Krzysztof Szkarłat Surveillance: Where Are We? Department of Urology and Urological Oncology Multidisciplinary Hospital Koscierzyna Poland
Epidemiology PC is the most common cancer among man PC is the second cause of death of cancer among man
Medical malpractice When doctor is not treating and he should When doctor is treating and he should not When doctor is treating but not in a way he should
Personalized medicine
The Worldwide Epidemiology of Prostate Cancer: Perspectives from Autopsy Studies G.P. Haas at all. Can J Urol. 2008 Age US White 3 US Black 3 Japan19 Spain 28 Greece 29 Hungary 30 21-30 8 8 0 4 0 0 31-40 31 31 20 9 0 27 41-50 37 43 13 14 3 20 51-60 44 46 22 24 5 28 61-70 65 70 35 32 14 44 71-80 83 81 41 33 31 58 81-90 48 40 73
Guidelines on Primary Treatment of PC
AS what s new? Recognition and evidence of overtreatment Definition of clinically insignificant disease Better understending of PSA kinetics MRI more widely use PCA3, LHK4 and other biomarkers? New studies Longer follow up of surveillace cohorts, QOL data Doubts if Gleason 6 is real cancer (lethal disease)
Strong consideration should be given to renaming low grade PC with a less anxiety producing diagnosis December 5 7, 2011 Bethesda, Maryland
Predicting 15-year prostate cancer specific mortality after radical prostatectomy. Eggner S, Scardino P, Walsh P at all. J Urol.2011 23 910 Radical Prostatectomies 12 000 Gleason 6 or less Risk of PC death after RP in men 60-69 0,2% after 20 years (although significant PSA failure rate) Is Gleason pattern 3 a real cancer?
Primary tumor explants in nude mice (N. Maitland) Gleason 7 and more 60% take rate Gleason 6 and less 0% take rate
Active Surveillance v. Watchful Waiting
AS inclusion criteria
For Which Older Man is AS a Safe Management Option Low risk (d Amico) Stage T1c/T2a Very low risk (Epstain) Stage T1c PSA<10 ng/ll Gleason score 6 or less PSAD <0,15 Gleason score 6 or less Favorable Risk < 3 cores with cancer < 50% cores involvement
How to do it? What kind of follow up? Group PSA DRE Biopsy Other Toronto Klotz Canary PASS Multicenter Q 3 mo for 2 years than Q 6 mo Q 6 mo for 2 years than Q 6-12 mo At 9-12 mo than Q 3-5 y to age 80 y Q 6 mo Q 6-12 mo At 18 mo than 1-3 y MRI if PSAD < 3 y or increase in volume or Gleason 3+4 Hopkins Carter, Epstain Q 6 mo Q 6 mo Q 1 y to age 75 y 20 biopsies!!!!!
Results of active surveillance
When to stop AS and start Active Treatment? Klotz 2010 Carter 2007 Van As 2007 Van den Bergh 2010 Solovay 2010 Dall-Era 2008 PSA DT < 3 yrs < 3 yrs PSA Velocity <1 ng/ml/ yr <0,75 ng/ ml/yr Grade Progression Gl 4+3 Gl 7 or > 2 cores or >50% core 4+3 or > 50% core Gl 7 or > 2 cores Gl 7 or > 2 cores Gl 7 or > Clinical Progression 50% Increase In mass > T2
June 2015 26AS cohorts involving 7627 men Overal radical treatment rate 8,8% per yer Approximately 30% in 4 yeras Rate varied 20 fold!! From 1,1% per year to 22,2% per year
Prostate-specific antigen kinetics during follow-up are an unreliable trigger for intervention in a prostate cancer surveillance program. Ross AE at all, JCO 2010 290 man on AS (Epstain Criteria) 35% developed pathological progression PSA kinetics not predictive of adeverse biopsy findings on RP pathology Systematic Review of Pretreatment Prostate-Specific Antigen Velocity and Doubling Time As Predictors for Prostate Cancer Vickers AJ at all, JCO, 2009 In summary, we have found little evidence that pretreatment PSA velocity or PSA doubling time are of value for early-stage prostate cancer. There is therefore no justification for the use of PSA dynamics in the clinical setting or as an inclusion criterion for clinical trials in this population.
Radical prostatectomy versus watchful waiting in early prostate cancer. Bill-Axelson A. at all: NEJM 2011 15 years follow up
Moratality in low risk disese Scandinavian trial vs Sunnybrook active surveillance. Klotz L, Thompson I; NEJM, 2011
Modified Gleason scoring 2005: Inflation of Grade Helpap B; Virchows Arch. 2006 Billis A.; J. Urol. 2008
Results of AS in screening detected PC
Long term quality-of-life outcomes after RP or WW: SPCG-4 randomised trial. Johanson E., Gunnar S; Laccet Oncol 2011 No difference in any measure of psychological functioning between RP and WW group at 12 years
AS what we can expect i future? Role of biomarkers: PCA3, HLK4, PHI, Aureon and other Multiparametric MRI (Biopsy?) MRI detected TRUS quided biopsy
Pathological findings correlation with PCA3
Why do we miss tumors on biopsy? Choi YJ et al.; radiographics 2007 Evidence: Radical Prostatectomy specimen MRI findings
Cognitive or software based guided biopsy? Artemis MedCom/Pi Medical BiopSee
Prostate cancer diagnosis : multiparametric MR-targeted biopsy Magnetic with cognitive resonance and transrectal imaging/ US-MR ultrasound-fusion guidance versus biopsy systematic significantly upgrades biopsy prospective prostate cancer multicenter versus systematic study. Puech 12-core P.. Radiology. transrectal 2013 ultrasound biopsy. Siddiqui MM, European Urology. 2013 10% increase in detection of prostate fusion-guided cancer in targets biopsy identified upgraded on MRI and and detected a 15% increase PCa of higher in high-grade Gleason disease, score in 32% compared of patients with systematic compared with biopsies traditional 12-core biopsy alone
What is the risk of significant cancer in a patient with negative MP MRI? Magnetic resonance imaging for prostate cancer comparative studies including radical prostatectomy specimens and template transperineal biopsy Toner L, Prostate International 2015 The sensitivity and specificity of mpmri reported in the literature is approximately 80-90% and 50-90% when compared to RP and TTPB specimens. This is less than what some expect, possibly reflecting a learning curve for the technique of mpmri.
MP MRI will it help? 64 AS pts. were prospectively followed with MP MRI at 3 and 12 months 9/64 (14%) were re-risk starified at 3 months 3/30 (10%) were re-risk stratified at 12 months A negative MP MRI (PiRAD 1 & 2) had NPV of 84% for all cancers and 100% for Gleason 4 or 5 patterns A PiRAD score of 4 or 5 had sensitivity of 92 % of detecting Gleason pattern 4 or 5 Hoeks et all. Value of 3-T multiparametric magnetic resonance imaging and magnetic resonanceguided biopsy for early risk restratification in active surveillance of low-risk prostate cancer: a prospective multicenter cohort study. Invest Radiol. 2014
Magnetic resonance-invisible versus magnetic resonance-visible prostate cancer in active surveillance: a preliminary report on disease outcomes. Dianat S et all, Urology 2015 The MR-invisibility of tumor on MP MRI could be of prognostic significance in monitoring men in AS with potential benefit of tailoring the frequency of surveillance biopsies and reducing the number of unnecessary biopsies. Urology 2015 85, 147-154DOI: (10.1016/j.urology.2014.06.085) Copyright 2015 Elsevier Inc. Terms and Conditions
Where are we? AS should be offered for Man with PSA <10 Gleason 6 (Low Risk) PSA kinetics only a guide for the decision Confirmatory biopsy (including anterior and anterolateral horn) within 1 year Repeat biopsy every 3-5 years depending on PSA, age, MRI risk tolerance MP-MRI for PSA DT <3 years or volume increase
Future of AS Screening image/risc factor based (fewer biopsies and less insignificant cancers) Avoidance of setting cancer diagnosis on low risk patients ( neoplasm of low malignant potential?) hence, less anxiety and depression Growing importance of better imaging and possibly new biomarkers to identify aggressive disease at the time of diagnosis