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The Smilow Center Approach to Prostate Cancer Screening and Biopsy

Below you will find answers to frequently asked questions about prostate cancer screening and biopsy, answered by Smilow Center physicians.

Should I undergo PSA screening?

There is a great deal of controversy about the risks and benefits of prostate cancer screening. Those who embrace screening argue that prostate cancer is the second leading cause of cancer-related deaths among American men and that early detection and treatment is the explanation for the 40% reduction in the mortality rate from this cancer (Catalona WJ, N. Engl. J. Med. 361:204-205). Those opposed to prostate cancer screening argue that, in many cases, screening identifies cancers that, if undetected, would never cause harm, thus exposing men to unnecessary treatment, with its inherent risks (Welch HG, Albertsen PC. J. Natl. Cancer Inst. published online 31 August 2009).

The choice is a difficult one. If we abandon screening, prostate cancer will remain the second leading cause of prostate cancer death, and many men will die a painful (and preventable) death. On the other hand, if we aggressively screen and treat every man, many will suffer unnecessary complications of treatment.

The physicians of the Smilow Comprehensive Prostate Cancer Center believe that prudent prostate cancer screening will reduce prostate cancer mortality. Not all cancers need immediate or aggressive treatment. At the Smilow Center, we are committed to assessing the risk of the individual cancer and understanding the concerns, goals and priorities of the individual patient, and then offering each patient an array of appropriate treatment options. Using this approach, the Smilow Center will maximize the benefits and reduce the risks of prostate cancer screening.

The Smilow Center believes that all men over the age of 50 who have a life expectancy of more than 10 years should undergo annual prostate cancer screening, in the form of an annual digital rectal examination (DRE) and prostate-specific antigen (PSA) blood test. Men with a family history of prostate cancer and African American men should initiate annual screening at age 40. Smilow Center physicians believe that it is prudent for all men to obtain a PSA at age 40, and if the level is less than 0.6 ng/ml, the test should be repeated every three to five years until the age of 50. If the PSA is >0.6 ng/ml, men should have yearly PSA testing thereafter.

The decision to screen or not to screen for prostate cancer is often at the discretion of both the primary care physician and the individual. In the United States today, the overwhelming majority of men over the age of 50 years have undergone PSA testing. Men rarely come to the Smilow Center for initial prostate cancer screening. In many cases, men are referred to the Smilow Center with an elevated PSA or abnormal DRE, and their first question is, "Do I need a prostate biopsy?"

Do I need a prostate biopsy?

The decision to recommend a prostate biopsy should not be based on any one factor alone. At the Smilow Center, our goal is to provide an individualized prostate cancer risk assessment to determine if a prostate biopsy should be performed. Reasons for recommending a prostate biopsy may include an abnormal digital rectal exam (DRE) and/or an elevated or rising prostate-specific antigen (PSA) level. Other factors that come into consideration are age, overall health, longevity, ethnicity and family history of prostate cancer. Several risk ‘calculators’ or models have been proposed for deciding if someone needs a biopsy. None seem perfect, but they do take into account the many factors which might influence PSA. Smilow physicians have been active in evaluating the performance of such models in efforts to define the best one (Hernandez DJ, Han M, Humphreys EB, Mangold LA, Taneja SS et al. BJU Intl. 103(5):609-14 (2009)).

Digital rectal exam. The digital rectal exam is a method by which a urologist feels the surface of the prostate through the rectal wall in order to identify areas that are asymmetrical or abnormally firm. Any of these findings may suggest a prostate cancer and should usually be followed by a biopsy, regardless of the patient’s PSA level. In many cases, the prostate is enlarged due to benign prostatic hyperplasia (BPH). It is very important to note that benign enlargement of the prostate alone is not indicative of prostate cancer. Men naturally develop enlargement of the prostate as they age, and while this can cause difficulty urinating, it is not associated with prostate cancer. Enlargement of the prostate over time is no more abnormal than gray hair or wrinkles.

PSA test. PSA, or prostate-specific antigen, is a circulating protein in the bloodstream that is produced exclusively by prostate tissue and can be measured by a simple blood test. At the Smilow Center, we believe that the higher the PSA level, the greater the probability of a prostate cancer.

The PSA level is affected by a multitude of factors, so an elevated PSA alone does not always mean cancer. PSA readings are affected by the size of the prostate, the presence of urinary tract infection or prostate infection, nonspecific inflammation of the prostate and manipulation of the prostate following urinary catheter placement, cystoscopy or even colonoscopy. It is likely that a number of other unknown factors may also influence serum PSA.

Using the serum PSA to guide decisions about prostate biopsy has come under fire for a number of reasons. First, some urologists believe that biopsy on the basis of PSA alone will identify a large number of slow-growing, early prostate cancers that represent do not represent an immediate or long-term threat to survival. The flip side of the argument is that ignoring the PSA or not checking it may result in missing a very aggressive prostate cancer. As a result, Smilow Center physicians continue to advocate the use of serum PSA for early prostate cancer detection. Careful interpretation of the PSA results is crucial, since not every elevated or rising PSA is cause for a prostate biopsy. A patient’s age, ethnicity, family history, prostate size and previous PSA measurements must be taken into account to allow appropriate recommendations for prostate biopsy.

What is a ‘normal’ PSA level?

In the past, PSA was thought to be abnormal if the level was higher than 4 ng/ml. When men with a PSA over 4 ng/ml undergo a prostate biopsy, the risk of finding cancer is about 35%–40%. A PSA under 4 ng/ml was thought to be within ‘normal’ range, and a biopsy was not recommended for these men unless the DRE was abnormal.

Subsequently, it was observed that a number of men with PSA between 2.5 ng/ml and 4 ng/ml also had cancer (Catalona WJ, Smith DS, Ornstein DK. JAMA 277:1452-1455 (1997)). About 20–25% of men with PSA in this range were ultimately found to have cancer upon biopsy. More recent studies have demonstrated that even among men with a PSA as low as 1 ng/ml, one out of ten are found to have prostate cancer upon biopsy (Thompson IM et al. N. Engl. J. Med. 350:2239-2246 (2004)).

It is important to note that many of the cancers detected by PSA screening would not eventually cause death if they went untreated. Based on these observations, a single PSA cutoff is no longer used to define ‘abnormal’. Depending upon your age, ethnicity, family history and the recent changes in your PSA, the Smilow Center may recommend a biopsy for PSA levels less than 4 ng/ml. Conversely, we may recommend against a biopsy for some men with levels higher than 4 ng/ml.

What is a free PSA level?

In the blood, PSA can circulate alone (free) or bound to other proteins (complexed). It is by measuring both the free and complexed forms of PSA that a total PSA, the number most commonly ordered as a first test, is determined. In men with an elevated or concerning PSA level, breaking down the PSA into free and complexed forms can give more information about the risk of cancer. In all men, the majority of PSA circulates in the complexed form, but in men with prostate cancer, more PSA on average is complexed than in men without prostate cancer. As such, a lower free PSA, or a lower free-to-total PSA ratio, is more suggestive of cancer than a high free-to-total ratio.

The free-to-total ratio is the most common method by which free PSA is reported. It is generally felt that a ratio of greater than 25% is reassuring, 15-25% is suspicious and below 15% is very suspicious for cancer. Smilow Center physicians have been active in evaluating free and complexed PSA in their prediction of prostate cancer (Taneja SS et al. Urol. 60:10-17 (2002); Horninger W, Cheli CD, Babaian RJ, Fritsche HA, Lepor H, Taneja S, et al. Urol. 60:31-35 (2002); Naya Y, Stamey TA, Cheli CD, Partin AW, Sokoll LL, Chan DW, Brawer MK, Taneja SS, Lepor H et al. Urol. 60:36-41 (2002); Partin AW, Brawer M, Bartsch G, Horninger W, Taneja SS, Lepor H et al. 170:1787-91 (2003); Naya Y, Fritsche HA, Cheli CD, Stamey TA, Bartsch G, Brawer MK, Childs S, Taneja SS, Lepor H et al. Urol. 62:1058-62 (2003)). It does not appear that free PSA alone is always helpful. This may be, in part, due to the fact that it is rapidly degraded, even in the refrigerator. As such, if your blood sits around for a long time before measurement, your free PSA, and total, may be lower. At the Smilow Center, we take into account the free PSA in addition to a number of other clinical factors including age, prostate size, presence of infection, in deciding if a prostate biopsy is warranted.

Should I take antibiotics to see if the PSA rise is due to infection?

An infection in the prostate is one potential cause of an elevated PSA. Symptoms of prostate infection may include burning upon urination, frequent urination, difficulty in passing urine, fever, chills, or pain in the bladder, testicles, lower back or perineum. In the absence of these symptoms, it is unlikely that an elevated PSA is due to infection.

Many urologists prescribe antibiotics to see if the PSA level drops, but it is often difficult to know if an observed decline in PSA is due to the antibiotics or simply due to variations in the PSA. Therefore, unless the PSA drops by a great deal, a biopsy is usually still required. At the Smilow Center, our approach is to evaluate patients carefully for infection. If none of the symptoms of infection are present, we would usually not recommend a course of antibiotics in an attempt to lower the PSA.

My PSA tripled over the last 6 months. Does this mean I am going to die of prostate cancer?

There is substantial evidence that the rate of increase of the PSA (or the doubling time) predicts the likelihood of death from prostate cancer in men undergoing treatment. However, there is also evidence that the rate of rise prior to prostate biopsy predicts the aggressiveness of a cancer.

It is important to note that infection is a more common cause of very rapid PSA doubling time than prostate cancer. So, a tripling of the PSA level in 6 months most likely does not mean that you are going to die of prostate cancer, but it does mean that you need careful observation.

Is there anything I can do to reduce my PSA? Will reducing my PSA reduce my risk of cancer?

5-alpha reductase inhibitors (5-ARIs) such as finasteride (Proscar) and dutasteride (Avodart) have been shown to reduce the size of benignly enlarged prostates. Shrinking the prostate results in both the improvement of urinary symptoms and the prevention of acute urinary retention (a complete blockage of the passage of urine). The reduction in prostate volume following the use of 5-ARIs is associated with a 50% reduction in the PSA level.

More recently, 5-ARIs have been shown to reduce the risk of developing prostate cancer by roughly 25% (Thompson IM et al. N. Engl. J. Med. 350:2239-2246 (2004)). The Smilow Center has incorporated the use of 5-ARIs to reduce the risk of developing prostate cancer.

There is also some evidence that diets very low in fats, natural products and other dietary modifications and some natural products may also lower the PSA.

At the Smilow Center, we do not feel that steps should be taken to lower the PSA prior to prostate biopsy. Once the biopsy results are known, steps to lower the PSA with the intent of preventing prostate cancer may be taken once the biopsy results are known.

Can an imaging study (MRI or color Doppler ultrasound) take the place of a prostate biopsy?

Prostate imaging has improved dramatically in recent years. Urologists and radiologists working collaboratively at the Smilow Center are defining novel techniques to improve diagnostic imaging of the prostate. We are now able to see small areas of cancer that would have previously gone unnoticed. Despite this, no imaging study today can replace the need for a prostate biopsy.

At the Smilow Center, we regularly use prostate MRI both to evaluate men who have already been diagnosed with prostate cancer and to determine if we have missed a cancer in men who have a negative biopsy but a very suspicious PSA. Color Doppler ultrasound and other forms of imaging are used to guide biopsy needles to the most suspicious areas in the prostate (‘targeted’ or ‘smart’ biopsy). Although these tests enhance the sensitivity of detection (the ability to find potential sites of cancer), they do have a high likelihood of false positives, so abnormal findings resulting from imaging studies must be confirmed with a biopsy.

Is my benign enlargement of the prostate causing the PSA to be elevated?

Benign enlargement of the prostate is a potential cause of PSA elevation. This is because benign prostatic tissue is capable of producing PSA. An elevated PSA in a man with a very large prostate is of less concern than the same PSA in a man with a smaller prostate. Nonetheless, even men with large prostates and a slightly elevated PSA are at risk for prostate cancer. A large prostate alone does not rule out the need for a biopsy.

When interpreting the PSA, Smilow Center urologists will take prostate size into account by calculating the PSA density (PSA divided by prostate volume). A higher PSA density is indicative of prostate cancer, while a lower density suggests a benign enlargement. At the Smilow Center, we use the PSA density to monitor patients with negative biopsies and men on active surveillance protocols (Taneja SS, Tran K, Lepor H. Urol. 58(2):222-6 (2001)).

What rate of increase in PSA will trigger a biopsy?

As men age, their PSA levels will typically rise due to progressive enlargement of the prostate gland. Since the normal prostate makes PSA, the PSA level will continue to rise very slowly as the prostate grows. The acceptable rate of increase has been controversial over the years, and it remains unclear. Early investigations based on the Baltimore Longitudinal Study of Aging demonstrated that men whose PSA rose more than 0.75 ng/dl per year were more likely to develop prostate cancer in follow-up. However, because the study was not primarily intended to evaluate risk of prostate cancer, not all men were biopsied.

More recent studies of men followed within a prostate cancer screening study suggest that a PSA rise of more than 0.4 ng/dl per year may be suggestive of cancer (Loeb S, Roehl KA, Catalona WJ, Nadler RB. J. Urol. 177(3):899-902 (2007); Loeb S, Roehl KA, Nadler RB, Yu X, Catalona WJ. J. Urol. 178(6):2348-52 (2007); Taneja SS. Eur. Urol. 52(2):607 (2007)).

How is a prostate biopsy performed?

A prostate biopsy is performed by sampling the prostate tissue through the rectal wall under the guidance of a transrectal ultrasound probe. The procedure is typically performed with the patient awake, without intravenous sedation. Local anesthesia is placed around the prostate nerves with transrectal ultrasound guidance. The urologist places an ultrasound probe slightly larger than a finger into the rectum to visualize the prostate. Areas suspicious for cancer in the prostate, seen as dark regions on the ultrasound, are directly biopsied. In cases without any obvious abnormality noted on ultrasound, the prostate is sampled systematically in 12 locations. Smilow Center surgeons often use Power Doppler ultrasonography to help identify regions in the prostate with abnormally high blood flow. This is often a sign of a more aggressive prostate cancer.

Abnormal regions of the prostate identified by this technique can be targeted for additional biopsy samples. In a conventional biopsy, the urologist selects individual sites based on their location in the prostate. At the Smilow Center, we are developing new methods of biopsy in which more reproducible templates are created by computerized methods. A Smilow Center physician recently led a national study evaluating the effectiveness of the TargetScanTM computerized template biopsy (Taneja SS. Rev. Urol. 8:173-182 (2006); Megwalu II et al. BJU Int. 102(5):546-50 (2008)).

Immediately before the biopsy, a local anesthetic is injected around the prostate to numb the nerves providing sensation. This anesthetic doesn’t remove sensation altogether, but it should remove the sensation of pain during the biopsy, much as in a dental procedure. Biopsies are obtained using a hollow needle directed into the prostate by a spring-loaded gun. When the needle returns, it carries a thin core of prostate tissue that can be evaluated by the pathologist.

How many specimens are typically obtained during a prostate biopsy?

Traditionally, a transrectal ultrasound guided biopsy included six cores taken from the base, midzone, and apex of the right and left prostate. In addition to having a low yield of detection, a major problem with six-core biopsies was that they did not adequately exclude cancer. When a man had a negative six-core biopsy, he had a 20%–25% likelihood of a missed cancer. In 1998, a Smilow Center physician was the first to describe the routine use of 12 cores rather than six (Levine MA, Ittman M, Melamed J, Lepor H. J. Urol. 159(2):471-5 (1998)). This allowed for the detection of more prostate cancers, with fewer false negatives. The use of 10 to 12 cores has now become a national standard of care to provide an acceptable false negative rate, thereby reducing the need for repetitive negative biopsies.

The number of cores may vary in special circumstances. If an abnormality is seen on ultrasound or by a Doppler study, additional cores may be taken from that specific site. At the Smilow Center, additional cores are obtained in men with very large prostates, to ensure adequate sampling. Finally, in cases of high suspicion, Smilow Center urologists may take additional samples from the transition zone (the area of the prostate surrounding the urethral tube as it courses through the prostate). Although few cancers arise from the transition zone, occasionally this can be a site of missed cancers. At the Smilow Center, we do not routinely obtain transition zone samples for diagnosis, but we do sample this region for men undergoing repeat biopsies, men with very high PSA, men with precancerous changes in the prostate and men who are potential candidates for surveillance.

How much pain is experienced during a prostate biopsy?

Pain may occur at two points during a prostate biopsy.

First, at the time of probe insertion, men may experience discomfort from the stretch of the anal sphincter. In particular, men with hemorrhoids, anal fissure or rectal strictures may experience pain. This can be minimized by generous use of lubrication and lidocaine jelly, a local anesthetic.

The second point is when the biopsy needles are directed into the prostate. Prior to the biopsy, a local anesthetic is administered around the prostate to numb these nerves providing the painful sensation. The anesthetic doesn’t remove sensation altogether, but rather removes the sensation of pain during the biopsy, much as in a dental procedure. While pain thresholds are very different for every man, prostate biopsy is extremely well tolerated by most men. On occasion, if an individual cannot tolerate probe placement, a biopsy can be rescheduled under general anesthesia or deep intravenous sedation. Because this is uncommon, at the Smilow Center we always start with an ‘awake’ biopsy.

What are common complications of prostate biopsy?

In general, prostate biopsy is extremely safe. Men are likely to experience small amounts of bleeding from the rectum or urethra (urinary tube) for a few days after the procedure. The ejaculate (semen) may be discolored by blood intermittently for several weeks. This is not harmful to the patient or to his partner. In fewer than 1% of biopsies, bleeding from the rectum may be severe, with passage of clots or large amounts of blood. If this occurs, men should be seen in the emergency room for evaluation, and they may require intervention to control bleeding. In most cases, even severe rectal bleeding will subside on its own.

Infection is a rare complication of prostate biopsy. Infection may result in burning during urination, progressive difficulty urinating, and pain in the low back, testicles, anus or perineum within days or weeks of the procedure. On occasion, men may experience high fever, chills and sweats within a few hours or days after the biopsy. These severe infections require admission to the hospital and treatment with intravenous antibiotics. It is estimated that up to 1.4% of men will experience significant infection after biopsy, even if antibiotics are administered prior to the biopsy. At the Smilow Center, antibiotics are started the day before the procedure and continued for two days after the procedure. A second antibiotic is administered on the day of the biopsy. With this approach, infection rarely occurs.

Occasionally, men may experience a vasovagal episode during or immediately after the biopsy. This results in low blood pressure, slowed heart rate, sweating and nausea. It is typically due to rectal stimulation and usually resolves within a few minutes. If severe, fainting may occur. Men are advised to lie flat for a few minutes after the procedure and avoid physical exertion for 24 hours.

Most men may return to work the same day of the biopsy procedure, but they should avoid physical exertion for the remainder of the day.

Overall, complications of prostate biopsies are uncommon, but if they do occur, early recognition by the physician allows them to be managed relatively easily.

If bleeding is a potential complication of prostate biopsy, must I discontinue blood thinners?

In general, it is advisable to stop blood thinners a week before the procedure, although in some cases, the risk of coming off blood thinners exceeds the risk of bleeding from the biopsy. In these cases, the biopsy is conducted while the patient is maintained on blood thinners. In some men for whom it is too risky to discontinue blood thinners, a second, short-acting blood thinner may be started to keep the blood thin until the time of the procedure (bridging therapy). Prior to stopping blood thinners (aspirin, clopidogrel (Plavix) or warfarin (Coumadin), you should seek the approval of your cardiologist or primary care physician, who will help monitor your condition.

Does color Doppler ultrasound improve prostate cancer detection?

Color Doppler ultrasound is a method of ultrasound that allows assessment of blood flow superimposed over the conventional ultrasound image. Because areas of cancer may have increased blood flow, some physicians have suggested that color Doppler may improve the ability to detect cancer.

Careful studies suggest that color Doppler does not specifically detect cancer, since areas of increased blood flow may also represent inflammation, infection or even benign tissue. Therefore, at the Smilow Center, we use color Doppler to direct biopsies, but it never supersedes the need for a biopsy. In addition to color Doppler, Smilow Center physicians are also evaluating a number of investigative imaging modalities to enhance the detection of prostate cancer and potentially reduce the need for biopsy.

If the biopsy is negative, does this mean I don’t have prostate cancer?

A small fraction of men with a negative biopsy may still harbor a clinically significant prostate cancer because of sampling error. Small cancers, in particular, may be missed on a standard biopsy. The number of cores influences the likelihood of missing a prostate cancer; a 12-core biopsy is less likely to miss a cancer than a six-core biopsy.

Traditionally, transrectal ultrasound guided biopsy involved taking six cores from the base, midzone, and apex of the right and left prostate. In addition to having a low yield of detection, a big problem with six-core biopsies was that they did not adequately rule out cancer. Despite a negative six-core biopsy, a man had a 20%–25% likelihood of a missed cancer.

In 1998, a Smilow Center physician was the first to describe the routine use of 12 cores rather than six. (Levine MA, Ittman M, Melamed J, Lepor H. J. Urol. Feb; 159(2):471-5 (1998)). This allowed for the detection of more prostate cancers, with fewer false negatives. The use of 10 to 12 cores has now become a national standard of care to provide an adequate false negative rate and reduce the need for repetitive negative biopsies.

We routinely do not initially perform more than a 12-core biopsy, since this would increase the detection of clinically insignificant cancers (cancers that are not likely to cause harm). As such, the goal of prostate biopsy is not to rule out prostate cancer altogether, but instead to rule out cancers that have the potential to be harmful. With a negative 12-core biopsy, it is very likely that the patient does not have a potentially aggressive or harmful cancer unless the PSA continues to rise or if pre-malignant changes or atypical glands are noted in the first biopsy.

What are the advantages of the TargetScanTM biopsy system?

The TargetScanTM biopsy system is a computerized template biopsy system. The ultrasound probe is placed in the rectum, aligned with the prostate and then fixed to a rigid stand. The probe does not move once placed in this position. The computer moves a device inside the probe to acquire images of the prostate every 5 mm and then makes recommendations on the placement of the biopsy needle based on a three-dimensional reconstruction of the prostate. The theoretical advantages of TargetScanTM include more accurate needle placement and recording of the precise locations of any abnormalities. Smilow Center physicians have led the way in clinical development of the TargetScanTM system (Taneja SS. Rev. Urol. 8:173-182 (2006)).

A Smilow Center physician recently led a national study evaluating the effectiveness of the TargetScanTM computerized template biopsy (Megwalu II, Ferguson GG, Wei JT, Mouraviev V, Polascik TJ, Taneja S, Black L, Andriole GL, Kibel AS. BJU Int. 2008; 102(5):546-50). This initial study suggested that TargetScanTM can detect prostate cancers at a rate similar to conventional biopsy, but with improved mapping of disease and possibly improved estimation of disease volume.

What is a saturation biopsy?

A saturation biopsy is a technique in which multiple biopsies are dispersed in a systematic manner throughout the entire prostate gland, thereby ‘saturating’ the gland with sampling.

Saturation biopsy is typically used for two purposes:

(i) To detect cancers in men who continue to have a rising PSA or a markedly elevated PSA after negative traditional biopsies

(ii) To better map the location and extent of prostate cancer in men with low-risk disease who are considering active surveillance or focal therapy

Saturation biopsy may be conducted by a transrectal approach or through a transperineal approach. The transperineal technique is typically conducted under general anesthesia. Biopsy needles are inserted through the skin in the area between the scrotum and the anus. Typically, 60–100 cores are taken at a spacing of 5–10 mm. In the transrectal saturation technique, 20–36 cores are typically taken, depending on the physician’s preferred technique. At the Smilow Center, we use the transrectal approach more frequently.

My PSA is going up despite a negative biopsy. Do I need a second biopsy?

A rising PSA after a negative biopsy is a concern because of the possibility that a cancer was missed on the first biopsy. Nonetheless, several factors must be considered before proceeding with a biopsy. First, the biopsy itself may produce prostatic inflammation that increases the PSA over the pre-biopsy level for several months after the biopsy. This effect may be more pronounced if a patient experiences infection after the biopsy.

There can be tremendous variability between PSA measurements, owing to individual physiology, laboratory variability, recent manipulation of the prostate, infection or even ejaculation. At the Smilow Center, an observation of rising PSA is made on the basis of several PSA measurements, rather than just one, in order to overcome variability. A Smilow physician has recently demonstrated that overcoming the variability of PSA greatly improves the prediction of a missed cancer in follow-up (Kumar A, Godoy G, Taneja SS. CJU 2009; 16(3):4655-9).

If the PSA is rising, a repeat biopsy is warranted. It is important that the repeat biopsy sample alternate sites within the prostate. Studies have shown that most cancers identified on repeat biopsy are located in either the far lateral or anterior regions of the prostate. Therefore, repeat biopsies typically sample those areas not routinely sampled on first biopsy. At the Smilow Center, we do not use a saturation technique on all men requiring a repeat biopsy, but we do sample the transition zone around the urethral tube in the anterior prostate.

How many consecutively rising PSA measurements would trigger a second biopsy?

Because of the difficulty with PSA variability, one cannot determine if a PSA is truly rising on the basis of one or two measurements. At the Smilow Center, we recognize that a number of factors, including measurement variability, testosterone level, infection, inflammation and even ejaculation may result in a rise in the PSA. Therefore, a rise in more than one measurement is necessary to warrant a repeat biopsy. A concerning rate of increase is typically more than 0.5 ng/dl per year when averaged over a minimum of three measurements, including the pre-biopsy measurement.

Are different techniques used in the first and second biopsies?

Studies have shown that most cancers identified on repeat biopsy are located in the far lateral or anterior regions of the prostate. Therefore, repeat biopsy strategies typically sample those areas not routinely sampled on first biopsy. Many urologists routinely perform saturation biopsies of the prostate on repeat biopsy. This technique calls for sampling of the prostate every 5 mm throughout the gland, requiring the use of general anesthesia. At the Smilow Center, we do not employ a saturation technique on all men in need of repeat biopsy, but we do sample the transition zone, an area located around the urethral tube in the anterior prostate. In doing so, we typically take a minimum of 18–20 cores through a transrectal approach.

What is HGPIN?

High-grade prostatic intraepithelial neoplasia (HGPIN) is believed to be a precancerous finding within the prostate. HGPIN is not prostate cancer. Most men with prostate cancer have areas of HGPIN elsewhere in the prostate, suggesting that, in many cases, prostate cancer development progresses through HGPIN to invasive cancer. Recent research has suggested that men with HGPIN are more likely to have a simultaneous prostate cancer than men without HGPIN and are more likely to be diagnosed with prostate cancer later in life.

Studies of men with HGPIN diagnosed through a six-core biopsy have suggested that the risk of prostate cancer on an immediate repeat biopsy is about 50%. Immediate repeat biopsy is generally recommended for men with isolated HGPIN after a six-core biopsy. Physicians at the Smilow Center were the first to demonstrate that men diagnosed with HGPIN through a 12-core biopsy are rarely found to have prostate cancer on immediate repeat biopsy, suggesting that a 12-core biopsy is generally adequate in ruling out a significant coexistent cancer (Lefkowitz G, Sidhu G, Torre P, Lepor H, Taneja SS. Urol. 58(6): 999-1003 (2001)). In addition, research by Smilow Center physicians has shown that, among men diagnosed with HGPIN on a 12-core sampling, 25% were found to have cancer in a repeat biopsy 3 years after the first biopsy (Lefkowitz GK, Taneja SS, Brown J, Melamed J, Lepor H. J. Urol. 168:1415-18 (2002)). The likelihood of cancer on the follow-up biopsy was not predicted by changes in PSA level. On the basis of these studies, the Smilow Center recommends routine follow-up or surveillance biopsies every 2–3 years in all men with HGPIN found on routine 12-core biopsy. Using this approach, we have continued to demonstrate an approximate 25% rate of cancer detection at every 3-year interval of follow-up (Godoy G, Taneja SS. Prostate Cancer Prostatic Dis. 11(1):20-31 (2008)).

Because men with HGPIN are thought to be at a higher risk of cancer detection in follow-up, they may be ideal candidates for chemoprevention strategies. A Smilow Center physician is currently the lead investigator of a national clinical study evaluating the effectiveness of toremifene (a selective estrogen receptor modulator or blocking agent) in prevention of prostate cancer in men with HGPIN (Taneja SS. Rev. Urol. 7:S19-S29 (2005); Taneja SS et al. Expert Opin. Investig. Drugs 15(3):293-305 (2006)). The study includes 1,590 men across North and South America and is scheduled for completion in early 2010. Additional preventive studies for men with HGPIN are planned.

The Smilow Center recommends that men with HGPIN should consider taking a 5-ARI with the intent of decreasing the risk of developing detectible prostate cancer. We also recommend consultation with one of our expert naturopathic physicians to discuss how diet, lifestyle management and various supplements may impact the development of prostate cancer.

What is ASAP or atypia on a biopsy?

Atypical small acinar proliferation (ASAP) indicates prostate glands that are suspicious for cancer in their appearance but inadequate in number to allow a firm diagnosis of prostate cancer.

When viewed under a microscope, normal prostate glands appear as large floppy circles, whereas cancerous glands appear as clusters of small, tightly packed circles with a single layer of cells. When only a few small, circular glands are observed, it is difficult to determine if this represents the edge of a cluster of cancer or the edge of a larger, normal gland. In this setting, the pathologist who examines the sample may be unable to make a firm diagnosis. Because this often reflects the uncertainty of the pathologist, less-experienced pathologists will diagnose ASAP on biopsy more often than experienced pathologists. If your biopsy shows ASAP, a second opinion by an experienced pathologist is usually a good idea before any action is taken. If an experienced pathologist confirms the presence of ASAP, a repeat biopsy with saturation sampling of the affected area should be carried out immediately to rule out cancer.