Can we detect prostate cancer in a new way? - Dagens · PDF fileCan we detect prostate cancer...

Can we detect prostate cancer in a new way?

Urologisk kreft Radiumhospitalet, Oslo, March 31st, 2016

Tobias Nordström M.D. Ph.D. Danderyds Hospital Dpt Medical Epidemiology and Biostatistics, Karolinska Institutet

Tobias Nordström, MEB Karolinska Institutet

Outline

Testing for prostate cancer is common, unstructured and unequal The STHLM3 study – published and unpublished results Next steps – a new diagnostic chain

2 Tobias Nordström, MEB Karolinska Institutet

Data from The Stockholm PSA and Biopsy Registry shows a de-facto, unstructured, screening with PSA in Stockholm

130,000 PSA tests and 5,000 biopsies taken yearly

2,000 prostate cancers/year

65% of all men aged 50-69 has taken at least one PSA-test in the last 5 years

Stockholm PSA and Biopsy Registry Data from 450,000 men All testing in Stockholm since 2003 Complete records •  All PSA-test •  All biopsy/pathology

results •  Detailed information

on all cancers

Ref: “Prostate-specific Antigen (PSA) Testing Is Prevalent and Increasing in Stockholm County, Sweden”, European Urology 2013 3 Tobias Nordström, MEB Karolinska Institutet

But today’s unstructured screening with PSA in Stockholm is not optimal

38% of men with PSA < 1 takes a new test in 2.5 years

60% of all men biopsies are negative

50% of all cancers diagnosed are Gleason 6

Source: Stockholm PSA and Biopsy Registry 4 Tobias Nordström, MEB Karolinska Institutet

Today’s screening with PSA is unequal

Share that had a PSA taken (10 years) Share with increased PSA (4-10 ng/ml) followed-up with biopsy within 12 months

Lower educational level

[≤ 9 years]

54%

27%

Higher educational level

[≥ 13 years]

61%

40%

Ref: “A population-based study on the association between educational length, prostate-specific antigen testing and use of prostate biopsies“, Scand J Urology 2015


The Challenge

Develop a better prostate cancer test than PSA Create structure for prostate cancer testing


STHLM3 is collaboration between Stockholm County Council and Karolinska Institutet to develop a better prostate cancer test

•  Develop a new prostate cancer test that can replace PSA

•  Identify at least as many aggressive

cancers as PSA •  Significantly reduce number of

biopsies •  Demonstrate good health economy •  Combine many existing markers

Objective Conditions Method

STHLM3


We have followed a structured process to identify the best markers for the STHLM3 Test

Literature screening of 1,000+ potential plasma and genetic markers

150+ plasma markers evaluated 2011-2012

STHLM3 Test calibrated Collection on PSA 1-3 data Test of logistics 2012

Step 1 Literature Search

Step 2 STHLM2 Cohort [26,000 men]

Step 3 STHLM3 Training [11,130 men]

Step 4 STHLM3 Validation [47,688 men]

Prospective evaluation of STHLM3 Test 2013-2014


STHLM3 combines biomarkers and clinical data into the STHLM3 Test

•  Total PSA •  Free PSA •  Intact PSA •  hK2 •  MSMB •  MIC-1

•  Protein markers

• Genetic markers

• Clinical data

STHLM3 Test

= f

Risk factors •  Age •  Family history •  Previous biopsy

* Only measured on biopsied men

Prostate Exam •  Prostate volume* • DRE*


STHLM3 in numbers

145,905 men in Stockholm invited

58,818 men recruited 6,777 men biopsied


We have conducted three major analyses

Implement population based screening with the STHLM3 Test What would be the effects of population based screening with the STHLM3 Test? Replace clinical practice using PSA with the STHLM3 Test What would be the effects of replacing current clinical practice with the the STHLM3 Test with equal sensitivity to find aggressive prostate cancer as today? Health Economy What does the STHLM3 Test mean from a health economy perspective?

1

2

3


Population based screening with the STHLM3 Test


In population based screening the STHLM3 Test reduces biopsies with 32% with equal number of aggressive cancers

STHLM3 in population based screening versus PSA≥3

32% less biopsies

Equal number of GS7+

17% less GS6

44% less biopsies in men without cancer

Ref: ”STHLM3: A prospective population-based diagnostic study for prostate cancer screening in men 50-69 years”, Lancet Oncology, 2015 14 Tobias Nordström, MEB Karolinska Institutet

All markers have significant value for the result

Ref: ”STHLM3: A prospective population-based diagnostic study for prostate cancer screening in men 50-69 years”, Lancet Oncology, 2015

Marker Total PSA Age Family history Previous biopsies Genetic score

MSMB MIC1 Free PSA Intact PSA HK2 DRE

Prostate volume

Multivariate P-value

0.008

<0.001 0.004

<0.001

0.006 <0.001 0.047

<0.001 <0.001 <0.001

<0.001 <0.001

Risk factors Biomarkers

Prostate exam

Univariate P-value

<0.001

<0.001 0.005

<0.001

<0.001 <0.001 <0.001 <0.001 0.194

<0.001

<0.001 <0.001


The STHLM3 test identifies more GS7+ versus PSA

PSA 1 - 2 PSA 2 - 3 PSA 3 - 4 PSA 4 - 5 PSA 5 - 10

9%

23%

22%

25%

25%

12%

15%

19%

PSA STHLM3 Test

0%

0%

Share Gleason 7+ for PSA and STHLM3 in different PSA intervalls


The STHLM3 test gives a reduction in small GS6 cancers

Selected by PSA

Selected by STHLM3 Model

0-10 mm

Gleason Score 3+3

> 10 mm 0-10 mm

Gleason Score 3+4

> 10 mm 0-10 mm

Gleason Score 4+3

> 10 mm 0-10 mm

Gleason Score ≥4+4

> 10 mm

700

600

500

400

200

100

761

608

106 114

180 190

212 217

49 45

76 76

35 28

51 47

Number of cancers 95% confidence interval

800

Significant reduction of small Gleason 6 tumors


The STHLM3 Test works equally well in different age strata

Age 50-54 55-59 60-64 65-69 50-69

Participants

10,276

10,827

11,029

15,478

47,610

Biopsies 466 840 1337 2,304 4,947

Biopsy outcome

Benign 292 (62%) 547 (65%) 845 (63%) 1397 (61%) 3,081

Gleason Score 6

111 (24%) 201 (24%) 295 (22%) 521 (23%) 1,128

Gleason Score ≥7

63 (14%) 92 (11%) 197 (15%) 386 (17%) 738

Saved biopsies

All 35% 41% 30% 34% 32%

Gleason Score 6

30% 26% 16% 16% 17%

Benign 45% 53% 41% 50% 44%


Replace Current Clinical Practice with the STHLM3 Test

Total PSA, Free PSA, Family history, Age, Earlier prostate biopsies, Prostate volume, DRE


Next steps

Evaluate STHLM3 in clinical practice in primary health care in Stockholm Evaluate STHLM3 in combination with MRI and guided biopsies


Acknowledgements

STHLM3 Core

STHLM3 Scientific Advisory Board Pathology Urology KI Biobank

Henrik Grönberg Martin Eklund Markus Aly Jan Adolfsson Freddie Hamdy Ken Muir Lars Egevad Olof Jansson Magnus Törnblom Christer Kihlfors Lars Häggarth Ulf Leander Lennart Wagrell Anders Hallin Mark Divers James Thompson Anki Carman Amina Said

Funding Mark Clememets Johan Lindberg Astrid Björklund Jan-Erik Damper Jonas Hugosson Anders Bjartell Caroline Elmér Bo Jacobsson Mikael Lagerqvist Lundholm C-G Nettelbladt Renström Peter Arnelöv Cecilia Agarth Carita Björkman

Tobias Nordström Carin Cavalli-Björkman Britt-Marie Hune Peter Wikund Peter Albertsen Ian Thompson Håkan Ageheim Magnus Annerstedt Linnea Ekström Ehn Andreas Thorstenson Dushanka Kristiansson Daniel Altman Ulf Bergerheim Tove Rylander Rudqvist Rafat Samara Staffan Bergh Emma Ridell 22

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