Prostate Cancer Screening PSA and Beyond The Skinny PSA types PSA facts New tests Guidelines 1
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 2
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 3
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 4
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. 5
Staging/Surveillance Before radical prostatectomy Predict outcomes tumor volume grade of disease biochemical progression Surveillance marker for recurrent disease PSA doubling time post prostatectomy Hormone therapy CRPCa Monitoring 6
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 7
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. 8
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 mrna protein PCA3 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 9
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 10
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% 11
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 12