Klinik und Poliklinik für Urologie und Kinderurologie Direktor: Prof. Dr. H. Riedmiller Prostate Cancer Who needs active surveillance? Klinische und molekulare Charakterisierung des Hoch-Risiko-Prostatakarzinoms. Martin Spahn
Epidemiologie 500.000 345.000 156.000 75.000 68.000? Bray et al. 2001 1995 1995 2006 2006 2050 2050 Ferlay et al. 2007 Eurostat 2006
Cancer Incidence Rates* for Men, US, 1975-2001 Rate Per 100,000 Prostate Colon & rectum Lung & bronchus Urinary bladder Non-Hodgkin lymphoma *Age-adjusted to the 2000 US standard population. Source: Surveillance, Epidemiology, and End Results Program, 1975-2001, Division of Cancer Control and Population Sciences, National Cancer Institute, 2004.
N Engl J Med 2009;360:1320-8. N Engl J Med 2009;360:1310-9. 20% No difference Reduction Of mortality PSA cut-off 4.0 ng/ml Sextant biopsies Pre-Screened short Follow up High contamination rate Only 40% biopsies
European Randomized Study of Screening for Prostate Cancer (ERSPC) Intention-to-screen analysis: To avoid one PCa death 1410 (95% CI, 1142-1721) men need to be screened 48 individuals need to be treated radically Overdetection and Overtreatment Schroeder et al. NEJM 2009
The diagnosis of low risk PCa is increasing Cooperberg et al, J Urol 2003
Rationale for active surveillance 1. Some men with PCa benefit from radical treatment 2. Treatment has adverse effects, and should be given only to those who stand to benefit 3. Most men with screen-detected PCa probably do not need treatment
Heidenreich et al., Eur Urol 2011 (59) 61-71
Inclusion criteria in Active Surveillance Series Author Publication year Inclusion criteria Treatment criteria Klotz 2006 PSA <15, Gleason <7, <T2b Soloway 2007 Age <80 years, PSA < 15, Gleason <6, < T2, <50% of two biopsy cores Carter 2007 PSA density <0.15ng/ml/cm 3, Gleason <6, <2 positive cores, <50% of any core involved Dall era 2008 PSA < 10, Gleason <6, <33% biopsy, T1/T2a Van As 2008 PSA < 15, Gleason <7, <50% positive biopsy cores (PBC), T1/T2a PSADT < 2 years, clinical progression, biopsy progression PSA progression, re-biopsy <7, stage progression, patient preference Gleason 4 or 5, >2 cores with cancer, >50% cancer in any core on re-biopy Increase in re-biopsy Gleason sum, PSA velocity >0.75ng/mL per year PSA velocity > 1ng/ml/yr, primary Gleason grade >/= 4, or PBC >50% on repeat biopsy Roemeling 2007 Screen detected As per clinician / patient decision
Results of Active Surveillance Author n Median age (years) Follow-up (Months) % remaining on surveillance Cancer specific mortality (%) Klotz 299 Not given 64 60 0.7 Soloway 99 66 46 92 0 Carter 407 66 34 59 0 Dall era 321 63 43 63 0 Van As 326 67 22 73 0 Roemeling 278 70 41 71 0
Active Surveillance with delayed treatment - Cancer specific survival - Klotz et al., J. Urol., 172:S48-S51, 2004
Active Surveillance ERSPC P = 0.689 Delayed RP Immediate RP Van den Bergh et al., Cancer 2010;116:1281 90
Natural course of Pca Albertsen tables N=767 Diagnosed 1971-1976 Clinical stage T2 Palliative treatment Dark grey = PCa Light grey = nonpca White = survival Albertsen et al., JAMA,1995 (8):626-631
Distribution Gleason Score 50% 40% Orginal Actual Percentag ge of Men 30% 20% 10% 0% 2 3 4 5 6 7 8 9 10 Gleason Score N = 1858 men Albertsen et al. J Natl Cancer Inst 97:1248-1253, 2005
Natural course of Pca N=14.516 Diagnosed 1992-2002 Clinical stage T2 Conservative treatment Dark grey = PCa Light grey = nonpca White = survival Lu-Yao et al., JAMA,2009 (11):1202-1209
Prostate cancer Median age at diagnosis: 68 yrs. 1 out of 4 PCa patients >75 yrs. 71% of all PCa deaths Ries L et al. SEER Cancer Statistics Review, 1975-2005.
Life Expectancy In 2002 Age Expected Lifetime (years) 60 19.7 65 15.9 70 12.6 75 9.6 Statistisches Bundesamt 2004
Prevalence of comorbidity across age groups Piccirillo et al. Critical Reviews Oncology-Hematology 2008;67(2):124-132
Estimates of Life Expectancy Walter et al. JAMA 2001; 285:2750-2756
Competing risk of mortality by age at diagnosis, cancer stage, grade, and comorbidity: cancer stage T2. Albertsen et al. JCO 2011;29:1335-1341
Natural history of prostate cancer Prostate cancer is inherently biologically heterogenous Patients have been staged differently in various studies Stage N 15 year PFS 15 year DSS % 95% CI % 95% CI T1-T2 300 48 37.3-58.7 80.9 73.6-88.2 T3-T4 183 46.6 32.7-60.5 56.5 44.6-68.4 M+ 159 6.2 0.8-10.6 5.7-0.1-11.5 Johansson et al., JAMA,1997;227:467-471
Who needs active surveillance? PSA <15, Gleason <7, <T2b Age <80 years, PSA < 15, Gleason <6, < T2, <50% of two biopsy cores PSA density <0.15ng/ml/cm3, Gleason <6, <2 positive cores, <50% of any core involved PSA < 10, Gleason <6, <33% biopsy, T1/T2a PSA < 15, Gleason <7, <50% positive biopsy cores (PBC), T1/T2a Screen detected
Who needs active surveillance? - Future aspects - Men with low risk PCa criteria Men with intermediate risk PCa and Charlson score >1 Men >75 yrs. of age Men ineligible for definitive local radical treatment