Mr Jeremy Grummet, Urological Surgeon MBBS, MS, FRACS Foundation 49 Men s Health Symposium August 2015

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1 Mr Jeremy Grummet, Urological Surgeon MBBS, MS, FRACS Foundation 49 Men s Health Symposium August 2015

2 The dilemma Most men die with prostate cancer rather than of prostate cancer BUT Some prostate cancer is lethal 2nd highest cause of cancer death in Australian men AIHW 2013

3 The aim Find the prostate cancers with lethal potential when still curable Avoid treatment (and diagnosis) of the prostate cancers that are harmless

4 Diagnosis Pre-PSA era Advanced disease common year survival was 59% PSA introduced in 1990s Low risk disease now more common year survival 90% Mortality rate declining AIHW 2013

5 PSA screening Large RCTs gave conflicting results Best evidence suggests population screening reduces mortality slightly and morbidity modestly But, due to risks outweighing benefits, population screening program not currently recommended Instead, many guidelines advocate a discussion between individual men in 50s and 60s and their GP re pro s and con s of PSA testing NEJM 2009 AUA, ACS, EAU, USANZ

6 Risks of PSA screening Elevated PSA Well man TRUS biopsy Invasive procedure Low risk prostate cancer Major surgery Radical prostatectomy Reduced QoL Erectile dysfunction

7 Risks of PSA screening PSA is not specific for prostate cancer Elevated PSA leads to prostate biopsy, which is required to diagnose prostate cancer Most commonly performed technique is TRUS biopsy

8 Risks of TRUS biopsy Nearly 1/2 of TRUS biopsies are negative for cancer No cancer Cancer missed Pain OR Often leads to multiple repeat TRUS biopsies Anxiety re result Sepsis 2% in Victoria in 2012 VAED

9 Risks of TRUS biopsy Of TRUS biopsies positive for cancer, 1/4 are low risk disease Previously all underwent treatment Most of these are harmless tumours Despite this, 60% of low risk cancer patients undergo curative treatment in Victoria 90% in USA PCR, MJA 2013

10 Risks of curative treatment Surgery or radiotherapy QoL side effects Erectile dysfunction Urinary incontinence and other LUTS Rectal symptoms

11 Addressing the risks Smarter use of PSA Multiparametric MRI Transperineal biopsy Active surveillance

12 Smarter use of PSA Target men in 50s and 60s Life expectancy > 15 years Single elevated PSA should not lead to immediate biopsy Repeat if elevated Aberrant readings common Add free-to-total ratio, PHI Use PSA velocity and PSA density

13 Addressing the risks Smarter use of PSA Multiparametric MRI Transperineal biopsy Active surveillance

14 Multiparametric MRI Until now, no imaging to reliably detect prostate cancer We still perform blind random biopsies of a whole organ Kidney cancer analogy Recent profusion of evidence of diagnostic accuracy of mpmri Combination of multiple parameters T2, DWI, DCE Standardised reporting - PIRADS

15 Multiparametric MRI

16 Multiparametric MRI

17 Multiparametric MRI Not only increases detection of significant cancer Also has potential to reduce detection of low risk cancer This is exactly what we have been searching for in prostate cancer diagnosis the holy grail Australia leading the way

18 Multiparametric MRI Wesley Hospital Brisbane Compared mpmri targeted biopsy to 12 core TRUS biopsy MpMRI far outperformed TRUS biopsy NPV for significant prostate cancer mpmri 97% (only missed 3%) TRUS biopsy 72% (missed 28%) If only mpmri pathway was used Reduce need for biopsy by 51% Reduce diagnosis of low risk cancer by 89% Increase detection of significant cancer by 18% Limitation of study is comparison against 12 core TRUS biopsy NPV of 97% probably an overestimate Pokorny et al, European Urology 2014

19 Multiparametric MRI St Vincent s Hospital Sydney Compared mpmri targeted biopsy to 30 core transperineal biopsy NPV for significant prostate cancer mpmri 92% (only missed 8%) If only mpmri pathway was used Reduce need for biopsy by 50% (same as Brisbane) Reduce diagnosis of low risk cancer by 34% - Compared to 89% in Brisbane study - But still substantial reduction Thompson et al, J Urology 2014

20 Multiparametric MRI A genuine breakthrough in prostate cancer Already incorporated into 2014 UK NICE guidelines Challenges How to ensure quality reporting How to be cost effective Where to insert into diagnosis and surveillance algorithms Whether biopsy can safely be prevented if mpmri negative

21 Addressing the risks Smarter use of PSA Multiparametric MRI Transperineal biopsy Active surveillance

22 Transperineal biopsy No breach of rectal wall Sepsis risk exceedingly small 0.076% in literature (1.7% - 5% for TRUS) Zero in our own series of >450 patients Avoid use of prophylactic broad spectrum antibiotics Help reduce development of superbugs Fixed grid enables stability to perform targeted biopsies Grummet et al, BJUI 2014

23 Addressing the risks Smarter use of PSA Multiparametric MRI Transperineal biopsy Active surveillance

24 Active surveillance Avoids unnecessary treatment of low risk cancer PSA <10, not palpable on DRE, low volume Gleason 6 Currently requires repeat confirmatory biopsy within 12 months of diagnosis Based on a blind 12 core TRUS biopsy (not 24+ core transperineal) Pre advent of mpmri

25 Active surveillance If no sign of disease progression, continue to monitor with PSA, DRE Cancer upgraded in 28% at repeat biopsy These patients switched to curative treatment (but majority continue on AS) Critics cite upgrading as evidence of concern for AS AS can be improved by more accurate initial diagnosis with mpmri Less diagnosis of low risk cancer Less overall need for AS Expect less upgrading of disease during AS Higher proportion remain on AS PRIAS study 2013

26 Addressing the risks Smarter use of PSA Multiparametric MRI Transperineal biopsy Active surveillance

27 Take home message - 1 Diagnosis of prostate cancer has been terribly inaccurate Diagnosis is now finally becoming accurate Smarter use of PSA Multiparameteric MRI Transperineal biopsy

28 Take home message - 2 Morbidity of diagnosis itself has been significant Morbidity of diagnosis is being reduced Smarter use of PSA Transperineal biopsy

29 Take home message - 3 Low risk prostate cancer has been grossly overtreated Overtreatment of low risk disease is being reduced Multiparametric MRI Transperineal biopsy Active surveillance

30 Exciting times! Thank you

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