliminate the need for careful clinical assessment, including a digital rectal examination, technetium bone scans, and appropriate radiographic studies.

Prostate-specific antigen provides an excellent objective measure in observing patients with prostate cancer. Serum Prostate-Specific Antigen levels rise over time and correlate with clinical progression of the disease process in untreated patients with prostate cancer. Moreover, exponential increases in serum PSA levels usually precede clinical disease progression and may allow preemptive treatment planning. Any successful treatment of prostate cancer dramatically affects serum Prostate-Specific Antigen levels. In patients responding to androgen ablation, serum PSA levels fall precipitously, with nadir values typically reached by 3 to 6 months. After radiotherapy, Prostate-Specific Antigen values fall in a similar manner but with a more prolonged time course, and nadir values are reached at 12 to 18 months. Patients for whom either androgen ablation or radiotherapy fails also behave similarly, with exponentially rising serum PSA values usually preceding symptomatic clinical recurrence or progression.

One clearly defined use for Prostate-Specific Antigen is in observing patients after radical prostatectomy. These patients, if their cancer and prostate are completely surgically excised, should have no PSA in their serum. Given the serum half-life of the Prostate-Specific Antigen molecule (between 2.2 and 3.2 days), most patients should have zero serum PSA values by three weeks, and all should be zero by six weeks. The persistence or recurrence of Prostate-Specific Antigen in the serum after radical prostatectomy accurately predicts residual or metastatic cancer and usually presages clinical disease recurrence by many months or years.

We present a series of 31 men (mean age = 67 years; range = 48-82 years) who were referred to the urology unit over a 17-month period with a raised PSA, BPE on digital rectal examination, and a documented urinary tract infection (UTI). Five men were asymptomatic. The mean PSA (Hybritech Tandem-R PSA radioimmunoassay) at presentation was 24 ng/ml, with a range of 5.4-100 ng/ml (normal range = 0-4 ng/ml).

A clinically significant UTI (>10⁵ organisms per ml) was documented in all 31 patients. Following eradication of the urinary tract infection, the prostate specific antigen returned to normal (mean = 2.7 ng/ml; range = 0.3-3.9 ng/ml) in 81% of cases (25) within 17 weeks. In the remaining six cases, the PSA fell after treatment but remained persistently elevated above the normal range (9.7 ng/ml; range = 4-14.9 ng/ml). Eleven of the symptomatic cases became asymptomatic after treatment.

The failure of the prostate specific antigen to return to normal in six cases may be due to bulky benign prostate hyperplasia or an age-related variation in PSA. However, this group requires careful urological follow-up.

An uncomplicated urinary tract infection in men with benign prostatic enlargement appears to be the cause of an elevated PSA. Following eradication of the UTI, the prostate specific antigen normalizes in the majority of cases. The half-life of PSA is between 2.2 and 3.15 days. Estimation of the serum prostate specific antigen in men with benign prostatic enlargement on digital rectal examination with a suspected or documented urinary tract infection is therefore not recommended for a period of at least six weeks after successful antibiotic treatment. This will reduce the number of patients undergoing negative prostatic biopsies — a procedure not without an associated morbidity.

Simplified technology has made it feasible for most laboratories in Canada to assay prostate-specific antigen. Very little systematic information is available to suggest any uniformity across different geographic locations in the use of prostate-specific antigen. The volume of PSA testing has increased dramatically in most centres: the volume in our laboratory has doubled in 1 year, from about 250 per month in fall 1993 to 500 per month in fall 1994.

Two randomized, controlled trials are under way to provide the essential information on outcome measures. The European Cancer Program is supporting a study in which asymptomatic adult men will have an initial prostate-specific antigen test and then will be placed (randomly) in a control group or in a screening group in which digital rectal examination and transrectal ultrasound (TRUS) will be performed. The NCI is funding a similar multicentre, randomized trial in which the screening group will be tested with DRE and PSA every 3 years and, if either has abnormal findings, patients will be subjected to TRUS. Initial results from these trials will be available in about 7 years.

The natural progression of prostatic cancer is benign, though not universally so. Routine screening of asymptomatic men with prostate-specific antigen increases the detection rate of prostatic cancers that would not affect the longevity or even the quality of life of many men. However, faced with a diagnosis of cancer, most men opt for surgery or radiation therapy rather than take the chance that their cancer will not advance. In spite of improved surgical techniques, postoperative complication rates of impotence and urinary incontinence are high.

Wasson et al have reviewed the literature from 1982 to 1992 and give the following mean complication rates for total prostatectomy: incontinence 26.6%, impotence 85%, impotence following nerve-sparing surgery from two series 32%. Complication rates were slightly lower with radiation therapy. Most of these men (who had localized prostatic cancer) were symptom free, but must now live with complications for the rest of their lives. Chodak worked out the average mortality after radical prostatectomy (from reports published in academic centres) to be 1%, with a range of 0.5% to 3.0%.

Conclusion

Use of prostate-specific antigen for early detection of prostatic cancer is not supported by scientific evidence at present, and risk-to-benefit analysis is incomplete. If early detection of prostatic cancer is discussed during a periodic physical examination of a man between 50 and 70 years, some of these salient points should be brought up. If a decision is made to evaluate the prostate, do a PSA test and a digital rectal examination; if not, neither prostate-specific antigen nor DRE need be done.

Genitourinary symptoms and family history of prostatic cancer strongly indicate that a prostate-specific antigen test and a digital rectal examination should be done. If PSA levels are abnormally elevated, if patients have urinary symptoms requiring surgical evaluation, or if DRE findings are suspect, patients should be referred to urologists for further evaluation. ■

Cost per prostate-specific antigen test including labour is about $25. Even in a less populous province, such as Newfoundland, with about 50000 men between the ages of 50 and 75, annual screening would cost $1.25 million. This does not include additional costs arising from investigation of false-positive results. It is fair to state that mass screening for prostatic cancer with prostate-specific antigen is untenable.

Evaluating PSA as a screening test for diagnosing prostatic cancer is difficult because the natural history of prostatic cancer is largely unknown. When prostate-specific antigen is used in casefinding, very high rates of sensitivity and specificity are observed; Powell et al found in a group of men presenting with urinary obstruction a sensitivity of 90% and a specificity of 90%, using 10 µg/L as the cutoff value for prostate-specific antigen. In studies where PSA has been used to detect prostatic cancer in asymptomatic populations (screening), these figures are less impressive, with a false-positive rate of 67 % in one study.

Screening recommendations from professional groups

Neither the Canadian Task Force on the Periodic Health Examination (CTFPHE) nor the United States Preventive Services Task Force (USPSTF) advises routine testing for prostatic cancer; both base their recommendation on a formal appraisal of prevailing scientific evidence. The Canadian Cancer Society has not recommended screening with prostate-specific antigen. The National Cancer Institute (NCI) in the United States advises physicians:

Given the possibility of unnecessary morbidity associated with diagnosis and treatment of many such lesions, careful evaluation of prostate cancer screening is desirable. There is insufficient evidence to recommend transrectal ultrasound and serum tumour markers for routine screening in asymptomatic men.

Contrary to most cancer organizations in North America, the American Cancer Society recommends annual screening for all men older than 50 by both digital rectal examination and prostate-specific antigen. Both the American Urological Association and the Canadian Urological Association recommend annual screening for men 50 to 70 years with both DRE and PSA. The Canadian Urological Association’s recommendations were not accompanied by a presentation of supporting scientific evidence or of the process by which they were developed.

Casefinding for prostatic cancer is the responsibility of family physicians, and the two tests available to them are digital rectal examination (DRE) and prostate-specific antigen. The arbitrary threshold value of 4.0 µg/L for prostate-specific antigen is most frequently used to distinguish normal from abnormal values. Depending on tumour location, DRE has a false-negative rate of 50% to 60%. Larger, rapidly growing cancers with poor prognosis are most likely to be found by digital rectal examination. Studies have shown that DRE does not significantly increase rates of detection over prostate-specific antigen testing.

A limitation of prostate-specific antigen testing is that PSA levels are elevated during both benign and malignant diseases of the prostate. Three percent to 21 % of patients with BPH have PSA levels greater than 10 µg/L. Benign prostatic hypertrophy is far more common than prostatic cancer. Even among patients with PSA values of 11 to 23 µg/L, there are three benign prostatic hypertrophy patients to every two with prostatic cancer. On the other hand, 38% to 48% of patients with organ-confined prostatic cancer, the ideal candidates for therapy with the best chances of being cured, have prostate-specific antigen levels in the normal range. These figures emphasize the overlap in concentration of prostate-specific antigen in patients with benign prostatic hypertrophy and prostatic cancer. Bernstein et al, using Shannon entrophy calculations to determine optimum decision levels, concluded that 11 to 23 µg/L PSA levels are probably an equivocal region in which the frequency of BPH is about 1.5 times that of prostatic cancer. For older men, the long natural history of PC and the risks of surgery make total prostatectomy undesirable, thus removing most of the reasons for casefinding.

Diagnosis

Definitive diagnosis and treatment of prostatic cancer are the responsibility of urologists, to whom patients are referred because of urinary symptoms requiring surgical evaluation, suspect findings on DRE, or elevated serum prostate-specific antigen. A serious drawback of PSA is its lack of specificity for prostatic cancer, resulting in the need for further investigation of false-positive results with transrectal ultrasound (TRUS) and biopsy. Transrectal ultrasound is expensive and has limitations. Prostatic biopsy (the criterion standard) remains the confirming test for prostatic cancer, but is invasive and subject to error; detection rates for prostatic cancer range from 0.3% to 14.5%.

Background

Prostate-specific antigen, produced exclusively in the prostate, is a glycoprotein with a molecular weight of 30000 to 34000 daltons. Its function in the seminal fluid is to break down the seminal clot. Increased prostate-specific antigen production is observed in patients with benign prostatic hypertrophy (BPH), prostatic cancer (PC), and prostatis. In other words, PSA production increases as prostatic epithelial cells proliferate, benign or malignant causes notwithstanding. Serum prostate-specific antigen concentration increases with age. A study of 103 patients at a prostate clinic showed that only 11 % of men younger than 60 had a PSA level greater than 4 µg/L, whereas 40% of men older than 60 had a prostate-specific antigen level greater than 4 µg/L. The undisputed utility of PSA is in monitoring patients after prostatic cancer treatment with surgery, radiotherapy, or antiandrogen therapy. After radical prostatectomy, prostate-specific antigen should decrease to undetectable levels, ie, below the lower limit of detection of the assay used.

Prostate cancer

In Canada, prostatic cancer ranks second in frequency to lung cancer in men. It contributes to 27 000 potential years of life lost compared with 129000 years for lung cancer annually. Miller has ranked PC fourth based on incidence and death and ninth based on premature mortality (because the incidence of detected prostatic cancer increased later in life, so life-span is not shortened the way it is by cancers that develop in younger people and because many prostatic cancers progress so slowly that deaths from other causes supervene). The prevalence of prostatic cancer increases with age, as evidenced at autopsy.

The prostate is a walnut-sized, male sex gland located below the bladder and directly in front of the rectum. During intercourse, it produces a thick fluid that helps force sperm through the urethra and out of the penis. The prostate also produces PSA, an enzyme that liquefies seminal fluid permitting sperm to swim more freely. In the case of a healthy prostate, some of this prostate specific antigen leaks out into the bloodstream where it is either bound to blood proteins, or it is left “free” and unbound. According to recent research at the National Institute of Aging (NIA) and Johns Hopkins University School of Medicine, in cases of prostatic disease, including infection, prostate enlargement or cancer, increased levels of total PSA are readily detected in the blood. Elevated PSA readings would indicate the need for further diagnostic tests.

NIA and John’s Hopkins studies have shown that the rate of increase of total prostate specific antigen levels over time is one of the best predictors of prostate cancer. The ratio of free to total PSA can also predict whether prostate cancer is developing as well as its aggressiveness (i.e., whether it’s fast or slow growing). So when the time comes, remember your prostate specific antigen test – in the long run, your prostate might thank you.