PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age...

36
23.06.2016 | Axel Heidenreich PSA Screening and Diagnosis

Transcript of PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age...

Page 1: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

23.06.2016 | Axel Heidenreich

PSA Screening and Diagnosis

Page 2: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 2 23.06.2016 | Axel Heidenreich

The Problem……..

Seite 2RKI 2012

Page 3: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 3 23.06.2016 | Axel Heidenreich

The Problem……..

Seite 3RKI 2012

Page 4: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 4 23.06.2016 | Axel Heidenreich

Was sagen die Leitlinien?

Seite 4Heidenreich A et al., Eur Urol 2014; 65: 124 - 137

Page 5: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 5 23.06.2016 | Axel Heidenreich

• Dutch, retrospective, primary care database analysis; N: >60,000 PCa pts• Continuous increase of PSA testing incidence rate in men ≥45 yr:

– 2002: 15.5 per 1,000 person-yrs 2011: 54.3 per 1,000 person-yrs

– Higher increase in incidence rates as from 2005 than before 2005

• Estimation of relative risk on having a PSA test for men with different comorbidities:

Hamoen EHJ. Eur Urol Suppl 2013:12(1):e12(abs.12)

A rising incidence rate of PSA testing is seen from 2002 to 2011 despite recommendations to restrict PSA testing in several guidelines

PSA testing: discrepancies between guidelines and clinical practice

Data from poster

± 4-fold increase

Comorbidity Relative riskOverweight 1.50 (95% CI 1.39-1.62)

Psychiatric disease 1.31Joint disorders 1.30

Diabetes mellitus 1.29Respiratory disease 1.28

Cardiovascular diseases 1.27

What is the clinical reality?

Page 6: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 6 23.06.2016 | Axel Heidenreich

Screening: USA versus Europe

Seite 6

AUA Recommendation1 EAU Recommendation2

No PSA for men < 40 years Baseline PSA at age 40-45 years

No PSA for men 40-54 years

Shared decision and consent for men 55-69 years

Screening intervall ≥ 2 years adaptation of early detection dependen on 1rst PSA

No PSA for men > 70 years orr life expectancy < 15 years

PSA if life expectancy > 10 years

1Carter AB et al., J Urol 2013; 2Heidenreich A et al., Eur Urol 2013

Page 7: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 7 23.06.2016 | Axel HeidenreichSeite 7

1. Early detection of PCA reduces mortality2. Early detetion reduces frequency of locally advanced

and metastatic PCA3. Early detection in men > 10 years life expectancy4. Baseline PSA at age 405. Individualized, PSA adapted follow-up6. Risk models including biomarkers are mandatory for

the future

Page 8: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 8 23.06.2016 | Axel Heidenreich Schröder et al. N Engl J Med. 2009

Page 9: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 9 23.06.2016 | Axel Heidenreich Schröder et al. N Engl J Med. 2009

Page 10: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 10 23.06.2016 | Axel Heidenreich

Follow-up: 13 yearsRisk reduction 27%NO > 70 years

Page 11: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 11 23.06.2016 | Axel Heidenreich

Follow-up 9 years 11 years 13 years

numbers needed to invite 1410 979 781

numbers needed to detect 48 35 27

Screening only indicated if life expectancy > 10 yearsHigh Rate of overdiagnosis and overtreatment

Page 12: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 12 23.06.2016 | Axel Heidenreich

Göteborg randomised population-based PCA screening

• 32.298 men, 50-64 years• Biopsy at PSA > 3.4 ng/ml (1995 – 1998), PSA > 2.5

ng/ml since 1999

• PCA – incidence higher(12.7% vs 8.2%)• Rate of ≥ T3 or M1 significantly lower(p=0.0003)• Risk reduction PCA - death 44% (HR 0.56, 95% CI,

0.32-0.82, p = 0.002)

Hugosson J et al., Lancet Oncol 2010

Page 13: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 13 23.06.2016 | Axel HeidenreichHugosson et al. Lancet Oncology Juli 2010

Cumulative Cancer/Specific Mortality

Page 14: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 14 23.06.2016 | Axel Heidenreich

Göteborg screening trial

• 14 years follow up

• Risk Reduction of PCa mortality 0,56

• NNS (Number needed to be screened)

293

• NNT (Numbers needed to treat) 12

Hugosson et al. Lancet Oncology Juli 2010

Page 15: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 15 23.06.2016 | Axel Heidenreich

Early Detection reduces metastatic and locally advanced PCA

• Risk of metastases at initial diagnosis reduced by– 30% in ERSPC trial

– 48.9% in Göteborg study

• Risk of locally advanced PCA significantly (p < 0.001) reduced– cumulative incidence 0.67% versus 0.86%

– Risk reduction at 12 years 30%

Page 16: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 16 23.06.2016 | Axel HeidenreichEur Urol 2013; 64: 347 - 354

1. Early detection reduces PCA – related mortality2. Early detection reduces frequency of locally advanced

and metastatic PCA3. Early detection in men with life expectancy > 10

years4. Baseline PSA at age 40 years5. Individualized, PSA – adapted early detection6. Multivariable risk models for the furture

Page 17: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 17 23.06.2016 | Axel Heidenreich

Early detection of life expectancy > 10 years

• n = 1167 men, geb. 1921

• Blood samples 1981/1982 (60 years)

• Comparison with cancer registry 2006 (25 years Follow-up)

• Baseline < 2.0 ng/ml• significantly riské of diagnosis• significantly riské of metastases

Page 18: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 18 23.06.2016 | Axel Heidenreich

• Baseline < 2.0 ng/ml• risk of death 26timesÝ

if PSA > 2.0 ng/ml

Ø 62% of all PCAØ 80% of all metastasesØ 90% of all death

Early detection of life expectancy > 10 years

• n = 1167 men, geb. 1921

• Blood samples 1981/1982 (60 years)

• Comparison with cancer registry 2006 (25 years Follow-up)

Page 19: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 19 23.06.2016 | Axel HeidenreichEur Urol 2013; 64: 347 - 354

1. Early detection reduces PCA – related mortality2. Early detection reduces frequency of locally advanced

and metastatic PCA3. Early detection in men with life expectancy > 10 years4. Baseline PSA at age 40 years5. Individualized, PSA – adapted early detection6. Multivariable risk models for the furture

Page 20: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 20 23.06.2016 | Axel Heidenreich

Baseline PSA at Age 40

• median PSA in men 30-49 years 0.6 – 0.78 ng/ml

• Loeb et al. (Urology 2006)

– N = 13.943 men < 60 Jahre

– PSA > 1.0 ng/ml => 14.6times elevated risk PCA (41-49J)

=> 7.6times elevated risk PCA (51-59 J)

=> significantly more T3, N1 & M1

Page 21: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 21 23.06.2016 | Axel Heidenreich

• median PSA in men 30-49 years 0.6 – 0.78 ng/ml

• Västerbotten Intervention Project (BMJ 2009)– Risk of PCA after a mean follow-up of 23 years

• 3.9% PSA < 1.0 ng/ml (reference group)

• OR 9.1Ý PSA 1.0 – 2.0 ng/ml

• OR 23.3Ý PSA 2.0 – 3.0 ng/ml

• OR 43.9Ý PSA 3.0 – 4.0 ng/ml

Baseline PSA at Age 40

Page 22: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 22 23.06.2016 | Axel Heidenreich

• median PSA in men 30-49 years 0.6 – 0.78 ng/ml

• Malmö Preventive Project (BMJ 2013)– Baseline-PSA correlates with metastases and PCA-related

mortality • Metastases after15 years elevated 3times (45-49J)

• Metastases after 15 years elevated 10times (50-55J)

• PCA-related death after 15 years elevated 2.7times (45-49J)

• PCA-related death after 15 years elevated 5.1times (50-55J)

Baseline PSA at Age 40

Page 23: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 23 23.06.2016 | Axel HeidenreichEur Urol 2013; 64: 347 - 354

1. Early detection reduces PCA – related mortality2. Early detection reduces frequency of locally advanced

and metastatic PCA3. Early detection in men with life expectancy > 10 years4. Baseline PSA at age 40 years5. Individualized, PSA – adapted early detection6. Multivariable risk models for the furture

Page 24: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 24 23.06.2016 | Axel Heidenreich

Risk Adapted Early Detection

• Screening intervalls

– 2-4 years if PSA > 1.0 ng/ml at age 45 – 49 years

– Up to 8 years if PSA < 1.0 ng/ml

Page 25: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Intervall Cancers

Schröder Ito Hugoson Candas

PSA, initial ≤ 1.0 ng/ml ≤ 1.0 ng/ml ≤ 3.0 ng/ml ≤ 3.0 ng/ml

N 1703 4794 5267 5387

Follow-up 4, 8 years annually 2, 4 years anually

PCA 8 (0.4%) 4 (0.1%) 111 (2.1%)* 134 (2.5%)*

Recommendation 8 years 4-5 years 4 years 7 years

* 3 (0.04%) if initial PSA < 1.5 ng/ml0, if initial PSA < 1.0 ng/ml

Page 26: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 26 23.06.2016 | Axel Heidenreich

Diagnosis

• Diagnosis of Prostate Cancer needs histopathological validation despite modern imaging studies

• Prostate Biopsy:

• guideline recommendation: TRUS – guided 10 - 12-core Biopsy

è TRUS-guided, transrectalè TRUS-guided, transperinealè MRI – TP – Fusion Biopsy

Page 27: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 27 23.06.2016 | Axel HeidenreichSeite 27

Risk Calculators

Vergleich der Risikokalkulatoren und PSA, PSA Quotient

0 20 40 60 80 1000

20

40

60

80

100

100-Spezifität

Sen

sitiv

ität

ERSPC-3ERSPC-4PCPTSRCPSA bei BiopsiePSA Quotient

Risk Calculators topredict a positive biopsyand the presence of high risk PCA

Page 28: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 28 23.06.2016 | Axel Heidenreich

PCA – primary diagnosis

17

8

9

10

11

2

3

4

5

12 6

• Low detection rate 30-35%• Overdiagnosis• Complications & infection 5-8%• Urosepsis 0.5 – 3%

Page 29: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

» N=7,216 men who underwent initial prostate biopsy (Bx) (1993-2011)

Multivariate analysis: positive predictor – negative predictor

Van Den Heuvel S. Eur Urol Suppl 2012:11(1):abs.825

These data are useful to counsel pts prior to initial Bx on the complication risk

Complications of initial prostate biopsy and predictors for complications: results from ERSPC Rotterdam

Complication N (% of pts) Independent predictors OR 95% CI PHaematospermia 3,545 (54.7%) Age (continuous) 0.91 0.90-0.92 <0.001

Year (>2001 vs ≤2001) 1.25 1.11-1.40 <0.001Comorbidities (yes vs no) 0.82 0.74-0.91 <0.001

Prostate volume (continuous) 0.99 0.99-0.99 0.046Haematuria 1,577 (25.0%) Comorbidities (yes vs no) 1.2 1.1-1.3 0.005

Prostate volume (continuous) 1.01 1.01-1.01 <0.001Pain 306 (5.0%) Age (continuous) 0.97 0.95-0.99 0.02

Year (>2001 vs ≤2001) 0.66 0.49-0.88 0.005Fever 261 (4.2%) No significant predictors

Hospitalisation 44 (0.7%) No significant predictors

Page 30: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Complications of Biopsy Techniques

Complications Transrectal1 Transperineal2

Pain at Biopsy 43,6% 0%UTI & fever 17,5% 0%Prostatitis 4.5% 0.4%Urosepsis 0.7% 0%Hematuria 65,8% 41,8%Hemospermia 92,6% N/AHematochezia 36,8% 0%Acute urinary retention n.k. 13,4%

1 DJ. Rosario et al.BMJ 2012;344 2 own data

Page 31: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Biopsy PCA-Detection Rates

PCA-DetectionTRUS – guided biopsy1 30% – 43%

Transperineal Biopsy 62.5%

MRT-Fusion Biopsy(biopsienaiv)3 66%

1 EAU Guidelines on PCA2 own data3 CM. Moore et al. Eur Urol 63 (2013), 125-140

Page 32: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Dorsal: 76%

Anterioventral: 83,3%

Transitional: 55,5%

Perineal Prostate Biopsy

Page 33: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Perineale Prostatabiopsie –eigene Erfahrungen

Einteilung nach Gleason Score:Gleason 6 37,5% Gleason 7 25% Gleason 8-10 37,5%

Page 34: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

mpMRT

Figure 3 shows the basal sectors that were added to thebiopsy plan when prostate volume was greater than 50 cc.Automatic needle placement for systematic cores was notavailable at that time. The median number of targetedcores was 4. Depending on lesion size, 2 to 6 targeted coreswere taken.

In the first 10 men the whole procedure, includingplanning and navigation, took around 60 minutes. Laterthe intervention time decreased to 30 minutes per patient,including larynx mask anesthesia. General anesthesia

helps minimize motion artifact and is the most appreci-ated biopsy analgesia for German men.12 Antibiotic pro-phylaxis consisted of fluoroquinolone treatment for3 days.

A 20-item purposely designed questionnaire was sentto all patients to document post-biopsy morbidity (erectilefunction, infections complications, hematuria and hema-toma) and disease specific followup (PSA, further prostatebiopsies, actual treatment regimen and, if available, his-topathology reports).

Statistical analysis was performed using SPSS!,version 20 with p <0.05 considered statistically signifi-cant. We calculated k to compare targeted vs systematicapproaches. PC risk groups were defined according toNCCN guidelines.13 PSA cutoffs and biopsy criteria wereused. Low risk and very low risk were combined into asingle risk level, including lowdGleason score 2 to 6 andPSA less than 10 ng/ml, intermediatedGleason score 7 orPSA 10 to 20 ng/ml and highdGleason score 8-10 or PSAgreater than 20 ng/ml.

RESULTSIn 200 of 347 patients (58%) with suspicion of PCbiopsy samples revealed PC (table 1). In 147 of the200 men (73.5%) biopsy proven PC was intermedi-ate or high risk according to NCCN criteria.13 Of177 men undergoing primary biopsy cancer wasdiagnosed in 114 (64%), including low risk tumors in23 (20%). Of 170 patients without a previous cancerdiagnosis re-biopsy was positive in 86 (51%),revealing clinically relevant tumors in 56 (65%). Atotal of 100 patients had 1 previous negative biopsyand 70 had 2 or more previously negative trans-rectal biopsies (detection rate 51 of 100 or 51% and35 of 70 or 50%, respectively).

On multiparametric 3 Tesla MRI without anendorectal coil 104, 149 and 94 cases were diag-nosed as highly, questionably and not suspicious forPC, respectively. We did not use the Prostate Im-aging Reporting and Data System (PI-RADS) scoredescribed in the 2012 European Society of Urogen-ital Radiology (ESUR) guidelines14 because thepublication was not available when the study pro-tocol was initiated. Of 104 men with MRI lesionsconsidered highly suspicious tumor was detected in86 (82.6%), including 62 with a Gleason score of 7 orgreater. In 149 patients with questionable MRIlesions tumor was detected in 100 (67%). Of 94 cases80 (85.1%) described as not suspicious for PC onMRI were also negative on biopsy.

Table 2 shows a detailed evaluation of targetedvs template biopsies. Biopsies from 1 trajectory wereonly taken once. If this trajectory was located in asuspicious area, it was considered targeted andsystematic since no additional systematic biopsieswere taken from this region. Moreover, routinehistopathological evaluation at our center did not

Figure 2. Three Tesla mp-MRI without endorectal coil ques-tionably suspicious for PC. T2 images with diffuse low intensesignal in peripheral zone (A), type 2 enhancement curve (C ) anddecreased ADC (D) without correlate in high b values (B).

Figure 1. Three Tesla mp-MRI without endorectal coil highlysuspicious for PC. T2 image with homogeneous low signalarea (A), focal area with hyperintense signal on long b800b-value images (B), type 3 contrast enhancement curve intypical localization (C ) and focal area with decreased ADC (D).

1382 MAGNETIC RESONANCE IMAGING TARGETED BIOPSY FOR DETECTION OF PROSTATE CANCER

Page 35: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

How to Perform Image-guided Prostate Biopsy: In-bore and Fusion 3 Approaches.Kuru T, Herden J, Zugor V, Akbarov I, Pfister D, Porres D, Heidenreich AEur Urol Focus 2016; article in press

MRI – TRUS Fusion – 4 Steps1. mpMRI done, suspicious areas identified and marked

=> ESUR score

MRI – TRUS Fusion – 4 Schritte1. mpMRI done, suspicious areas identified and marked

=> ESUR score2. Surface reconstruction in MRI, caculation prostate

volume

MRI – TRUS Fusion – 4 Schritte1. mpMRI done, suspicious areas identified and marked

=> ESUR score2. Surface reconstruction in MRI, caculation prostate

volume3. Reconstruction of prostatic area via 3D-TRUS

MRI – TRUS Fusion – 4 Schritte1. mpMRI done, suspicious areas identified and marked

=> ESUR score2. Surface reconstruction in MRI, caculation prostate

volume3. Reconstruction of prostatic area via 3D-TRUS4. Elastic surface reconstruction, marking of the MRI –

suspicious areas

Page 36: PSA Screening and Diagnosis - oncologypro.esmo.org · No PSA for men < 40 years Baseline PSA at age 40-45 years No PSA for men 40-54 years Shared decision and consent for men 55-69

Seite 36 23.06.2016 | Axel Heidenreich

mpMRI of the Prostate

Heidenreich A et al., Eur Urol 2014; 65: 467-479

Indication

§ Re-Biopsie following negative 1rst-line

Bx

§ identification of PCA in the anterior zone

(TP - biopsy)

§ local staging in selected cases with

intermediate/high risk PCA