NY Prostate Cancer Conference - C. Bangma - Session 3: Predicting indolent and low risk prostate cancerPresentation Transcript
Predicting indolent and low risk prostate cancer Chris Bangma New York, april 2011
Retrospective findings in screen-detected ‘PRIAS-suitable’ PCa (n = 616) (Van den Bergh et al, Eur Urol,2009) Many cases of prostate cancer are not lethal if left untreated
What is that: ‘indolent’ ?
What the patient wants: no symptoms during life
What the scientist wants: a molecular pattern
What the clinician wants: a recognisable phenomenon
Preparing the stage for indolent low risk thinking Pivotal papers 1: Epstein 1993 < 0.15 ng/ml/ml PSAD < 50 % per core Cancer < 3 Number pos biopsy cores < 10 ng/ml PSA < 7 < 7 Gleason sum < 0.5 ml Tumour Volume In pretreatment after biopsies In radical prostatectomy specimen
Preparing the stage for indolent low risk thinking Pivotal papers 2: Kabalin 1989
Unsuspected Pca in 66 cystoprostatectomy specimens
38 % Pca, mean volume 1.1 ml (half of these < 0.01 ml)
Preparing the stage for indolent low risk thinking Pivotal papers 3: d’Amico 2001
Mortality related to pretreatment parameters
1800 men, 44 institutes
‘… the pretreatment risk groups in this study are only applicable to patients with clinically localized prostate cancer undergoing RP or RT therapy….’
Predicting indolence once there is cancer: making a nomogram Clinical diagnosis (at time of tumor diagnosis) PSA < 15 PSAD < 0.2 Pos cores <3 Pathological diagnosis: One focus < 5 mm Pca Biological diagnosis: No progression during lifetime, PSADT > 10 years 1 2 3 4 1+2+3+4 = indolent disease Focal Insignificant Minimal Pathologic diagnosis Biological diagnosis clinical diagnosis
Incidence of histologic indolent disease in clinical series and in the general population Indolent = PSA< 10ng/ml, tumour volume < 0.5 ml, Gleason < 7 10 48 6 20 10 Percentage of indolent disease screening screening clinical clinical clinical Origin 2196 247 1254 409 222 Number of patients with Radical Prostatectomy Catalona J.Urol. 2006 Steyerberg J.Urol. 2007 Huland Eur.Urol. 2003 Kattan J.Urol. 2003 Noguchi J.Urol. 2001 series
Indolence versus low risk: is there a difference? NCCN guidelines 2010 or and 8-10 > 20 3a High risk 7 10-20 2b-2c Intermediate risk 2-6 < 10 1-2a Low risk < 3 cores pos < 50 % ca PSAD< 0.15 < 6 < 10 1 Very low risk other Gleason PSA T-stage
Which nomograms do we have predicting indolence? 0.73 0.77 0.65-0.79 Discriminative ability (AUC) 1 pos core only Early hormones Specific parameters + -- + + + + + - + + + + + + - + + + + - PSA Gleason Volume Biopsy detail Age - + + - General population Nakanishi Cancer 2007 Kattan, Cancer 2008 Steyerberg, J.Urol. 2007 Kattan, J.Urol 2007
Man 60 years old, PSA 4,0 ng/ml, gland volume 40 ml, DRE = T1c, 1 pos biopsy with 5 mm cancer and 120 mm benign tissue, no endocrine therapy 32 % 92 % (10 years DSS) 65 % (+/- 5) 22 % (23 % in revised nomogram) Indolent disease Nakanishi Cancer 2007 Kattan Cancer 2008 Steyerberg J.Urol. 2007 Kattan J.Urol. 2003
Predicting a positive biopsy and predicting indolence go hand in hand…
A risk based strategy improves PSA driven detection of prostate cancer, Roobol, Vickers, et al, 2010
DRE, PSA, TRUS Volume
Performing biopsy at 12.5 % risk or more reduces 33 % of number of biopsies, missing 13 % of (predominantly indolent) tumours
The Prostate Cancer Prevention Trial and European Randomized Study of Screening for Prostate Cancer risk calculators indicating a positive prostate biopsy: a comparison. Van den Bergh et al , 2008
How to use nomograms
‘… Clearly, no risk instrument should be used in isolation to direct patients towards or away from treatment alternatives…’ Cooperberg, Cancer 2008
Factors not measured by current models: baseline quality of life, comorbidity , life expectancy, treatment preference
Albertsen P C et al. JCO 2011;29:1335-1341
Who do we need to treat?
Tumour biology versus host biology
Tumour lead time 8-13 years
Patient with life expectancy of >10 years
Is a nomogram being used?
Beyond the technical evaluation: the practical evaluation:
When will a patient allow for accepting calculator based recommendations? And when does he refuse?
Compliance with biopsy recommendations by a prostate cancer risk calculator. Van Vugt et al abstract, 2011 EAU
Both urologists and patients were compliant in 245/291 cases (84%).
38 of the 119 (31%) were non-compliant with ‘no biopsy’ recommendations.
Urologists reason for non-compliance was an elevated PSA (≥3ng/ml, 87% = 33/38)
Riskindicator # 6 calculating individual probability on indolent Pca based on population data Simplicity: www.uroweb.org
Compliance to therapy advise in low risk Van Vugt 2011
Prospective analysis of Risk Calculator in 5 Dutch hospitals
Inclusion criteria: clinical stage T1c, T2a-c, PSA < 20ng/ml, <50% positive sextant biopsy cores, ≤20 mm cancer, ≥ 40 mm benign tissue, Gleason ≤ 3 + 3, no urological symptoms (except for urinary symptoms)
213 low risk
50 potentialy indolent on Risk Calculator (> 70 %)
163 advised active treatment, 50 Active Surveillance
Most patients (42/50, 84%) compliant with an AS recommendation.
49 choose AS in contrast to AT recommendations (49/163, 30%)
Improving nomograms for individualised risk assessment