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A A cosacosa serve serve ilil PSA?PSA?

Clinica Clinica UrologicaUrologica, , UniversitUniversitàà VitaVita--Salute H San Raffaele, Salute H San Raffaele, Istituto Scientifico H San Raffaele, MilanoIstituto Scientifico H San Raffaele, Milano

Vincenzo Vincenzo ScattoniScattoni

A A cosacosa serve serve ilil PSA?PSA?1.1. Valutazione del paziente con BPHValutazione del paziente con BPH2.2. Diagnosi e Diagnosi e stadiazionestadiazione del tumore del tumore

prostaticoprostatico3.3. FollowFollow--upup dopo trattamentodopo trattamento

–– Diagnosi di recidivaDiagnosi di recidiva–– Valutazione Valutazione prognosticaprognostica




PSA: indicatore di volume prostaticoPSA: indicatore di volume prostatico

da Miano R, Tubaro A, Miano L in “PSA Antigene prostatico specifico”. CIC 2005

Indicatore di volume prostaticoIndicatore di volume prostatico

Previsione dellPrevisione dell’’incremento incremento volumetricovolumetrico

Roehrborn CG. J Urol 163 (1): 13-20, 2000

Previsione dellPrevisione dell’’incremento volumetricoincremento volumetrico

Roehrborn CG. J Urol 163 (1): 13-20, 2000

MTOPS: Rischio di progressione, RAU MTOPS: Rischio di progressione, RAU e chirurgia a 4 anni (placebo)e chirurgia a 4 anni (placebo)

J Urol 175:1422-1427, April 2006

Rischio di progressione

• TPV >= 31 ml

• PSA > 1.6 ng/ml

• Qmax < 10.6 ml(sec

• PVR > 39 ml

• Età > 62 anni

Marcatore per la strategia terapeuticaMarcatore per la strategia terapeutica

Bruskewitz R. Urology 54: 670-678, 1999

Marcatore per la strategia terapeuticaMarcatore per la strategia terapeutica

Roehrborn. Urology 53: 473- 480, 1999

PLESS: variazione dei sintomi e PLESS: variazione dei sintomi e QmaxQmax a 4 a 4 anni (placebo)anni (placebo)

PSA: marcatore dPSA: marcatore d’’organoorgano

ää Indicatore del volume prostaticoIndicatore del volume prostaticoää Indicatore dellIndicatore dell’’incremento del volume prostaticoincremento del volume prostaticoää Indicatore di rischio di progressione clinica, Indicatore di rischio di progressione clinica,

RAU e chirurgia RAU e chirurgia ääMarcatore di strategia terapeutica (Marcatore di strategia terapeutica (finasteridefinasteride))ää Indicatore per la variazione dei sintomi e Indicatore per la variazione dei sintomi e QmaxQmax

nei pazienti in terapia con nei pazienti in terapia con finasteridefinasteride




77--year risk of being diagnosed with year risk of being diagnosed with CaPCaP in a screening in a screening programmeprogramme

34

44

71

0

10

20

30

40

5060

70

80

3.0-6.0 6.0-10.0 >10

PSAAus G et al, Eur Urol 2004.

PSA: marcatore ideale??PSA: marcatore ideale??

N Engl J Med. 2004 May 27;350(22):2239-46.

Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter.

7%

10%

17%

24%27%

1% 1%2%

5%7%

0

5

10

15

20

25

30

?0-0.5 0.6-1.0 1.1-2.0 2.1-3.0 3.1-4.0

PSA Level (ng/ml)

% o

f M

en w

ith P

rost

ate

Can

cer

and

Hig

h-

Gra

de

Dis

ease

Percent with Prostate Cancer

Percent with Gleason > 7Disease

Thompson IM, et al. N Engl J Med. 2004 May 27;350(22):2239-46.

(13%) (10%)(12%)

(19%)(25%)

Relationship of the PSA Level to the Prevalence of Prostate CancRelationship of the PSA Level to the Prevalence of Prostate Cancer and Higher and High--Grade DiseaseGrade Disease

PSA: come migliorare lPSA: come migliorare l’’accuratezzaaccuratezza

DiagnosiDiagnosiääSensibilitSensibilitàà (PSA < 4.0 (PSA < 4.0 ngng/ml)/ml)ääSpecificitSpecificitàà (PSA 4.0(PSA 4.0--10.0 10.0 ngng/ml)/ml)

Improving sensibility Improving sensibility PSA< 4.0 PSA< 4.0 ngng/ml: Estimated risk/ml: Estimated risk

Thompson IM, et al. N Engl J Med. 2004

Gilbert et al

Urology 65: 549-553, 2005

AgeAge--related reference valuesrelated reference values

Conti G, Spatafora S in “PSA Antigene prostatico specifico”. CIC 2006

AgeAge--related reference valuesrelated reference values

Conti G, Spatafora S in “PSA Antigene prostatico specifico”. CIC 2006

%FPSA%FPSA

Scattoni V, Gion M in “PSA Antigene prostatico specifico”. CIC 2006

Stephan C et al. Cancer 104: 993-1003, 2005

PSA density PSA density

PSA PSA KineticsKinetics: : biologicbiologic approachapproach

–– PSA PSA velocityvelocity ((absoluteabsolute rate of rate of changechange of PSA of PSA over time)over time)•• 0.75 0.75 ngng/ml//ml/yearyear•• 2 2 ngng/ml//ml/yearyear

–– PSA PSA doublingdoubling time time (time (time requiredrequired toto doubledouble))•• 18 18 monthsmonths ((predictorpredictor of of outcomeoutcome))•• 1010--12 12 monthsmonths ((predictorpredictor of of outcomeoutcome))•• 10 10 monthsmonths ((predictorpredictor of of diseasedisease progressionprogression))

PSA PSA velocityvelocity in the in the diagnosisdiagnosis

Cut off 0.75 Cut off 0.75 ngng/ml//ml/yearyear

SensibilitySensibility SpecificitySpecificity

ääBLSABLSA 81%81% 50%50%ääERSPCERSPC 85%85% 18%18%

PSA PSA velocityvelocity in the in the diagnosisdiagnosis: limits: limits

ääBiologic variability in absence of disease Biologic variability in absence of disease has been estimated at 34%has been estimated at 34%ääAnalytical variation <20Analytical variation <20--46%46%ääA minimum of 3 measurements acquired A minimum of 3 measurements acquired

over a 1.5over a 1.5-- to 2 yrs interval to to 2 yrs interval to minimiseminimise the the effect of effect of ““normalnormal”” variationvariationääBest scenario: PSA < 4.0 Best scenario: PSA < 4.0 ngng/ml/ml

Boddy JL et al. BJU International 93: 735-738, 2004

(Complex)cPSA

(Free) fPSA15%

(inactive)iPSA40%

(BPH)BPSA27%

(proenzyme)proPSA

33%

ISOFORMS FREE PSA ISOFORMS FREE PSA

%proPSA%proPSA ([([––2]2]proPSAproPSA))


0

10

20

30

40

50

60

70

80

< 10% 10-20% 20-30% 30-40% 40-50% >50%

% pPSA

%

CancerPath. Gleason > 7

More Aggressive Cancers with Increasing % pPSA

Lein M et al. J Urol Deceber 2005

1. CPSA at at biopsy cutoff of 2.3 ng/ml offers the best specificity, PPV and screening efficacy among TPSA, FPSA, hK2 and calculated combinations

2. CPSA is table in storage at different temperature

3. Cost effective

4. Avoid contrived calculations

5. 19% of biopsies could be avoid compared with tPSA and DRE

Martin BJ et al. J Urol January 2006

PSA complessatoPSA complessatocPSAcPSA da solo > TPSA, ma = %FPSAda solo > TPSA, ma = %FPSA

%cPSA%cPSA = %FPSA= %FPSA

National Comprehensive Cancer Center Network (NCCN) GuidelinesäStart screening at 40 years

– If PSA ≤ 1.0 ng/ml- screen annually– If PSA ≤ 2.5 ng/ml, consider biopsy if

• PSA Velocity 0.2-0.5 ng/ml/year

– If PSA = 2.6-4 ng/ml, consider biopsy if• PSAD > 0.1 ng/ml/gr or • %FPSA < 10% or• PSA velocity > 0.75 ng/ml/year

National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology – v.1.2004, Prostate Cancer Early Detection

ääEAU guidelines (10/2006)EAU guidelines (10/2006)–– Positive DRE o PSA > 4.0 Positive DRE o PSA > 4.0 ngng/ml/ml–– PSA < 2.5PSA < 2.5--3 3 ngng/ml (recommendation grade C)/ml (recommendation grade C)

ääGuidelines of the Italian Group of prostatic Guidelines of the Italian Group of prostatic biopsiesbiopsies–– Same indications of EAU guidelines (2/2006)Same indications of EAU guidelines (2/2006)

Screening: ERSPCScreening: ERSPC

ääPSA < 1.0 PSA < 1.0 ngng/ml : non /ml : non èè necessario necessario rescreeningrescreening per 8 anniper 8 anniääPSA 1.0PSA 1.0--2.9 2.9 ngng/ml: migliorare la /ml: migliorare la

specificitspecificitàà e la selezione dei casi e la selezione dei casi potenzialmente aggressivi.potenzialmente aggressivi.ääPSA > 3.0 PSA > 3.0 ngng/ml: eseguire biopsia. /ml: eseguire biopsia.

Improving specificity: Improving specificity: PSA 4.0 PSA 4.0 ––10.0 10.0 ngng/ml/ml

Scattoni V et al. European Urology 36(6):621-30, 1999.

PSA and PSA and prostaticprostatic volume and volume and ageage

Miano R, Tubaro A, Miano L in “PSA Antigene prostatico specifico”. CIC 2006

Correlation in All Cancers (N=2044)Correlation in All Cancers (N=2044)

Prostate Prostate SizeSize

Cancer Cancer VolumeVolume

++++++

Prostate SizeProstate Size Cancer Cancer VolumeVolume

++++ --

-- ++++

---- ++ ++++

-- ++

- No Corr + <0.25 ++>0.25

<< 4040

4040--5555

>55>55

Prostate size Prostate size (gm(gm))

Cancer Volume Cancer Volume (cc)(cc) <<3 cc3 cc >3 cc>3 cc

11% 16%

18% 20%

17%17%

%FPSA>TPSA%FPSA>TPSA


Cancer risk according to %FPSACancer risk according to %FPSA


%FPSA%FPSAääCut off 25%Cut off 25%ää95% sensibility95% sensibilityää Increase 30% specificityIncrease 30% specificity

European Urology Supplements 2006

WhichWhich cutcut--off??off??


Variability of %FPSA: the Variability of %FPSA: the impact of prostatic volumeimpact of prostatic volume


Galosi AB, Montironi R in “PSA Antigene prostatico specifico”. CIC 2006

%FPSA and %FPSA and inflammationinflammation


HK2/FPSA= similar accuracyHK2/FPSA= similar accuracy


PSA e PSA e stadiazionestadiazione: : nomogramminomogrammi

Rocco F, Carmignani L, Bozzini G in “PSA Antigene prostatico specifico”. CIC 2005

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