Prostate cancer screening Recent findings, management trends, solutions

Transcription

1 Prostate cancer screening Recent findings, management trends, solutions Vincent Fradet MD, FRCSC, PhD Associate Professor

2 Potential Conflicts of Interest Consultant, speaker or research agreement Abbvie Amgen Astra Zeneca Astellas Bayer Ferring Janssen None relates to Sanofi prostate cancer screening

3 Objectives Prostate cancer screening concepts Task force Controversy Future directions for screening

4 Screening objectives Randomised controlled trial = proof US Preventive Services Task Force, 2001

5 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

6 Prostate cancer mortality is decreasing in Canada Dickinson et al. CMAJ Open 2016 epub

7 Prostate cancer mortality is decreasing in USA Siegel et al. CA Cancer J Clin 2016; 66:7

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9 Prostate cancer is heterogeneous Esserman et al. JAMA 2009; 302:1685

10 Moyer et al. Ann Intern Med 157:120, 2012.

11 Canadian task force CTFPHC. CMAJ 2014; 186:1225

12 Province of Québec Collège des médecins du Québec, 2013

13 Quality of life effects of PSA screening Heijnsdijk et als, NEJM 2012

14 Simple schema for SDM Vickers et al. Ann Intern Med 2014; 161:441

15 PSA testing in the PLCO control arm Shoag et al. N Engl J Med 2016; 374:1795

16 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

17 Harms in the Göteborg study 14 years median follow-up Screening increased impotence by 120 / invited men incontinence by 25 / invited men Screening decreased prostate cancer death by 34 / 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)

18 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

19 Le médecin PROSTATE 2 % risk of prostate cancer metastasis or death hommes AVEC dépistage 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

20 SEIN femmes avec dépistage 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

21 Lessons from mathematical modeling: Hamburg s Elbphilharmonie

22 What explains this curve? No treatment Treatment Treatment and screening ERSPC benefit Etzioni et al. Cancer 2012; 118:5955

23 Rise in metastatic disease will follow ~40,000 avoidable deaths in USA during Gulati et al. Cancer 2014; 120:3519

24 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

25 The Impact of the USPSTF Barocas et al. J Urol 194:1587, 2015

26 The real problems about prostate cancer screening using PSA Over- and under- screening Over- and under- treatment

27 What do PCPs do? Over and under screening Drazer et al. J Clin Oncol 2011; 29:1736

28 What do PCPs do? Over screening Walter et al. JAMA 2006; 296:2336

29 What do urologists do? Over and under treatment Cooperberg and Carroll. JAMA :80

30 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

31 Prostate cancer screening The future of prostate cancer screening

32 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

33 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 Number needed to diagnose 6 3 Carlsson S. et als BMJ 2014

34 Another way to screen for PCa : STHLM3

35

36 Risk of cancer: All 36 % High-grade 13 %

37 Kallikreins (4k) in ProtecT

38 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

39 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!