Prostate Cancer Screening Dr. J. McCracken, Urologist
USPSTF Lifetime risk for diagnosis currently estimated at 15.9% Llifetime risk of dying of prostate cancer is 2.8% Seventy percent of deaths due to prostate cancer occur after age 75 years
PSA problems (USPSTF) 80% of positive PSA test results are falsepositive (2.5 4.0) Triggered biopsys have 1/3 complication rate 1% serious
USPSTC Summary Although the precise, long term effect of PSA screening on prostate cancer specific mortality remains uncertain, existing studies adequately demonstrate that the reduction in prostate cancer mortality after 10 to 14 years is, at most, very small, even for men in what seems to be the optimal age range of 55 to 69 years
Surveys on USPSTF 20% of men aware 75% of men disagree After reading the study 73% disagree still 47% believe GP recommended it 51% had a pro/con discussion 97% of people said the did not receive enough information
Recent Arguments European Randomised Study of Screening for Prostate Cancer 50 and 74 years from eight countries PSA screening every 4 years vs none Biopsy for PSA > 3.0
Results At 9 years 15% reduction in PCa deaths At 11 years 22% reduction in PCa deaths Overall at 13 years screened men 27% less likely to die of prostate Ca
Number needed to save 1 life At 9 years 1,410 NNS Treated = 48 for 1 life saved At 13 years 781 Treated = 27 for 1 life saved Number presenting advance stage lower in screened group Overtreatment in 40% of cases
To PSA or not to PSA
The Skinny PSA types PSA facts New tests Guidelines
Total PSA Produced primarily by the human prostatic epithelium PSA is normally secreted in high concentrations into seminal fluid Functions in the liquefaction of the seminal coagulum It is organ specific but not disease specific Can be detected in patients with normal prostate and benign prostatic hyperplasia (BPH)
Disruption of basement membrane integrity prostatic infarction prostatitis ejaculation 15% 48hrs digital rectal manipulation (DRE) 0.26 to 0.4 ng/ml 24 hours prostatic instrumentation Up to 50x, may take months
Proof of effect in 1991 PSA + DRE vs PSA = +27% PSA + DRE vs DRE = +34% Catalona et al
Role in Screening Major cancer organizations = no universal agreement on the relationship between early detection and survival Most urologist believe the problem is not overdetection but overtreatment Shared decision Individualized screening prostaterisk.ca No screening = aggressive tumors present advanced
PROSTATE RISK CALCULATOR Age: range (30 90) IPSS(Urinary voiding Symptom score): range (0 35) PSA: range (0.1 50) FTPSA (Free:total PSA ratio): range(0.01.99) Ethnic Background: Asian Caucasian African Desent Other Family history of prostate cancer: Abnormal DRE(by Doctor): Yes No
Age:39 IPSS:13 PSA:2.6 FTPSA (Free:total PSA ratio):0.14 Ethnic Background:Caucasian Family history of prostate cancer:yes Abnormal DRE(by Doctor):No
Predicting Outcomes If younger than 60 0.7 0.9 ng/ml > age corrected N Lifetime increased risk of prostate cancer < 1.0 ng/ml low lifetime risk of metastasis and death from prostate cancer may harbor prostate cancer disease is unlikely to become life threatening?screened on a biennial or triennial basis.
Staging/Surveillance Before radical prostatectomy Predict outcomes tumor volume grade of disease biochemical progression Surveillance marker for recurrent disease PSA doubling time post prostatectomy
Monitoring Hormone therapy CRPCa
PSA density PSA / volume Larger prostates = higher PSA Most helpful 4.0 10 range Subsequent data shows flaws Volume measurements Stromal composition Biopsy sensitivity in large prostates Active surveillance role
PSA Velocity Serial PSA measurements greater than 0.75 ng/ml/year increase both the positive predictive value of PSA testing and the likelihood of diagnosing cancers while they are organ confined Not totally reliable when differentiating between benign and malignant disease
Free/Total 25% of biopsies are positive with PSA 2 10 F/T ratio 0 10% 55% to 56% bx + F/T > 25% 8% bx + Larger prostate less likely helpful Can be helpful very high or very low in men smaller glands negative biopsies high total PSA levels.
NEW MARKERS! PRO PSA Assd with higher Gleason score Active surveillance role Mens Health Index F/T PSA, propsa Sensitivity 90% Specificity 31.6% Human kallikrein related peptidase 2 PSA family 4Kscore 80% sensitive, specificity unclear
PCA3 mrna protein 95% of prostate cancer tissues 6x increase First void urine (20 to 30 ml) is collected immediately after a digital rectal exam RT PCR Not influenced by prostate volume Negative <35 = Low risk
PCA3 Sensitivity 77% Specificity 57% If previously biopsied and negative PCA3 ~4.5x less likely to have a positive rebiopsy Outperforms PSA on predicting prostate cancer prior to first biopsy
MRI New technology in Victoria Used if suspicion of PCa and previous negative biopsy Improves biopsy sensitivity Future unknown
Gene Fusion TMPRSS2 ERG gene fusion (T2E) 50% of all cases Urine test possible Sensitivity 45% Specificity 86% Suspect has prognositic value
The whole enchilada!!! T2E + PCA3 PSA + PCA3 = Mi Prostate (MiPS) score 10% = risk of positive biopsy Sens = 80%, Specificity = 90%
Summary PSA screening still of value New tests coming, some here Unification of strategies needed PSA values need to be interpreted Overdiagnosis vs overtreatment
Canadian Guidelines Offered to all men over 50, annually Over 40 if risk factors (African descent, family history) Baseline in 40 s may be of benefit Must have 10 year life expectancy AUA guidelines suggest that q2y likely OK if previously screen, some studies say q4y Cutoff at age 70 unless very healthy
What s the discussion? http://www.cancer.gov/cancertopics/pdq/scre ening/prostate/patient/page4
Finding prostate cancer may not improve health or help a man live Mets longer Overdiagnosis (non life threatening ca) Stress related death (CVD, suicide) Greatest in first year after Dx
Follow up tests, such as a biopsy, may be necessary Complications Fever, hematuria, hematospermia, UTI False negative PSAs False positive PSAs