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MEDICINE This text is a translation from the original German which should be used for referencing. The German version is authoritative. cme: Early Detection of Prostate Cancer Christof Börgermann, Herbert Rübben SUMMARY Introduction: Prostate cancer is the commonest cancer in men. Only the early stages are curable. Screening is aimed at identifying cancers confined to the prostate. Methods: Discussion of screening in the light of the interdisciplinary guideline and recent literature. Results: Screening is performed annually from the age of 50, ceasing at a life expectancy of less than 10 years. The digital-rectal examination is supplemented by PSA assay. Prior to the first PSA test informed consent must be obtained, with full discussion of biopsy and treatment options. A threshold of 4.0 ng/mL is defined as indication for prostate biopsy. Imaging methods do not outperform screening for prostate cancer. Discussion: Early detection identifies many latent prostate cancers and patients are at risk of overtreatment. A possible solution is to abandon the current single threshold value for PSA, in favour of Dtsch Arztebl 2006; 103(37): A 2399–406. the evaluation of trends in PSA values. Key words: prostate cancer, early detection, prostate-specific antigen (PSA), digital-rectal examination (DRE), transrectal Ultrasound (TRUS), biopsy P opulation-based screening for the detection of prostate cancer is defined as the testing of asymptomatic men at risk of having the disease. Population-based screening is performed on the initiative of the physician, rather than the patient, unlike so-called opportunistic screening, which is initiated by the patient. Prostate cancer is asymptomatic in its early stages; only later on does it produce clinical manifestations such as pain, hematuria, disturbances of urination, or rectal infiltration. There is a high chance of cure only when the disease is discovered early, while it is still asymptomatic. Screening for prostate cancer has not yet been conclusively shown to be effective, in the sense of reducing mortality. Two large randomized studies addressing this issue are currently in progress, the PLCO study ("Prostate, Lung, Colorectal, and Ovary") in the USA and the ERSPC study ("European Randomized Screening for Prostate Cancer") in Europe (1). Data from both studies, comparing the mortality from prostate cancer in screened men versus unscreened controls, will presumably be available in 2008. Even though these data are not yet in, there is already a broad consensus among physicians that screening for prostate cancer with a PSA (prostate-specific antigen) test and digital rectal examination should be provided to all men who request it, after they have given their informed consent (2). Epidemiology Prostate cancer is an illness of old age; it rarely arises in men under age 50 (3). It is the most common type of newly diagnosed cancer and the second most common cause of death from cancer in men. Roughly 12,000 men die of prostate cancer in Germany every year (4). Because the population as a whole is growing older, the diagnosis and treatment of prostate cancer will take on increasing importance in the years to come. By 2050, the number of persons over age 60 in Germany is expected to rise to 28 million, which will be 37% of the population, or double the current percentage. Klinik und Poliklinik für Urologie, Kinderurologie und Urologische Onkologie des Universitätsklinikum Essen (Dr. med. Börgermann, Prof. Dr. med. Dr. h. c. Rübben) Population-based screening The effectiveness of population-based screening for prostate cancer is unproven. In Germany, population-based screening for prostate cancer is not performed. Dtsch Arztebl 2006; 103(37): A 2399–406 ⏐ www.aerzteblatt.de 1 MEDICINE The current status of screening Population-based screening for prostate cancer is now performed only in scientific studies because the available data do not yet support its universal application. Nonetheless, screening on request is part of routine clinical practice in many countries. The current interdisciplinary consensus in Germany (5) recommends annual screening for prostate cancer in all men over age 50, or age 45 if there is a family history of the disease. The last screening is generally performed at age 75, though screening is still recommended for men over age 75 whose life expectancy is long. Life expectancy can be estimated with the aid of various normograms or algorithms that are available on the Internet; the normograms of Albertsen et al. (6) have been found useful in this group of patients. Digital rectal palpation alone is not an adequate screening method for prostate cancer and is therefore performed in combination with measurement of the PSA concentration. Before the first PSA level is obtained, the patient must be informed of the diagnostic and therapeutic measures that might be recommended afterward depending on the result, including prostatic biopsy and treatment of prostate cancer, and of the risks of these procedures. An elevated PSA level should be confirmed by repeated testing. Possible sources of error, both outside and inside the laboratory, should be considered and eliminated. Various factors can affect the measured PSA level and render its interpretation more difficult: circadian variation (up to 30%), instability of the sample (transport time? temperature? serum or whole blood?), external factors, differences between PSA testing systems, and calibration. A PSA level of 4.0 ng/ml or higher is currently considered an indication for further investigation with an ultrasound-guided biopsy under antibiotic coverage. Tissue specimens are taken with a punch at the sites where tumors are most commonly found, i.e., mainly laterally. At least six specimens are taken; the number depends on the size of the prostate, as determined by transrectal ultrasonography. The greater the number of specimens, the higher the chance of detecting prostate cancer. A second biopsy with at least six tissue specimens is performed within six months, after the exclusion of all intra- and extraprostatic sources of artifact, in the following situations: if the findings of the first biopsy are questionable or inconclusive, if no cancer was found despite a persistently elevated or rising PSA level, or if the first biopsy yielded a histological finding of a high grade PIN (prostatic intraepithelial neoplasia) or ASAP (atypical small acinar proliferation). Antibiotics are given for two weeks before the second biopsy, and the PSA level is then measured once again, so that infection can be ruled out as a cause of an elevated PSA level (Diagram 1). The recommendations outlined above, based on the current guidelines, are under intense discussion at present; revised recommendations will be published in the next edition of the guidelines. Digital rectal examination Digital rectal examination (DRE) of the prostate is a basic and cost-effective component of screening for prostate cancer. It has been a recommended procedure since 1971, the year the German screening program was introduced. Nonetheless, its effectiveness is open to question. No more than 10 to 15% of prostate cancers with a PSA level below 4.0 ng/ml can be detected by DRE (7). DRE is thus not a sensitive test, yet the predictive value of a positive DRE, when the PSA level is below 4.0 ng/ml, is high. Most prostate cancers detected in this way fulfill the criteria for a clinically significant tumor, and they would have remained undetected had DRE not been performed (8). A disadvantage of DRE is that suspicious palpatory findings are associated with cancer that has spread beyond the prostate in 40 to 70% of cases (regardless of the PSA level) and may therefore no longer be curable. Current status of screening Screening from age 50 onward, or from age 45 in men with a positive family history. A PSA level above 4 ng/ml is an indication for a biopsy. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 2 MEDICINE DIAGRAM 1 Algorithm for prostate cancer screening (S3-guidelines [5]) *1from age 45 onward in patients with positive family history Transrectal ultrasonography Transrectal ultrasonography (TRUS) of the prostate is more expensive than DRE and requires special equipment and training. It is also not universally available. It was thought, at first, that the use of TRUS to search for echo-poor areas in the prostate might be a good means of prostate cancer screening, but enthusiasm waned in the light of further data. As Transrectal ultrasonography Transrectal ultrasonography is more expensive than DRE and requires special equipment and training. It is, however, an indispensable part of the technique of prostatic punch biopsy. Treatment algorithm Patients with PSA > 4 ng/ml and/or a suspect finding for tumor on DRE should undergo an ultrasound-guided punch biopsy of the prostate. Patients with normal results should continue to have their PSA checked annually. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 3 MEDICINE reported in an interdisciplinary consensus statement (5), a number of studies have documented the inadequate ability of TRUS to detect localized prostate cancer when used as a screening technique (9, 10). Recently, attempts have been made to improve the sensitivity and specificity of TRUS with technical innovations including color-coded duplex ultrasonography, high-resolution Doppler ultrasonography, ultrasonographic contrast media, B-image harmonic ultrasonography, 3D reconstruction, and the use of neural networks such as "computed TRUS" (11, 12). The current recommendations of the American Cancer Society and the European Association of Urology recognize that TRUS has a role in the diagnostic evaluation of prostate cancer, but the question of its use in screening remains open. Its most important application is during the performance of ultrasound-guided punch biopsy of the prostate. It enables both the systematic removal of cylindrical tissue specimens, and the targeted sampling of suspect areas. Punch biopsy of the prostate According to the current guidelines, any suspect findings on digital rectal examination, and/or a PSA level that is above 4 ng/ml for unexplained reasons, are considered an indication for punch biopsy of the prostate (provided that the patient's current quality of life and life expectancy are such that a positive biopsy would be followed by treatment). Punch biopsy under transrectal ultrasonic guidance is the internationally established standard. Depending on the size of the organ, at least three tissue samples are taken at various sites in each of the two prostatic lobes (13). The biopsy must be performed under antibiotic coverage, preferably with a gyrase inhibitor. The complications described in the literature include hematuria for more than three days (22%), hemospermia (50%), fever (3.5%), and urosepsis requiring hospitalization (0.5%) (14). Prostate-specific antigen The introduction of routine determination of prostate-specific antigen levels in the late 1980's was a revolutionary development in the early detection of prostate cancer. Screening with PSA levels led to an overall shift in the stage of prostate cancer at the time of detection, from a later to an earlier stage (15). In the pre-PSA era, two-thirds of all prostate cancers had spread beyond the prostate by the time of detection and were thus no longer curable. Two-thirds of all prostate cancers are now detected while still confined to the prostate (16, 17). In the USA, the first country in which PSA testing was used for screening, the mortality from prostate cancer has fallen since 1991. It is unknown whether this drop is actually due to more frequent detection in the potentially curable stage when the tumor is confined to the prostate, or to improvements in therapy, or both. This question will only be answerable when the results of the large-scale studies of screening for prostate cancer become available in 2008 (1). PSA is an organ-specific rather than tumor-specific marker. The serum PSA level can be influenced not only by malignancy, but by numerous other factors as well: > medications such as finasteride, luteinizing hormone releasing hormone (LHRH) analogues, and antiandrogens, > prostatic diseases such as acute or chronic prostatitis, benign prostatic hyperplasia (BPH), and urinary retention, > and urological manipulations such as prostatic punch biopsy and digital rectal examination (18). Large-scale studies have shown that the PSA level is below 4 ng/ml in 80 to 85% of men presenting for screening, between 4 and 10 ng/ml in 10 to 15%, and above 10 ng/ml in 2 to Prostatic punch biopsy The established standard is a punch biopsy under transrectal ultrasonographic guidance. The potential complications include infection, sepsis, hematuria, and hemospermia. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 4 MEDICINE DIAGRAM 2 Distribution of PSA values in 11,656 men who presented for prostate cancer screening. TABLE 1 TABLE 2 The frequency of biopsy-proven prostate cancer as a function of the PSA level The relation between prostatespecific antigen and tumor stage PSA (ng/mL) Percentage of tumors in stage = pT2(%) *1 6,6 2,5–4,0 78–83 0,6–1,0 10,1 4,1–6,0 74–81 1,1–2,0 17,0 6,1–8,0 71–78 2,1–3,0 23,9 8,1–10,0 67–75 3,1–4,0 26,9 >10,0 49–57 4,0–9,9 27,9 >10,0 57,6 PSA (ng/mL) Frequency of prostate cancer (%) < 0,5 *1Percentage of tumors that are confined to the prostate among patients with PSA in the indicated ranges (Carter 1999) (Thompson 2003 & ERSPC Rotterdam) 5% (Diagram 2). Prostate cancer is found in up to 15% of men with levels below 4 ng/ml, about 25% of men with levels between 4 and 10 ng/ml, and over 50% of men with levels above 10 ng/ml (Diagram 3, Table 1). In the last-named group, the very high PSA level is often associated with spread of the tumor beyond the prostate. Table 2 shows the percentage of detected prostatic tumors that are confined to the prostate, and therefore curable, as a function of the PSA level (20). Studies are currently underway to determine whether the diagnostic value of PSA testing can be improved by the use of PSA isoforms, such as the f/tPSA ratio and cPSA, or by the use of different norms for PSA levels depending on age Prostate-specific antigen Currently, because of PSA testing, nearly 70% of prostate cancers can be detected in a curable stage. The serum PSA concentration can be influenced by numerous factors other than cancer. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 5 MEDICINE DIAGRAM 3 DIAGRAM 4 Course of PSA over 10 years. Patients in whom no tumor is found have nearly constant PSA levels, while in those with prostate cancer the PSA level rises steadily over time. Biopsy findings of patients with PSA levels between 4 and 10 ng/ml. A carcinoma is found in only one-quarter of all cases; two-thirds of all biopsies yield normal findings. and prostatic volume. Although these newer techniques have been found to lower the need for biopsy substantially, they have not yet found their way into routine clinical practice. PSA-based screening is currently controversial. In the USA, roughly 226 per 100,000 men over age 65 die of prostate cancer every year. Autopsy studies have shown, however, that as many as 80% of 70-year-olds have latent prostate cancer, i.e., tumors that will not cause death. It is feared that PSA-based screening will lead to the detection of large numbers of clinically insignificant tumors (13). The dilemma of screening is that its aim is precisely to find tumors that are small and confined to the prostate, because these tumors have the greatest chance of cure (21). According to the findings of a Scandinavian study, about 15% of men with prostate cancer who are treated with radical prostatectomy will develop distant metastases within 10 years, as opposed to about 25% of untreated patients (22). This means that, in about 75% of patients with known prostate cancer who are merely observed, there will be no systemic progression of disease for 10 years after the diagnosis, and the chance that systemic progression will develop is only 10% higher than in patients who undergo radical prostatectomy. On the one hand, these findings confirm the fear that many clinically insignificant tumors will be detected and treated; on the other hand, they also confirm that 85% of patients do not develop systemically progressive disease after treatment, and this figure is 10% higher than in untreated patients. Imaging studies Visualization of the prostate with currently available techniques such as computerized tomography, magnetic resonance imaging, and the imaging methods of nuclear medicine is Imaging studies "Computed TRUS": a computer program is used to make otherwise invisible information visible through color-coding. Histological sections of the prostate are correlated with ultrasonic images from the same patient. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 6 MEDICINE BOX 1 Screening for Prostate Cancer At present Beginning at: Ending at: Screening interval: Biopsy indication: Possible future recommendations Age 50 Age 40 When remaining life expectancy < 10 years 1 year 2 years* PSA = 4 ng/ml PSA threshold rising by 0.5 ng/ml/year *as long as PSA < 2 ng/ml, otherwise annually BOX 2 Potential "savings" in comparison with the current screening regime* Screening interval: PSA tests: Biopsies: Surgery/radiation: Every two years from age 40 onward ~ 35 % ~ 25 % ~ 12 % *i.e., standard screening according to (24) inadequate for the early detection of prostate cancer. The same is true, at present, for 11Ccholine-PET/CT. These techniques currently have no application in screening for prostate cancer. Future prospects for PSA-based screening New guidelines for screening for prostate cancer are now under development and will have to take the major criticisms of PSA-based screening into account: > the large number of unnecessary PSA determinations, > the large number of unnecessary prostatic biopsies, > and the large number of unnecessary treatments for prostate cancer, as the disease will often remain stable even if untreated, but can also progress even if treated. The number of unnecessary PSA determinations might be lowered by a longer interval between tests. The interval between a positive test and the time that the diagnosis would have been made if this test had not been performed is called the "leadtime." Screening for prostate cancer with PSA is associated with a leadtime of 5 to 10 years. In the ERSPC study, which included 8,350 patients, biopsies were performed for PSA values above a threshold of 3 ng/ml. This resulted in the diagnosis of 412 carcinomas of the prostate. After a testing interval of 48 months, 18 additional carcinomas were detected, all of which were in the T1 or T2 stage and therefore potentially curable (23). The available data do not currently allow a determination of the optimal interval for PSA testing, but annual screening for patients whose PSA values are low no longer seems reasonable. Prolonging the interval would reduce the number of PSA tests and biopsies performed, thereby not only lowering the total cost but also limiting unnecessary impairment of the patients' quality of life. One study, in which patients with prostate cancer confirmed by prostatic punch biopsy were actively observed, reveals several possible ways of reducing the number of un- PSA-based screening Prostate cancer is present in up to 15% of men with PSA levels below 4 ng/ml, about 25% of men with levels between 4 and 10 ng/ml, and over 50% of men with levels above 10 ng/ml. Levels above 10 ng/ml are often associated with spread of disease beyond the prostate. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de Major criticisms – Large number of unnecessary PSA tests – Large number of unnecessary biopsies – Large number of unnecessary treatments 7 MEDICINE necessary diagnostic tests and treatments. 299 patients considered to be at low risk of developing further progression of their prostate cancer were not treated, but actively observed. This meant, in practice, that curative treatment was held in reserve until the moment that the tumor was seen to be starting to progress. The patients were all over 70 years old and had PSA levels below 15 ng/ml, tumor stage cT2b or better, and Gleason scores below 7. (Note: The Gleason score has been used since the 1970's and is a measure of the aggressiveness of prostate carcinoma based on histological features, i.e., a method of tumor grading. The higher the Gleason score, the more aggressive the tumor. The two most common tissue patterns seen under the microscope are assigned scores from 1 to 5, and these scores are then added together to generate a Gleason score from 2 to 10). Progression was defined by various criteria, among which was a PSA doubling time of less than two years. After a median follow-up of 55 months, the disease-specific survival was 99%. 60% of patients had no progression and remained under active observation (24). It follows that the dynamics of PSA levels can be exploited in an early detection program to lessen the number of biopsies and avoid unnecessary impairment of the patients' quality of life. If a PSA doubling time of less than two years were to be generally used as a criterion for the performance of punch biopsies, then patients like the 60% percent of men in the study who remained in the observation group would not have to undergo a biopsy, would not learn their (clinically irrelevant) diagnosis, and would therefore benefit from a better quality of life. The time course of the PSA level provides an indication of the aggressiveness of prostate cancer (Diagram 4). If dynamic PSA testing is to be performed, then the initial PSA level must be measured at an earlier age than the current guidelines recommend, i.e., at an age when the risk of prostate cancer is minimal, so that the first value can serve as a baseline for the detection of possible future increases. The intelligent use of dynamic PSA testing prior to invasive diagnostic studies might help distinguish patients requiring early treatment from others who probably harbor clinically insignificant tumors. The concept of the rate of increase of PSA has been under study for many years, but no definitive recommendations for dynamic testing can be made at present. Conclusion PSA-based screening for prostate cancer might, in the future, look something like this: testing would begin at age 40 and end when the patient's predicted life expectancy becomes less than 10 years. Unnecessary testing could be avoided by prolonging the interval between PSA tests to 2 years for patients whose PSA level is less than 2 ng/ml. The use of a rigid PSA threshold of 4 ng/ml for prostatic punch biopsy might give way to a more dynamic approach, e.g., a threshold that rises by 0.5 ng/ml per year (see Boxes 1 and 2). Conflict of Interest Statement The authors declare that no conflict of interest exists according to the Guidelines of the International Committee of Medical Journal Editors. Manuscript received on 19. April 2006, final version accepted on 17. Juli 2006. Translated from the original German by Ethan Taub, M.D. REFERENCES 1. De Koning HJ, Liem MK, Baan CA et al.: Prostate cancer mortality reduction by screening: power and time frame with complete enrollment in the European Randomised Screening for Prostate Cancer (ERSPC) trial. Int J Cancer 2002; 98: 268–73. 2. Schmid HP, Riesen W, Prikler L: Update on screening for prostate cancer with prostate-specific antigen. Crit Rev Oncol Hematol 2004; 50: 71–8. 3. Pienta KJ: Etiology, epidemiology and prevention of carcinoma of the prostate. In: Walsh PC, Retik A, Stamey TA, Vaughan EJ, Hrsg.: Campell´s Urology. Philadelphia: Saunders, 1997: 2489–96. Biopsy findings Among men with PSA levels between 4 and 10 ng/ml, biopsy reveals prostate cancer in only one-quarter of all cases. Proposal The elimination of a rigid PSA threshold in favor of a more dynamic view of PSA levels might help reduce the number of unnecessary diagnostic and therapeutic procedures and thereby improve patients' quality of life. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 8 MEDICINE 4. Statistisches Bundesamt. www.destatis.de/basis/d/gesu/gesutab20.php 5. Fachgesellschaften (2002): AWMF: S3-Leitlinie: PSA-Bestimmung in der Prostatakarzinomdiagnostik (Früherkennung des Prostatakarzinoms). www.awmf-online.de. 6. Albertsen PC, Fryback DG, Storer BE, Kolon TF, Fine J: The impact of co-morbidity on life expectancy among men with localized prostate cancer. J Urol 1996; 156: 127–32. 7. Luboldt H, Rubben H: PSA – Früherkennung des Prostatakarzinoms. Urologe A 2000; 39: 22–6. 8. Carvalhal GF, Smith DS, Mager DE, Ramos C, Catalona WJ: Digital rectal examination for detecting prostate cancer at prostate specific antigen levels of 4 ng/mL or less. J Urol 1999; 161(3): 835–9. 9. Ellis WJ, Chetner MP, Preston SD, Brawer MK: Diagnosis of prostatic carcinoma: the yield of serum prostate specific antigen, digital rectal examination and transrectal ultrasonography. J Urol 1994; 152: 1520–5. 10. Flanigan RC, Catalona WJ, Richie JP et al.: Accuracy of digital rectal examination and transrectal ultrasonography in localizing prostate cancer. J Urol 1994; 152:1506–9. 11. Loch T, Leuschner I, Genberg C et al.: Improvement of transrectal ultrasound. Artificial neural network analysis (ANNA) in detection and staging of prostatic carcinoma. Urologe A 2000; 39: 341–7. 12. Loch T, Eppelmann U, Lehmann J, Wullich B, Loch A, Stockle M: Transrectal ultrasound guided biopsy of the prostate: random sextant versus biopsies of sono-morphologically suspicious lesions. World J Urol 2004; 22: 357–60. 13. Brawer MK, Chetner MP: Ultrasonography and biopsy of the prostate. In: Walsh PC, Retik A, Stamey TA, Vaughan EJ, eds.: Campell´s Urology. Philadelphia: Saunders, 1997: 2506–18. 14. Raaijmakers R, Kirkels WJ, Roobol MJ, Wildhagen MF, Schroder FH: Complication rates and risk factors of 5802 transrectal ultrasound-guided sextant biopsies of the prostate within a population-based screening program. Urology 2002; 60(5): 826–30. 15. Hoedemaeker RF, Rietbergen JB, Kranse R, Schroder FH, van der Kwast TH: Histopathological prostate cancer characteristics at radical prostatectomy after population based screening. J Urol 2000; 164(2): 411–15. 16. Catalona WJ, Smith DS, Wolfert RL et al.: Evaluation of percentage of free serum prostate-specific antigen to improve specificity of prostate cancer screening. JAMA 1995; 274: 1214–20. 17. Luboldt HJ, Altwein JE, Bichler KH, Czaja D et al.: Early recognition of prostate carcinoma. Initial results of a prospective multicenter study in Germany. Project Group for Early Detection DGU-BDU Laboratory diagnosis Professional Circle. Urologe A 1999; 38(2):114–23. 18. Price CP, Allard J, Davies G et al.: Pre- and post-analytical factors that may influence use of serum prostate specific antigen and its isoforms in a screening programme for prostate cancer. Ann Clin Biochem 2001; 38 (Pt 3): 188–216. 19. Thompson IM, Goodman PJ, Tangen CM et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349: 215–24. 20. Carter HB, Epstein JI, Partin AW: Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease. Urology 1999; 53:126–30. 21. Catalona WJ, Loeb S: The PSA era is not over for prostate cancer. Eur Urol 2005; 48: 541–5. 22. Bill-Axelson A, Holmberg L, Ruutu M, Haggman M, Andersson SO, Bratell S et al.: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2005; 352:1977–84. 23. Van der Cruijsen-Koeter IW, van der Kwast TH, Schroder FH: Interval carcinomas in the European Randomized Study of Screening for Prostate Cancer (ERSPC)-Rotterdam. J Natl Cancer Inst 2003; 95:1462–6. 24. Klotz L: Active surveillance with selective delayed intervention: using natural history to guide treatment in good risk prostate cancer. J Urol 2004; 172: 48–50. Corresponding author Dr. med. Christof Börgermann Klinik und Poliklinik für Urologie, Universitätsklinik Essen Hufelandstr. 55, 45122 Essen, Germany [email protected] FURTHER INFORMATION This article has been certified by the North Rhine Academy for Postgraduate and Continuing Medical Education. The Deutsches Ärzteblatt provides certified continuing medical education (CME) in accordance with the requirements of the Chambers of Physicians of the German federal states (Länder). CME points of the Chambers of Physicians can be acquired only through the Internet by the use of the German version of the CME questionnaire within 6 weeks of publication of the article. See the following website: www.aerzteblatt.de/cme. Participants in the CME program can manage their CME points with their 15-digit "uniform CME number" (einheitliche Fortbildungsnummer, EFN). The EFN must be entered in the appropriate field in the www.aerzteblatt.de website under "meine Daten" ("my data"), or upon registration. The EFN appears on each participant's CME certificate. Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 9 MEDICINE Please answer the following questions to participate in our certified Continuing Medical Education program. Only one answer is possible per question. Please select the answer that is most appropriate. Question 1 Screening for the detection of prostate cancer is defined as a) b) c) d) e) Testing all men with the disease Testing all healthy men Testing asymptomatic men at risk for the disease Testing symptomatic men at risk for the disease Testing asymptomatic or symptomatic men at risk for the disease at their own request Question 2 Approximately how many men die of prostate cancer in Germany every year? a) b) c) d) e) 9,000 12,000 15,000 18,000 21,000 Question 3 A patient comes to your office and says his father died of prostate cancer. Screening is recommended for this patient starting at what age? a) b) c) d) e) 40 45 50 55 immediately on presentation, regardless of age Question 4 What threshold value of PSA is now considered an indication for prostatic biopsy? a) b) c) d) e) 2.5 ng/ml 3.0 ng/ml 3.5 ng/ml 4.0 ng/ml 4.5 ng/ml Question 5 Which of the following is NOT a typical complication of an ultrasound-guided transrectal sextant biopsy? a) b) c) d) e) urosepsis prostatitis hemospermia hematuria retrograde ejaculation Question 6 What percentage of screened patients have a normal PSA level (i.e., < 4 ng/ml)? a) b) c) d) e) 20% 40% 60% 80% 100% Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 10 MEDICINE Question 7 What percentage of patients with a PSA level between 4 and 10 ng/ml will go on to have a finding of prostate cancer on punch biopsy? a) b) c) d) e) 0-10% 10-20% 20-30% 30-40% 40-50% Question 8 A latent prostate cancer is found at autopsy in what percentage of men over age 70? a) b) c) d) e) up to 100% up to 80% up to 60% up to 40% up to 20% Question 9 Which of the following imaging techniques is used in screening for prostate cancer? a) b) c) d) e) MRI CT Bone scan PET-CT None of the above Question 10 Distant metastases are seen less commonly 10 years after diagnosis in patients who were treated by radical prostatectomy than in patients who were merely observed. How great is the difference between the prevalences of metastatic disease in these two patient groups? a) b) c) d) e) 10% 20% 30% 40% 50% Important Information This text is a translation from the original German which should be used for referencing. The German version is authoritative. The Deutsches Ärzteblatt provides certified continuing medical education (CME) in accordance with the requirements of the Chambers of Physicians of the German federal states (Länder). CME points of the Chambers of Physicians can be acquired only through the Internet by the use of the German version of the CME questionnaire within 6 weeks of publication of the article. See the following website: www.aerzteblatt.de/cme. The correct answers to this CME questionnaire will be published in Issue 45/2006 under this heading. The planned CME topic in Issue 41/2006 is "The diagnosis and treatment of neuropathic pain." Dtsch Arztebl 2006; 103(37): A 2399–406 www.aerzteblatt.de 11