PROSTATE CANCER: DIAGNOSIS AND TREATMENT

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1 PROSTATE CANCER: DIAGNOSIS AND TREATMENT Jassin M. Jouria, MD Dr. Jassin M. Jouria is a medical doctor, professor of academic medicine, and medical author. He graduated from Ross University School of Medicine and has completed his clinical clerkship training in various teaching hospitals throughout New York, including King s County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep tutor and instructor for Kaplan. He has developed several medical courses and curricula for a variety of educational institutions. Dr. Jouria has also served on multiple levels in the academic field including faculty member and Department Chair. Dr. Jouria continues to serves as a Subject Matter Expert for several continuing education organizations covering multiple basic medical sciences. He has also developed several continuing medical education courses covering various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital s Department of Surgery to develop an e-module training series for trauma patient management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy & Physiology. ABSTRACT The diagnosis and treatment of prostate cancer has undergone much progress in terms of new preventive and medical therapies in addition to surgical approaches based on prostate cancer type and staging. While some lifestyle patterns have been studied to prevent prostate cancer, more research is needed to determine how lifestyle factors are associated with a reduction in the incidence of prostate cancer. Challenges and complications in the diagnosis and treatment of prostate cancer that health providers and nurses face while caring for patients are discussed. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1

2 Continuing Nursing Education Course Director & Planners William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster, Susan DePasquale, MSN, FPMHNP-BC, Lead Nurse Planner Policy Statement This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities. Continuing Education Credit Designation This educational activity is credited for 5 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity. Pharmacology content is 1 hour. Statement of Learning Need Prostate cancer is one of the most prevalent forms of cancer among men, second only to skin cancer. Health professionals need to be knowledgeable about the symptoms, stages, and various treatments to ensure the best possible outcome of care for patients with prostate cancer. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 2

3 Course Purpose To provide nurses and associates with knowledge of prevention, cause and treatment of prostate cancer. Target Audience Advanced Practice Registered Nurses and Registered Nurses (Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion) Course Author & Director Disclosures Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA Susan DePasquale, MSN, FPMHNP-BC all have no disclosures Acknowledgement of Commercial Support There is no commercial support for this course. Activity Review Information Reviewed by Susan DePasquale, MSN, FPMHNP-BC Start Date: 4/26/2016 Termination Date: 4/26/2019 Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article. Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3

4 1. Prostate cancer typically develops in the zone of the prostate. a. transition b. central c. anterior d. peripheral 2. The is primarily comprised of muscle tissue. a. anterior zone b. vas deferens c. central zone d. seminal vesicles 3. Lack of vegetables in the diet (especially broccoli-family vegetables) is linked to a. slow-growing tumors. b. low-risk prostate cancer. c. higher risk of aggressive prostate cancer. d. genetic factors related to prostate cancer. 4. True or False: Body mass index, a measure of obesity, IS linked to being diagnosed with prostate cancer. a. True b. False 5. In most instances, when physicians discuss prostate cancer, they re referring to a. urothelial cell carcinoma. b. bladder cancer. c. sarcoma. d. adenocarcinoma. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 4

5 Introduction Prostate cancer is one of the most prevalent forms of cancer among men, second only to skin cancer. It has a very high success rate in treatment and recovery due in part to its typical slow-growth pattern. However, it is important to remember that not all forms of prostate cancer are slow growing and that not all prostate cancer patients are cured. As a result, health professionals need to be aware of the symptoms, stages, and various treatments to ensure the best possible outcome for their patients. This course will provide a general overview of current concepts, diagnostic advances, and novel therapeutic approaches to the management of prostate cancer. The Prostate The prostate is a conglomeration of tiny glands, ducts, and muscle tissue encased by fibrous tissue. It produces fluid that contains hormones and proteins to keep sperm alive after ejaculation as the sperm searches for an egg to fertilize. The average size of a prostate is about 30 to 40 grams, about the size of a small lime or walnut. Its texture is firm. About one-third of the prostate is composed of muscular tissue, with the rest being glandular tissue. As a man ages, his prostate often gets bigger, sometimes doubling or tripling in size. Although there is a lot of discussion about prostate enlargement in aging men and the uncomfortable symptoms that this can cause, it is important to remember that not all men experience prostate enlargement, and cancer is not responsible for this enlargement. The prostate s zones include the transition, the central, the anterior, and the peripheral. 1 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 5

6 Transition Zone: The transition zone is the most interior part of the prostate; it immediately surrounds the urethra (the slender tube that carries urine away from the bladder and out of the body through the tip of the penis). The transition zone can begin to grow after age 40, with this noncancerous enlargement possibly leading to urinary difficulties. Central Zone: The central zone is located near the bladder and is the seat of about one third of the glands that make and secrete prostatic fluid. The central zone, similar to the transition zone, is generally the part of the prostate that grows after a man turns age 40. Prostate cancer is unusual in the central zone and if it does develop, it tends to be a slower growing type of cancer. Anterior Zone: The anterior zone is primarily comprised of muscle tissue. Peripheral Zone: The peripheral zone is located at the back of the gland and is the portion closest to the rectum. It contains most of the secretionproducing glands and is where prostate cancer typically develops. Medical providers typically describe a right side and a left side when referring to the prostate, but in reality there is only a subtle demarcation between the two sides. Think of a plum. It is one fruit but the small groove down the middle leaves the impression of two halves. That s similar to the prostate gland. 2 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 6

7 A measurement of the location of the prostate within the pelvic area will show that it is approximately two inches from the perineum, which is the region of exterior skin and internal muscle between the anus and the scrotum. The gland sits just below the bladder and in front of the rectum. Off the base of the prostate and behind the bladder are the two seminal vesicles, which produce most of the fluid that makes up the ejaculate. The base of the prostate is the wider part of the gland that nestles up to the bladder. The apex is the more pointed end of the gland that faces down toward the perineum. Just before ejaculation, sperm from the testicles is transported into the urethra by a long tube called the vas deferens. This sperm combines with fluid both from the seminal vesicles and the prostate, creating semen. The prostate and adjacent muscular contractions then propel the semen out of the urethra through the tip of the penis for ejaculation. 3 Prostate Cancer Incidence And Statistics The diagnosis of prostate cancer rapidly increased in the mid-1980s, with the advent of the serological biomarker prostate specific antigen (PSA) test (discussed below), which has played a pivotal role in the screening and early detection of prostate cancer worldwide. The current lifetime risk of developing prostate cancer is 17%, with an estimated lifetime cancer specific mortality risk of 3%. Prostate cancer is the most commonly diagnosed non skin cancer in men in the U.S., with a lifetime risk for diagnosis currently estimated at 15.9%. Most cases of prostate cancer have a good prognosis even without treatment, but some cases are aggressive; the lifetime risk for dying of prostate cancer is 2.8%. Over two million men in the U.S. count themselves as prostate cancer survivors, and this number continues to grow. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7

8 Risk Factors Of Prostate Cancer There are several major factors that influence risk, and some of them unfortunately cannot be changed. 4 Age: Prostate cancer is rare before age 50 years, and very few men die of prostate cancer before age 60 years. Seventy percent of deaths due to prostate cancer occur after age 75 years. Thus, the older the patient, the more likely he is to be diagnosed with prostate cancer. For example, only 1 in 10,000 men under age 40 will be diagnosed with prostate cancer; the rate shoots up to 1 in 38 for ages 40 to 59; and 1 in 14 for ages 60 to 69. In fact, more than 65% of all prostate cancers are diagnosed in men over the age of 65. The average age at diagnosis of prostate cancer in the U.S. is 69 years. After that age, the chance of developing prostate cancer becomes more common than any other cancer in men or women. Race: African American men are more likely to develop prostate cancer compared with Caucasian men and are nearly 2.5 times as likely to die from the disease. Conversely, Asian men who live in Asia have the lowest risk. Family history/genetics: A man with a father or brother who developed prostate cancer is twice as likely to develop the disease. This risk is further increased if the cancer was diagnosed in family members at a younger age (less than 55 years of age) or if it affected three or more family members. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 8

9 Location of residence: For men in the U.S., the risk of developing prostate cancer is 17%. For men who live in rural China, it s 2%. However, when Chinese men move to the western culture, their risk increases substantially. Men who live in cities north of 40 degrees latitude (north of Philadelphia, Pennsylvania, Columbus, Ohio, and Provo, Utah, for instance) have the highest risk for dying from prostate cancer of any men in the U.S. This effect appears to be mediated by inadequate sunlight during three months of the year, which reduces vitamin D levels. Aggressive versus Slow-Growing Cancers In the past few years, health providers have realized that prostate cancer is actually linked to several diseases with different causes. More aggressive and fatal cancers likely have different underlying causes than slow-growing tumors. For example, while smoking has not been thought to be a risk factor for low-risk prostate cancer, it may be a risk factor for aggressive prostate cancer. Likewise, lack of vegetables in the diet (especially broccoli-family vegetables) is linked to a higher risk of aggressive prostate cancer, but not to low-risk prostate cancer. 5 Body mass index, a measure of obesity, is not linked to being diagnosed with prostate cancer overall. In fact, obese men may have relatively lower PSA levels than non-obese men due to dilution of the PSA in a larger blood volume. However, obese men are more likely to have aggressive disease. 6 Other risk factors for aggressive prostate cancer include: Tall height Lack of exercise and a sedentary lifestyle High calcium intake African-American race nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 9

10 Family history Agent Orange exposure Research in the past few years has shown that diet modification may decrease the chances of developing prostate cancer, reduce the likelihood of having a prostate cancer recurrence, or help slow the progression of the disease. Prostate Conditions and Other Related Risks The most common misconception is that the presence of non-cancerous conditions of the prostate will increase the risk of prostate cancer. While these conditions can cause symptoms similar to those of prostate cancer and should be evaluated by a physician, there is no evidence to suggest that having the following conditions will increase a man s risk for developing prostate cancer. 7 Benign Prostatic Hyperplasia and Prostatitis Benign Prostatic Hyperplasia (BPH) is a non-cancerous enlargement of the prostate. Because the urethra (the tube that carries urine from the bladder out of the body) runs directly through the prostate, enlargement of the prostate in BPH squeezes the urethra, making it difficult and often painful for men to urinate. Prostatitis, an infection in the prostate, is the most common cause of urinary tract infections in men. Most treatment strategies are designed to relieve the symptoms of prostatitis, which include fever, chills, burning during urination, or difficulty urinating. There have been links between inflammation of the prostate and prostate cancer in several studies. This may be a result of nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 10

11 being screened for cancer just by having prostate related symptoms, and currently this is an area of controversy. Sexual Activity High levels of sexual activity or frequent ejaculation have been rumored to increase prostate cancer risk. This is untrue. In fact, studies show that men who report more frequent ejaculations may have a lower risk of developing prostate cancer. Vasectomy Having a vasectomy was originally thought to increase a man s risk, but this has since been disproven. Medications Several recent studies have shown a link between aspirin intake and a reduced risk of prostate cancer by 10-15%. This may result from different screening practices, through a reduction of inflammation, or other unknown factors. The class of drugs called the statins - known to lower cholesterol - has also recently been linked to a reduced risk of aggressive prostate cancer in some studies. Alcohol There is no link between alcohol and prostate cancer risk. Vitamin E Recent studies have not shown a benefit to the consumption of vitamin E or selenium (in the formulations studied) in the prevention of prostate cancer. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 11

12 Overview of Prostate Cancer Prostate cancer is an uncontrolled growth of cells that line the ducts of the prostate gland. These abnormal cells can spread throughout the prostate and nearby organs, such as the seminal vesicles. If not caught early, they can spread (metastasize) to other regions of the body through the lymph or blood systems. 8 In most instances, when health providers discuss prostate cancer, they are referring to adenocarcinoma. This cancer arises from the cells of the prostate s ducts. However, there are a few other rare cancers in the prostate. One is urothelial cell carcinoma (UCC). Urothelial cell carcinoma originates from the layer of cells that line the inside of the urethra and the bladder. This tumor is frequently seen in association with bladder cancer. 9 An extremely rare cancer of the prostate is a sarcoma. A sarcoma originates from the muscular and connective tissue in the prostate and is treated quite differently. Compared to most other kinds of cancer, prostate adenocarcinoma is usually very slow growing. It can begin at a relatively early age, possibly when a man is in his 30s or 40s. Because it grows so slowly, it is not usually diagnosed until after age 55 to 60. In some situations, though, the cancer will grow and spread very fast. There are several ways to predict the tumor s speed of growth. The first is to watch how fast the PSA level is rising; this is called PSA velocity. Another measure is the Gleason score. A higher Gleason score indicates a more aggressive cancer. A final method involves repeated physical examination or radiology studies (such as an MRI or bone scans) to monitor growth of the cancer. 10,11 Prostate cancer can spread in several ways. It usually spreads first through the capsule of the prostate. This spread outside the gland is often only a few nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 12

13 millimeters. It can also move into the seminal vesicles. Spread to the seminal vesicles is seen less often these days, probably because the disease is being caught earlier. 12 Prostate cancer can occasionally spread to other parts of the body. Cancer cells can enter the lymphatic vessels around the prostate and then spread to the lymph nodes in the pelvis. Another way prostate cancer spreads is through the bloodstream. Ultimately, cancer cells that enter the lymph channels can spread (through the blood) to almost any organ in the body. Because of what seem to be special growth factors, the prostate cancer cells have an affinity for growing in bone often the bones of the spine, pelvis, or long bones, such as the femur (upper leg) or humerus (upper arm). 13 To determine if prostate cancer has spread to the bone, a bone scan is performed in some prostate cancer patients. If prostate cancer cells begin to grow in the bones, it is still considered prostate cancer (not bone cancer) and may be treated with hormonal and radiation therapies. 14 Symptoms of Prostate Cancer Many times, prostate cancer will produce no recognizable symptoms in patients. However, many men will not recognize when they are experiencing symptoms because they are similar to many other conditions. For individuals who do notice the presence of symptoms, the following are the most common that they experience. 27 Local Symptoms: Urinary frequency Urinary urgency Decreased stream Hematuria nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13

14 Metastatic Symptoms: Weight loss Loss of appetite Bone pain Lower extremity pain Edema Uremic symptoms Diagnosing Prostate Cancer Typically, screening will be conducted in order of least to most invasive. However, if there is significant concern that the cancer may already have reached an advanced stage, more aggressive screening procedures may be used without conducting initial diagnostic procedures. The provider will determine which screening procedures to order depending in each individual patient s needs and situation. 28 All contemporary recommendations for prostate cancer screening incorporate the measurement of serum PSA levels; other methods of detection, such as digital rectal examination or ultrasonography, may be included. Prostate cancer screening will find prostate cancer in one in every eight men during their lifetime. Prostate cancer represents 25% of all new cases of male cancers. Screening is designed to detect early stage, asymptomatic prostate cancer, as the patient's chances of cure are higher when the cancer is diagnosed at an early stage. 15 Before specific screening procedures are discussed, it is important to be aware of the concern that prostate cancer may be over-diagnosed and over-treated. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 14

15 Over-diagnosis and Over-treatment Although the PSA test lowers mortality rates for prostate cancer, there is still concern that over-diagnosis may lead to over-treatment of cancers that would not progress enough to significantly affect a patient s health for several years: 16 for example, there is convincing evidence that PSA-based screening programs result in the detection of many cases of asymptomatic prostate cancer. A substantial percentage of men who have asymptomatic cancer detected by PSA screening have a tumor that either will not progress or will progress so slowly that it would have remained asymptomatic for the man's lifetime. The terms over-diagnosis or pseudo-disease are used to describe both situations. The rate of over-diagnosis of prostate cancer increases as the number of men subjected to biopsy increases. The number of cancer cases that could be detected in a screened population is large. A single study in which men eligible for PSA screening had a biopsy regardless of PSA level detected cancer in nearly 25% of men. The rate of over-diagnosis also depends on life expectancy at the time of diagnosis. A cancer diagnosis in men with shorter life expectancies because of chronic diseases or age is much more likely to lead to over-diagnosis. The precise magnitude of over diagnosis associated with any screening and treatment program is difficult to determine, but estimates from the 2 largest trials suggest over-diagnosis rates of 17% to 50% for prostate cancer screening. 9,16-19 Benefits of Detection and Early Treatment The primary goal of prostate cancer screening is to reduce deaths due to prostate cancer and, thus, increase length of life. An additional important outcome would be a reduction in the development of symptomatic metastatic disease. Reduction in prostate cancer mortality was the primary nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 15

16 outcome used in available randomized, controlled trials of prostate cancer screening. Although one screening trial reported on the presence of metastatic disease at the time of prostate cancer diagnosis, no study reported on the effect of screening on the development of subsequent metastatic disease, making it difficult to assess the effect of lead-time bias on the reported rates. 20 Men with screen-detected cancer can potentially fall into 1 of 3 categories: those whose cancer will result in death despite early diagnosis and treatment, those who will have good outcomes in the absence of screening, and those for whom early diagnosis and treatment improve survival. Only randomized trials of screening allow an accurate estimate of the number of men who fall into the last category. There is convincing evidence that the number of men who avoid dying from prostate cancer because of screening after 10 to 14 years is, at best, very small. The U.S. Preventive Services Task Force (USPSTF) considered two major trials of PSA screening, which were the U.S. PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial and the ERSPC (European Randomized Study of Screening for Prostate Cancer). The U.S. trial did not demonstrate any reduction of prostate cancer mortality. The European trial found a reduction in prostate cancer deaths of approximately 1 death per 1000 men screened in a subgroup aged 55 to 69 years. This result was heavily influenced by the results of 2 countries; 5 of the 7 countries reporting results did not find a statistically significant reduction. All-cause mortality in the European trial was nearly identical in the screened and nonscreened groups. There is adequate evidence that the benefit of PSA screening and early treatment ranges from 0 to 1 prostate cancer deaths avoided per 1000 men screened. 13,21-25 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 16

17 Harms Related to Screening and Diagnostic Procedures Convincing evidence demonstrates that the PSA test often produces falsepositive results: approximately 80% of positive PSA test results are falsepositive when cutoffs between 2.5 and 4.0 µg/l are used (4.0 ng/ml is the total PSA value below which prostate cancer is considered unlikely). There is adequate evidence that false-positive PSA test results are associated with negative psychological effects, including persistent worry about prostate cancer. Men who have a false-positive test result are more likely to have additional testing, including 1 or more biopsies, in the following year than those who have a negative test result. Over 10 years, approximately 15% to 20% of men will have a PSA test result that triggers a biopsy, depending on the PSA threshold and testing interval used. New evidence from a randomized trial of treatment of screendetected cancer indicates that roughly one third of men who have prostate biopsy experience pain, fever, bleeding, infection, transient urinary difficulties, or other issues requiring clinician follow-up that the men consider a moderate or major problem ; approximately 1% require hospitalization. 16,17,26 Screening For Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. 15 The USPSTF considered the magnitude of these harms associated with screening and diagnostic procedures to be at least small. Although the precise, long-term effect of PSA screening on prostate cancer specific mortality remains uncertain, existing studies adequately demonstrate that the reduction in prostate cancer mortality after 10 to 14 years is, at most, very small, even for men in what seems to be the optimal age range of 55 to 69 years. There is no apparent reduction in all-cause mortality. In contrast, the harms associated with the diagnosis and treatment of screen-detected cancer are common, occur early, often persist, and include a small but real risk for premature death. Many more men in a screened population will experience the harms of screening and treatment of screen-detected disease than will experience the benefit. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 17

18 The inevitability of overdiagnosis and overtreatment of prostate cancer as a result of screening means that many men will experience the adverse effects of diagnosis and treatment of a disease that would have remained asymptomatic throughout their lives. Assessing the balance of benefits and harms requires weighing a moderate to high probability of early and persistent harm from treatment against the very low probability of preventing a death from prostate cancer in the long term. The USPSTF concludes that there is moderate certainty that the benefits of PSA-based screening for prostate cancer do not outweigh the harms. Implementation Although the USPSTF discourages the use of screening tests for which the benefits do not outweigh the harms in the target population, it recognizes the common use of PSA screening in practice today and understands that some men will continue to request screening and some physicians will continue to offer it. The decision to initiate or continue PSA screening should reflect an explicit understanding of the possible benefits and harms and respect the patients' preferences. Physicians should not offer or order PSA screening unless they are prepared to engage in shared decision-making that enables an informed choice by the patients. Similarly, patients requesting PSA screening should be provided with the opportunity to make informed choices to be screened that reflect their values about specific benefits and harms. Community- and employer-based screening should be discontinued. The treatment of some cases of clinically localized prostate cancer can change the natural history of the disease and may reduce morbidity and mortality in a small percentage of men, although the prognosis for clinically localized cancer is generally good regardless of the method of detection, even in the absence of treatment. The primary goal of PSA-based screening is to find men for whom treatment would reduce morbidity and mortality. Studies demonstrate that the number of men who experience this benefit is, at most, very small, and PSA-based screening as currently implemented in the United States produces more harms than benefits in the screened population. It is not known whether an alternative approach to screening and management of screen-detected disease could achieve the same or greater benefits while reducing the harms. Focusing screening on men at increased risk for prostate cancer mortality may improve the balance of benefits and harms, but existing studies do not allow conclusions about a greater absolute or relative benefit from screening in these populations. Lengthening the interval between screening tests may reduce harms without affecting cancer mortality; the only screening trial that demonstrated a prostate cancer specific mortality benefit generally used a 2- to 4-year screening interval. Other potential ways to reduce diagnostic- and treatment-related harms include increasing the PSA threshold used to trigger the decision for biopsy or need for treatment, or reducing the number of men having active treatment at the time of diagnosis through watchful waiting or active surveillance. Periodic digital rectal examinations could also be an alternative strategy worthy of further study. In the only randomized trial demonstrating a mortality reduction from radical prostatectomy for clinically localized cancer, a high percentage of men had palpable cancer. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 18

19 All of these approaches require additional research to better elucidate their merits and pitfalls and more clearly define an approach to the diagnosis and management of prostate cancer that optimizes the benefits while minimizing the harms. Patient Population Under Consideration This recommendation applies to men in the general U.S. population. Older age is the strongest risk factor for the development of prostate cancer. However, neither screening nor treatment trials show benefit in men older than 70 years. Across age ranges, black men and men with a family history of prostate cancer have an increased risk of developing and dying of prostate cancer. Black men are approximately twice as likely to die of prostate cancer than other men in the United States and the reason for this disparity is unknown. Black men represented a small minority of participants in the randomized clinical trials of screening (4% of enrolled men in the PLCO trial were non-hispanic black; although the ERSPC and other trials did not report the specific racial demographic characteristics of participants, they probably were predominately white). Thus, no firm conclusions can be made about the balance of benefits and harms of PSA-based screening in this population. However, it is problematic to selectively recommend PSA-based screening for black men in the absence of data that support a more favorable balance of risks and benefits. A higher incidence of cancer will result in more diagnoses and treatments, but the increase may not be accompanied by a larger absolute reduction in mortality. Preliminary results from PIVOT (Prostate Cancer Intervention Versus Observation Trial), in which 30% of enrollees were black, have become available since the publication of the USPSTF's commissioned evidence reviews. Investigators found no difference in outcomes due to treatment of prostate cancer in black men compared with white men. Exposure to Agent Orange (a defoliant used in the Vietnam War) is considered to be a risk factor for prostate cancer, although few data exist on the outcomes or effect of PSA testing and treatment in these persons. The Veterans Health Administration considers prostate cancer in Vietnam veterans who were exposed to Agent Orange a serviceconnected condition. The USPSTF did not evaluate the use of the PSA test as part of a diagnostic strategy in men with symptoms potentially suggestive of prostate cancer. However, the presence of urinary symptoms was not an inclusion or exclusion criterion in screening or treatment trials, and approximately one quarter of men in screening trials had bothersome lower urinary tract symptoms (nocturia, urgency, frequency, and poor stream). The presence of benign prostatic hyperplasia is not an established risk factor for prostate cancer, and the risk for prostate cancer among men with elevated PSA levels is lower in men with urinary symptoms than in men without symptoms. This recommendation also does not include the use of the PSA test for surveillance after diagnosis or treatment of prostate cancer and does not consider PSA-based testing in men with known BRCA gene mutations who may be at increased risk for prostate cancer. Screening Tests Prostate-specific antigen based screening in men aged 50 to 74 years has been evaluated in 5 unique randomized, controlled trials of single or interval PSA testing with various PSA cutoffs and screening intervals, along with other screening methods, such as digital rectal examination or transrectal ultrasonography. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 19

20 Screening tests or programs that do not incorporate PSA testing, including digital rectal examination alone, have not been adequately evaluated in controlled studies. The PLCO trial found a nonstatistically significant increase in prostate cancer mortality in the annual screening group at 11.5 and 13 years, with results consistently favoring the usual care group. A prespecified subgroup analysis of men aged 55 to 69 years in the ERSPC trial demonstrated a prostate cancer mortality rate ratio (RR) of 0.80 (95% CI, 0.65 to 0.98) in screened men after a median follow-up of 9 years, with similar findings at 11 years (RR, 0.79 [CI, 0.68 to 0.91]). Of the 7 centers included in the ERSPC analysis, only 2 countries (Sweden and the Netherlands) reported statistically significant reductions in prostate cancer mortality after 11 years (5 did not), and these results seem to drive the overall benefit found in this trial. No study reported any factors, including patient age, adherence to site or study protocol, length of follow-up, PSA thresholds, or intervals between tests, that could clearly explain why mortality reductions were larger in Sweden or the Netherlands than in other European countries or the United States (PLCO trial). Combining the results through meta-analysis may be inappropriate due to clinical and methodological differences across trials. No study found a difference in overall or all-cause mortality. This probably reflects the high rates of competing mortality in this age group, because these men are more likely to die of prostate cancer, as well as the limited power of prostate cancer screening trials to detect differences in all-cause mortality, should they exist. Even in the core age group of 55 to 69 years in the ERSPC trial, only 462 of deaths were due to prostate cancer. The all-cause mortality RR was 1.00 (CI, 0.98 to 1.02) in all men randomly assigned to screening versus no screening. Results were similar in men aged 55 to 69 years. The absence of any trend toward a reduction in all-cause mortality is particularly important in the context of the difficulty of attributing death to a specific cause in this age group. Diagnostic Procedures To Determine Prostate Cancer There are a number of diagnostic procedures that can be used to determine the presence of prostate cancer. Digital Rectal Exam During a digital rectal exam (DRE), the health provider inserts a gloved finger inside the rectum to examine the part of the prostate that s closest to the rectal wall. The provider is searching for any areas that feel abnormal, or have an unusual firmness or a lump (nodule). Such an abnormality may nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20

21 indicate the presence of prostate cancer. Simply because the health provider feels an irregularity doesn t mean it s prostate cancer. 29 In most prostate cancer cases diagnosed today, the DRE does not reveal a nodule the doctor can feel (palpate). This is either because the cancer is small and well hidden within the normal tissue or it s located in a portion of the gland that s inaccessible from the rectal area. It s the PSA blood test that usually finds these early, nonpalpable tumors. 30 Prostate Specific Antigen The use of the prostate-specific antigen (PSA) test for prostate cancer screening (since the 1990s) has led to increased early diagnoses. Prostate specific antigen is an enzyme produced by the prostate. Semen coagulates after ejaculation, and the PSA enzyme helps turn the congealed semen back into liquid so sperm can swim freely and fertilization may take place. It s normal for small amounts of PSA to leak into a man s bloodstream. The PSA blood test measures nanograms (one thousand-millionth of a gram) of PSA per milliliter of serum (the liquid part of blood), and it s written as ng/ml. 31 Noncancerous conditions, such as benign prostatic hyperplasia (BPH), prostate inflammation, prostate infection, or trauma, can elevate PSA because these conditions may cause more of the enzyme to seep into the bloodstream. An elevated PSA does not necessarily indicate cancer. It only points to something that needs further investigation. 32 Although a large number of men undergo annual screening, PSA testing has never been scientifically proven to reduce the risk of dying from prostate cancer. Because false positives can lead to unnecessary biopsies - and a nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 21

22 biopsy is an invasive procedure - not everyone in the medical establishment universally recommends this screening procedure. 33 The National Cancer Institute started the multi-institutional Prostate, Lung, Colorectal, Ovarian (PLCO) cancer screening trial in 1993 to explore whether screening for a number of cancers, including prostate, is valuable. Early findings of the PLCO trial suggest that if the PSA level is less than 1.0 ng/ml, then the patient could reduce testing to once every five years. If this PSA test is lower than 2.0 ng/ml, then the health provider might suggest getting the PSA re-tested every other year. And anyone with a PSA level above 2.0 ng/ml should continue to get a yearly PSA test. Although these are the standard recommendations, the provider will make screening recommendations based on the individual s personal medical history. 34 The PSA readings will vary depending on a number of factors. The following is a list of the different types of PSA readings one must consider when screening. Normal PSA Reading The upper limit of a normal PSA initially was thought to be 4.0 ng/ml. This level comes from screening studies that contained groups of men of various ages. The goal was to choose a PSA level that would be as sensitive as possible to cancer but not so low that many men with minimally increased PSA from benign causes would be unnecessarily biopsied. The most recent information has suggested that it may be reasonable to consider lowering the normal PSA level to 2.5 or 3.0 ng/ml, particularly for younger men. The reason for this is that while the likelihood of a positive biopsy in the ng/ml range is about 25 percent, the likelihood of a nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22

23 positive biopsy in the ng/ml range drops only a bit, to 15 percent to 20 percent. For some men, this one in five risk may be sufficiently high to consider a biopsy if the PSA falls in this range. Age Adjusted PSA Prostate specific antigen levels tend to increase as a man ages and his prostate volume increases. What may be a normal amount of PSA for a man at age 50 will be different by the time he reaches 70. For instance, if a man is younger than 50 and has a PSA of 4.5 ng/ml, his doctor might call for a biopsy. But if a 75-year-old s PSA is 4.5 ng/ml, his doctor might consider this normal for his age and not request additional tests. It is important to remember that age adjusted PSA levels are controversial and not everyone in the medical community agrees about their accuracy or usefulness. It has been suggested that while age adjusted PSA levels may pick up more cancers in the younger age group by using lower normal PSA levels, more cancer may be missed in older patients. Age Range Worrisome PSA Level >2.5 ng/ml >3.0 ng/ml >3.5 ng/ml 70 + >4.0 ng/ml Free PSA Most PSA binds to other proteins in the blood. Because this PSA is complexed or bonded to these proteins, it s often called complexed PSA. The remaining unattached PSA is termed free PSA. Because the type of nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 23

24 PSA varies with different kinds of prostate tissue, men with a lower percentage of free PSA have a higher risk for prostate cancer. For example, a man whose total PSA is 8.0 ng/ml with 8 percent free PSA has a greater chance of having prostate cancer than his next door neighbor whose total PSA also is 8.0 ng/ml but with 35 percent free PSA. A free PSA test may be requested if the PSA is between 4.0 and 10.0 ng/ml. If the test shows a low level of free PSA (usually less than 15 percent to 20 percent), biopsy is often the next step. If that biopsy turns out negative, it s common for the health provider to ask the patient to come back for another biopsy in six months or a year. This is because a low level of free PSA means something may be going on that bears watching. However, a man who is found to have a high percentage of free PSA is not guaranteed to be without prostate cancer. In some cases, a biopsy of a nodule may turn up prostate cancer despite a low overall total PSA and a high level of free PSA. 31 PSA Density Larger prostates tend to produce more PSA simply because there s more glandular tissue to create that enzyme. This means that more PSA is available to escape into the blood. If the patient has a large prostate, an elevated PSA level may arouse less suspicion of prostate cancer. The problem with this reasoning is that a cancer can easily be overlooked in men with larger prostates. In short, most studies have shown that the PSA itself is more predictive of prostate cancer than PSA density. For this reason, PSA density is not used in deciding whether to do a biopsy. 35 Prostate specific antigen density of the transition zone is a mathematical calculation. Two pieces of information are needed to arrive at this number. First is the PSA level, expressed in ng/ml. Second is the size of the central nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 24

25 portion of prostate measured in cubic centimeters; this measurement is achieved by using an ultrasound probe. The PSA value is divided by the measured volume. While some institutions have suggested that an upper limit of 0.15 correlates to a higher incidence of cancer and may signal the need for biopsy, very few institutions in the U.S. use it because it is a complex and expensive test. 36 PSA Velocity Prostate specific antigen velocity is the rate at which PSA rises over time. If the PSA rise is less than 0.75 ng/ml in a given year, it is typically not worrisome. However, a PSA level that rises faster than that hints at something unusual. If a PSA has climbed more than 0.75 ng/ml in less than a year regardless of the absolute level of PSA, the health provider may call for further testing. 37 Factors Affecting PSA Levels Ejaculation can increase the PSA level in the some men. The increase, however, is usually minimal and the PSA usually returns to normal within 48 hours. If a man wants to minimize the risk of his PSA being elevated, he should avoid ejaculation for a few days before the PSA test. Infection of the prostate can cause inflammation and elevate the PSA level. The usual symptoms of a prostate infection are increased urinary frequency and discomfort in the pelvis. Prostate infections are sometimes hard to diagnose. 38 While a urinalysis is the best test to evaluate an infection of the bladder, it may not detect infection of the prostate. In other words, a negative urinalysis does not mean the prostate is not infected. A second step is often a massage of the prostate to express fluid, which is then examined microscopically for signs of infection. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 25

26 If the health provider still suspects an infection in the prostate, an antibiotic may be prescribed. The medication will kill the offending bacteria, and the PSA level should decrease in several weeks to months. If the PSA does not decrease, a biopsy may be recommended. Amount and Frequency of PSA Testing It is important to find out if something other than cancer is causing the PSA increase. If infection or inflammation is not causing the PSA rise, a biopsy is the usual next step. If this biopsy is negative and the PSA remains elevated, a repeat biopsy may be recommended, often taking a larger number of biopsy samples. If the repeat biopsy is again negative, the patient will usually undergo repeat PSA tests at 6- to 12-month intervals. The health provider may recommend subsequent biopsies based on changes in PSA, changes in the digital rectal exam, or the provider s level of concern. 36 Prostatic Acid Phosphatase An older test, prostatic acid phosphatase (PAP), measures another enzyme produced by the prostate. Although some men with prostate cancer have increased amounts of prostatic acid phosphatase, this test is not nearly as good at picking up early prostate cancer as the PSA test. That s why PAP is rarely used anymore as a screening method. It is true that a high PAP level can signal locally advanced or metastatic disease in men who have already been diagnosed with prostate cancer. But other factors, such as a PSA level and the Gleason score (explained later), are generally better predictors of the cancer s extent than PAP. 39 nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 26

27 Tissue Tests The vast majority of patients with early stage prostate cancer do not have symptoms, which is why getting both regular PSA tests and DREs is important. If the PSA level and the DRE are both normal, there s little need for additional testing because the chance of a positive biopsy under these conditions is very low. That being said, up to 25 percent of prostate cancers do not cause a PSA elevation. These may be high-grade (meaning fastergrowing) tumors that have lost the ability to produce PSA like their normal prostate cell counterparts. That s why there s no increase in PSA. A nodule or firmness may be the only way to detect these types of tumors. This is just one more example of why DREs and PSA tests are used together. In these instances, tissue testing is typically required to determine if cancer is present. 31 A biopsy simply means removing and microscopically examining several pieces of tissue from the prostate. Most medical providers use an ultrasound guided technique for prostate biopsies, which involves inserting an ultrasound probe into the rectum to view the prostate. This may be slightly uncomfortable but it s usually not painful. 40 Using a guide that s attached to the probe, the provider directs the needle to a specific area and then triggers the rapid, automated biopsy unit. The needle removes a very small core of tissue in a split second. Separate needle sticks remove 6 to 12 samples (called core biopsies) in rapid succession. Many providers today use local anesthesia around the prostate to minimize pain from a biopsy. The entire biopsy process lasts only a few minutes and most men experience few side effects. Common minor side effects are a small amount of bleeding from the rectum or urine and blood in the semen. nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 27

28 It s important to recognize that small amounts of blood in the semen can persist for several weeks. 41 To reduce the risk of bleeding, it is usually recommended that patients avoid aspirin, anticoagulants such as warfarin, and nonsteroidal anti-inflammatory medications such as ibuprofen for a week prior to the biopsy. The provider might also prescribe antibiotics to reduce the chance of infection following the biopsy. 42 There is no best number of biopsy cores, but initial studies a number of years ago considered sextant biopsies (six cores) standard. Sextant biopsies remove samples from the base, mid-gland, and apex on both left and right lobes of the prostate. Many studies now show that increasing the number of cores from six to ten or twelve will identify more men with significant prostate cancer. These additional samples usually come from the outside edges of the gland. If it is suspected that the cancer is in the front (anterior) or central part of the gland, one or two samples may be taken from this area, too. Taking these additional cores has the advantage of reducing the risk of missing important cancer. Plus, these additional cores may reduce the need for a repeat biopsy if this first biopsy turns out to be negative. 43 In about 75 percent of men with an elevated PSA, the biopsy will be negative. For some of these men, however, a number of circumstances may lead to the recommendation of a repeat biopsy. The risk factors may include (1) a worrisome DRE, (2) a clearly elevated PSA, (3) a rising PSA, (4) a strong family history of prostate cancer, and (5) precancerous changes found in the first biopsy. When the biopsy should be repeated is a matter of some debate. Certainly the greater the concern about prostate cancer risk, nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com 28