Das Niedrig-Risiko-Prostatakarzinom – Strategien zur Reduktion von Überdiagnose und Übertherapie

Zusammenfassung

Das Prostatakarzinom (PCa) ist die häufigste Krebserkrankung des Mannes in Deutschland. Im Gegensatz zu einer jährlich steigenden Neuerkrankungsrate ist die PCa-spezifische Sterberate konstant bzw. leicht rückläufig und beträgt aktuell etwa 3 – 4 %. Diese Entwicklungen sind unter anderem auf die seit Ende der 80er-Jahre im Rahmen der Früherkennung durchgeführte Blutwertbestimmung des prostataspezifischen Antigens (PSA) und verbesserte bildgebende Verfahren bzw. Biopsietechniken zurückzuführen. Tatsächlich wird heute die Mehrzahl der Patienten mit PCa in frühen, organbegrenzten und somit kurativen Stadien entdeckt. Zu diesen gehören auch die sogenannten „klinisch nicht signifikanten“ Karzinome (Niedrig-Risiko-Karzinome), die aufgrund ihrer wenig aggressiven Tumorbiologie einen langsamen klinischen Verlauf aufweisen. Daher leiden wenige der davon betroffenen Patienten im Verlauf der Erkrankung unter krebsspezifischen Beschwerden bzw. versterben ursächlich am PCa. Im Gegensatz dazu ist jede aktive Therapie (z. B. Operation oder Bestrahlung) mit spezifischen Risiken (z. B. Inkontinenz, Impotenz, Strahlenzystitis bzw. -proktitis) behaftet, sodass eine sorgfältige Risiko-Nutzen-Abwägung erfolgen muss. Die Gründe für die breite Indikation zu einer aktiven Therapie liegen vor allem in den mangelnden Kenntnissen der Tumorbiologie und der Angst ein Hoch-Risiko-Karzinom „zu verpassen“. Aktuell gibt es jedoch für das frühe, Niedrig-Risiko-PCa keine Evidenzgrad-1-Empfehlung hinsichtlich einer bestimmten Therapie. Das Therapiekonzept der so-genannten aktiven Überwachung (active surveillance [AS]) hat aktuell ein äquivalentes Tumorüberleben der Niedrig-Risiko-PCa-Patienten gezeigt. Dieses Konzept basiert auf seriellen klinischen Untersuchungen, die es erlauben, den Patienten über einen Zeitraum zu beobachten, um bei Veränderung des PCas, z. B. PSA-Anstieg oder Gleason-Score-Progress in den Kontrollbiopsien, eine aktive Therapie rechtzeitig einzuleiten. Dadurch sollen den Patienten während des Überwachungszeitraums potenzielle Nebenwirkungen einer aktiven Therapie erspart und die Rate der Übertherapie minimiert werden. Diese AS-Therapie-Strategie bietet neben der individuellen auch auf gesellschaftlicher und gesundheits-ökonomischer Ebene Vorteile.

• Literatur

• 1 Robert Koch Institut B, Deutschland. Krebs in Deutschland – Prostata. Im Internet: http://www.krebsdaten.de/Krebs/DE/Content/Publikationen/Krebs_in_Deutschland/kid_2013/kid_2013_c61_prostata.pdf?__blob=publicationFile
• 2 Crawford ED, Grubb 3rd R, Black A et al. Comorbidity and mortality results from a randomized prostate cancer screening trial. J Clin Oncol 2011; 29: 355-361
• 3 Schroder FH, Hugosson J, Roobol MJ et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009; 360: 1320-1328
• 4 Hankey BF, Feuer EJ, Clegg LX et al. Cancer surveillance series: interpreting trends in prostate cancer--part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates. J Nati Cancer Inst 1999; 91: 1017-1024
• 5 Siegel R, Ma J, Zou Z et al. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9-29
• 6 Wilt TJ, Brawer MK, Jones KM et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203-213
• 7 Heidenreich A, Bellmunt J et al. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 2014; 65: 124-137
• 8 Gorin MA, Soloway CT, Eldefrawy A et al. Factors that influence patient enrollment in active surveillance for low-risk prostate cancer. Urology 2011; 77: 588-591
• 9 Bill-Axelson A, Holmberg L, Ruutu M et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364: 1708-1717
• 10 Statistisches Bundesamt W, Deutschland. Häufigste Todesursachen, 2014. 2014 Im Internet: https://www.destatis.de/DE/ZahlenFakten/GesellschaftStaat/Gesundheit/Todesursachen/Todesursachen.html
• 11 Etzioni R, Gulati R, Falcon S et al. Impact of PSA screening on the incidence of advanced stage prostate cancer in the United States: a surveillance modeling approach. Med Decis Making 2008; 28: 323-331
• 12 Jemal A, Ward E, Thun M. Declining death rates reflect progress against cancer. PloS one 2010; 5: e9584
• 13 Paquette EL, Sun L, Paquette LR et al. Improved prostate cancer-specific survival and other disease parameters: impact of prostate-specific antigen testing. Urology 2002; 60: 756-759
• 14 Sakr WA, Grignon DJ, Crissman JD et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo 1994; 8: 439-443
• 15 Sanchez-Chapado M, Olmedilla G, Cabeza M et al. Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: an autopsy study. Prostate 2003; 54: 238-247
• 16 Soos G, Tsakiris I, Szanto J et al. The prevalence of prostate carcinoma and its precursor in Hungary: an autopsy study. Eur Urol 2005; 48: 739-744
• 17 Delongchamps NB, Singh A, Haas GP. The role of prevalence in the diagnosis of prostate cancer. Cancer Control 2006; 13: 158-168
• 18 Klotz L. Active surveillance: patient selection. Curr Opin Urol 2013; 23: 239-244
• 19 Konety BR, Bird VY, Deorah S et al. Comparison of the incidence of latent prostate cancer detected at autopsy before and after the prostate specific antigen era. J Urol 2005; 174: 1785-1788 (discussion 8)
• 20 Lu-Yao GL, Albertsen PC, Moore DF et al. Outcomes of localized prostate cancer following conservative management. JAMA 2009; 302: 1202-1209
• 21 Albertsen PC, Hanley JA, Gleason DF et al. Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 1998; 280: 975-980
• 22 Chodak GW, Thisted RA, Gerber GS et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994; 330: 242-248
• 23 Etzioni R, Penson DF, Legler JM et al. Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends. J Nati Cancer Inst 2002; 94: 981-990
• 24 Loeb S, Bjurlin MA, Nicholson J et al. Overdiagnosis and overtreatment of prostate cancer. Eur Urol 2014; 65: 1046-1055
• 25 Yabroff KR, Lund J, Kepka D et al. Economic burden of cancer in the United States: estimates, projections, and future research. Cancer Epidemiol Biomarkers Prev 2011; 20: 2006-2014
• 26 Thompson IM, Ankerst DP, Etzioni R et al. It's time to abandon an upper limit of normal for prostate specific antigen: assessing the risk of prostate cancer. J Urol 2008; 180: 1219-1222
• 27 Urologie DGfr. Interdisziplinäre Leitlinie der Qualität S3 zur Früherkennung, Diagnose und Therapie der verschiedenen Stadien des Prostatakarzinoms. 2014 Im Internet: http://www.awmf.org/uploads/tx_szleitlinien/043-022OLl_S3_Prostatakarzinom_2014-12.pdf
• 28 Klotz L. Active surveillance for prostate cancer: for whom?. J Clin Oncol 2005; 23: 8165-8169
• 29 Kim 2nd S, Dall'Era MA, Evans CP. Economic analysis of active surveillance for localized prostate cancer. Curr Opin Urol 2012; 22: 247-253
• 30 Klotz L, Zhang L, Lam A et al. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010; 28: 126-131
• 31 Cooperberg MR, Broering JM, Carroll PR. Time trends and local variation in primary treatment of localized prostate cancer. J Clin Oncol 2010; 28: 1117-1123
• 32 Rosario DJ, Lane JA, Metcalfe C et al. Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within ProtecT study. BMJ 2012; 344: d7894
• 33 Bul M, Zhu X, Valdagni R et al. Active surveillance for low-risk prostate cancer worldwide: the PRIAS study. Eur Urol 2013; 63: 597-603
• 34 Steginga SK, Turner E, Donovan J. The decision-related psychosocial concerns of men with localised prostate cancer: targets for intervention and research. World J Urol 2008; 26: 469-474
• 35 Chism DB, Hanlon AL, Horwitz EM et al. A comparison of the single and double factor high-risk models for risk assignment of prostate cancer treated with 3D conformal radiotherapy. Int J Radiat Oncol Biol Phys 2004; 59: 380-385
• 36 Cooperberg MR, Carroll PR, Klotz L. Active surveillance for prostate cancer: progress and promise. J Clin Oncol 2011; 29: 3669-3676
• 37 Palisaar JR, Noldus J, Loppenberg B et al. Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. BJU Int 2012; 110: E172-E181
• 38 D'Amico AV, Whittington R, Malkowicz SB et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280: 969-974
• 39 Becker A, Seiler D, Kwiatkowski M et al. A comparative assessment of active surveillance for localized prostate cancer in the community versus tertiary care referral center. World J Urol 2014; 32: 891-897
• 40 Barocas DA, Cowan JE, Smith JA et al. What percentage of patients with newly diagnosed carcinoma of the prostate are candidates for surveillance? An analysis of the CaPSURE database. J Urol 2008; 180: 1330-1334 (discussion 4 – 5)
• 41 Hoffman RM, Hunt WC, Gilliland FD et al. Patient satisfaction with treatment decisions for clinically localized prostate carcinoma. Results from the Prostate Cancer Outcomes Study. Cancer 2003; 97: 1653-1662
• 42 Xu J, Neale AV, Dailey RK et al. Patient perspective on watchful waiting/active surveillance for localized prostate cancer. J Am Board Fam Med 2012; 25: 763-770
• 43 Pierorazio PM, Spencer BA, McCann TR et al. Preoperative risk stratification predicts likelihood of concurrent PSA-free survival, continence, and potency (the trifecta analysis) after radical retropubic prostatectomy. Urology 2007; 70: 717-722
• 44 van den Bergh RC, Essink-Bot ML, Roobol MJ et al. Do anxiety and distress increase during active surveillance for low risk prostate cancer?. J Urol 2010; 183: 1786-1791
• 45 Pickles T, Ruether JD, Weir L et al. Psychosocial barriers to active surveillance for the management of early prostate cancer and a strategy for increased acceptance. BJU Int 2007; 100: 544-551
• 46 Esserman LJ, Thompson IM, Reid B et al. Addressing overdiagnosis and overtreatment in cancer: a prescription for change. Lancet Oncol 2014; 15: e234-e242
• 47 Gann PH. Risk factors for prostate cancer. Rev Urol 2002; 4: S3-S10
• 48 Schiffmann J, Connan J, Salomon G et al. Tumor volume in insignificant prostate cancer: Increasing threshold gains increasing risk. Prostate 2015; 75: 45-49
• 49 Freedland SJ, Wen J, Wuerstle M et al. Obesity is a significant risk factor for prostate cancer at the time of biopsy. Urology 2008; 72: 1102-1105
• 50 Kim YM, Park S, Kim J et al. Role of prostate volume in the early detection of prostate cancer in a cohort with slowly increasing prostate specific antigen. Yonsei Med J 2013; 54: 1202-1206
• 51 Murphy AB, Akereyeni F, Nyame YA et al. Smoking and prostate cancer in a multi-ethnic cohort. Prostate 2013; 73: 1518-1528
• 52 Yli-Hemminki TH, Laurila M, Auvinen A et al. Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate-specific antigen (PSA) concentration in the Finnish prostate cancer screening trial. BJU Int 2013; 112: 735-741
• 53 Carignan A, Roussy JF, Lapointe V et al. Increasing risk of infectious complications after transrectal ultrasound-guided prostate biopsies: time to reassess antimicrobial prophylaxis?. Eur Urol 2012; 62: 453-459
• 54 Gallina A, Suardi N, Montorsi F et al. Mortality at 120 days after prostatic biopsy: a population-based study of 22,175 men. Int J Cancer 2008; 123: 647-652
• 55 Thompson IM, Pauler DK, Goodman PJ et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N Engl J Med 2004; 350: 2239-2246
• 56 Ahyai SA, Graefen M, Steuber T et al. Contemporary prostate cancer prevalence among T1c biopsy-referred men with a prostate-specific antigen level < or = 4.0 ng per milliliter. Eur Urol 2008; 53: 750-757
• 57 Thompson Jr IM, Leach RJ, Ankerst DP. Focusing PSA testing on detection of high-risk prostate cancers by incorporating patient preferences into decision making. JAMA 2014; 312: 995-996
• 58 Murphy DG, Ahlering T, Catalona WJ et al. The Melbourne Consensus Statement on the early detection of prostate cancer. BJU Int 2014; 113: 186-188
• 59 Schmid M, Trinh QD, Graefen M et al. The role of biomarkers in the assessment of prostate cancer risk prior to prostate biopsy: which markers matter and how should they be used?. World J Urol 2014; 32: 871-880
• 60 Hansen J, Auprich M, Ahyai SA et al. Initial prostate biopsy: development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay. Eur Urol 2013; 63: 201-209
• 61 Kranse R, Roobol M, Schroder FH. A graphical device to represent the outcomes of a logistic regression analysis. Prostate 2008; 68: 1674-1680
• 62 Thompson IM, Ankerst DP, Chi C et al. Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Nati ancer Inst 2006; 98: 529-534
• 63 Ankerst DP, Groskopf J, Day JR et al. Predicting prostate cancer risk through incorporation of prostate cancer gene 3. J Urol 2008; 180: 1303-1308 (discussion 8)
• 64 Ankerst DP, Hoefler J, Bock S et al. Prostate Cancer Prevention Trial risk calculator 2.0 for the prediction of low- vs high-grade prostate cancer. Urology 2014; 83: 1362-1367
• 65 Ankerst DP, Koniarski T, Liang Y et al. Updating risk prediction tools: a case study in prostate cancer. Biom J 2012; 54: 127-142
• 66 Heidenreich A, Bastian PJ, Bellmunt J et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol 2014; 65: 124-137
• 67 Simmons LA, Ahmed HU, Moore CM et al. The PICTURE study -- prostate imaging (multi-parametric MRI and Prostate HistoScanning) compared to transperineal ultrasound guided biopsy for significant prostate cancer risk evaluation. Contemp Clin Trials 2014; 37: 69-83
• 68 Boehm K, Salomon G, Beyer B et al. Shear wave elastography for localization of prostate cancer lesions and assessment of elasticity thresholds: Implications for targeted biopsies and active surveillance protocols. J Urol 2014;
• 69 Salomon G, Drews N, Autier P et al. Incremental detection rate of prostate cancer by real-time elastography targeted biopsies in combination with a conventional 10-core biopsy in 1024 consecutive patients. BJU Int 2014; 113: 548-553
• 70 Schiffmann J, Tennstedt P, Fischer J et al. Does HistoScanning predict positive results in prostate biopsy? A retrospective analysis of 1,188 sextants of the prostate. World J Urol 2014; 32: 925-930
• 71 Moore CM, Robertson NL, Arsanious N et al. Image-guided prostate biopsy using magnetic resonance imaging-derived targets: a systematic review. Eur Urol 2013; 63: 125-140
• 72 Hoeks CM, Schouten MG, Bomers JG et al. Three-Tesla magnetic resonance-guided prostate biopsy in men with increased prostate-specific antigen and repeated, negative, random, systematic, transrectal ultrasound biopsies: detection of clinically significant prostate cancers. EurUrol 2012; 62: 902-909
• 73 Puech P, Rouviere O, Renard-Penna R et al. Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsy--prospective multicenter study. Radiology 2013; 268: 461-469
• 74 Rosenkrantz AB, Kim S, Lim RP et al. Prostate cancer localization using multiparametric MR imaging: comparison of Prostate Imaging Reporting and Data System (PI-RADS) and Likert scales. Radiology 2013; 269: 482-492
• 75 Pokorny MR, de Rooij M, Duncan E et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. EurUrol 2014; 66: 22-29
• 76 Vargas HA, Akin O, Afaq A et al. Magnetic resonance imaging for predicting prostate biopsy findings in patients considered for active surveillance of clinically low risk prostate cancer. J Urol 2012; 188: 1732-1738
• 77 van den Bergh RC, Ahmed HU, Bangma CH et al. Novel tools to improve patient selection and monitoring on active surveillance for low-risk prostate cancer: a systematic review. EurUrol 2014; 65: 1023-1031
• 78 Thompson IM. Overdiagnosis and overtreatment of prostate cancer. Am Soc Clin Oncol Educ Book 2012; e35-e39