Prostate cancer screening Recent findings, management trends, solutions Vincent Fradet MD, FRCSC, PhD Associate Professor
Potential Conflicts of Interest Consultant, speaker or research agreement Abbvie Amgen Astra Zeneca Astellas Bayer Ferring Janssen None relates to Sanofi prostate cancer screening
Objectives Prostate cancer screening concepts Task force Controversy Future directions for screening
Screening objectives Randomised controlled trial = proof US Preventive Services Task Force, 2001
Prévalence peu élevée Stade préclinique «trop» décelable Limites effets délétères > avantages Tests trop peu sensibles (faux -) et spécifiques (faux +) Gains minuscules Tests non acceptables par la population cible Tests non acceptables pour la société US Preventive Services Task Force, 2001
Prostate cancer mortality is decreasing in Canada Dickinson et al. CMAJ Open 2016 epub
Prostate cancer mortality is decreasing in USA Siegel et al. CA Cancer J Clin 2016; 66:7
Prostate cancer is heterogeneous Esserman et al. JAMA 2009; 302:1685
Moyer et al. Ann Intern Med 157:120, 2012.
Canadian task force CTFPHC. CMAJ 2014; 186:1225
Province of Québec Collège des médecins du Québec, 2013
Quality of life effects of PSA screening Heijnsdijk et als, NEJM 2012
Simple schema for SDM Vickers et al. Ann Intern Med 2014; 161:441
PSA testing in the PLCO control arm Shoag et al. N Engl J Med 2016; 374:1795
Did the USPSTF assess harms fairly? Adequate evidence shows that up to 5 in 1000 men will die within 1 month of prostate cancer surgery and between 10 and 70 men will have serious complications but survive. Radiotherapy and surgery result in long term adverse effects, including urinary incontinence and erectile dysfunction in at least 200 to 300 of 1000 men treated with these therapies. Radiotherapy is also associated with bowel dysfunction Moyer et al. Ann Intern Med 157:120, 2012
Harms in the Göteborg study 14 years median follow-up Screening increased impotence by 120 / 10 000 invited men incontinence by 25 / 10 000 invited men Screening decreased prostate cancer death by 34 / 10 000 For each prostate cancer death averted, morbidity because of screen detected prostate cancer will render 4 more impotent men (120/34) <1 men incontinent (25/34) More primary endocrine Tx in control group (162 vs 80)
What seems to be missing from most of the PSA discussion is that the majority of men will have a normal PSA value and they will be reassured A normal PSA level offers peace of mind, a valued commodity in a world that is frequently full of troubling news. Detsky et al. JAMA 307:1035, 2012
Le médecin PROSTATE 2 % risk of prostate cancer metastasis or death 1 000 hommes AVEC dépistage 1 000 hommes SANS dépistage pendant 11 ans pendant 11 ans 167 hommes avec examens d'investigation 104 hommes avec 96 cancers examens d'investigation 60 cancers 33 surdiagnostics 4 décès 5 décès
SEIN 1 000 femmes avec dépistage 1 000 femmes sans dépistage pendant 20 ans pendant 20 ans 495 femmes avec examens d'investigation 325 femmes avec examens d'investigation 77 cancers 54 cancers 10 surdiagnostics 13 décès 20 décès
Lessons from mathematical modeling: Hamburg s Elbphilharmonie
What explains this curve? No treatment Treatment Treatment and screening ERSPC benefit Etzioni et al. Cancer 2012; 118:5955
Rise in metastatic disease will follow ~40,000 avoidable deaths in USA during 2013-2025 Gulati et al. Cancer 2014; 120:3519
USPSTF Recommendation does is matter? The AUA, EAU, ACS, ASIM, and NCCN all recommend some variation on shared decision making. Tasian et al. Urol Oncol 30:155, 2012
The Impact of the USPSTF Barocas et al. J Urol 194:1587, 2015
The real problems about prostate cancer screening using PSA Over- and under- screening Over- and under- treatment
What do PCPs do? Over and under screening Drazer et al. J Clin Oncol 2011; 29:1736
What do PCPs do? Over screening Walter et al. JAMA 2006; 296:2336
What do urologists do? Over and under treatment Cooperberg and Carroll. JAMA 2015 314:80
NOT to screen = savings??? Sipuleucel-t: $93,000 Abiraterone: $60,000 / yr Denosumab: $18,000 / yr Cabazitaxel: $80,000 Enzalutamide: $89,000 / yr (med 16 mos) Alpharadin: $69,000 for 6 injections US dollars
Prostate cancer screening The future of prostate cancer screening
The value of establishing an early baseline If PSA <1.0 at age 60, likelihood of prostate cancer death <0.3% 90% of prostate cancer deaths occurred in men with PSA >2.0 (top quartile) Vickers et al. BMJ 341:c4521, 2010 Vickers et al BMJ 346:f2023, 2013
Benefits and harms of PSA at age 60 Comparison of 2 populations: Malmö NOT screened Gothenburg screened For PSA >= 2 ng/ml, to prevent 1 prostate cancer death overall Excluding Dx <1yr Number needed to screen 23 16 Number needed to diagnose 6 3 Carlsson S. et als BMJ 2014
Another way to screen for PCa : STHLM3
Risk of cancer: All 36 % High-grade 13 %
Kallikreins (4k) in ProtecT
Clinical urility of 4k in ProtecT Cut-off of 6% risk high-grade Ca Avoid biopsy in 43% Detect 90% of high-grade Miss 14 high-grade 4 primary pattern 4
Conclusions Prostate cancer screening improves prostate cancer mortality Controversy highlights the importance of good screening practices Who? When? How? Patient s values matter in the balance Shared decision making Importance of avoiding over- and under- treatment Urologists play an important role in the screening balance Thank you!