Prostate Cancer detecting prostate cancer PSA, Free PSA, proPSA (or PSA2) Differentiate prostate cancer

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  • Prostate Cancer

    David Wilkinson MD

    Gulfshore Urology

  •  Male Sexual Gland

     Adds nutrients and fluids for sperm

     This fluid is added to sperm during ejaculation

     Urethra (urine channel) runs through the middle of the prostate

    What is the Prostate?

  •  Abnormal cells growing out of control

     Spreads and invades local tissues

     Prostate Cancer ◦ Begins with a small tumor in the gland

    ◦ First spreads to the local lymph nodes

    ◦ Then spreads to the bony skeleton and other areas of the body

    What is Prostate Cancer?

  •  Prostate Cancer ◦ Leading type of cancer in men (1 in 6) ◦ Second leading cause of death in American males ◦ Over 40,000 deaths each year in the United States

     Recent alarming increase in diagnosis of advanced cancer secondary to less screening in men over 70.

     Early Detection ◦ Best prognosis is early detection ◦ lower mortality rates of prostate cancer with early

    detection ◦ Affords patients with many options for treatment

    Prostate Cancer Facts

  •  Birth to 39 0.01% (1 in 12,833)

     40 to 59 2.28% (1 in 44)

     60 to 79 14.20% (1 in 7)

     Birth to Death 17.15% (1 in 6)

    Probability of Developing Invasive Prostate Cancer at Various Ages

  •  Two tests used in combination for early detection previously ◦ Prostate Specific Antigen (PSA) test ◦ Digital Rectal Exam (DRE) Combined with PSA because it is generally less effective Now DRE, Prostate Health index , 4K scoreand

    multiparametric MRI of prostate, PCA 3, Select MDX, Iso

     Only tissue biopsy confirms a diagnosis of cancer ◦ Tissue sample is obtained by needle, guided by

    transrectal ultrasound

    Prostate Cancer Detection

  • PSA (Prostate specific antigen)

     Gamma seminoprotein or Kallikrein KLK3

     Secreted by normal epithelial cells in prostate and also by prostate cancer cells

     In healthy prostate tissue, liquefies ejaculate to allow sperm motility and thins cervical mucous

     Originally approved by FDA in 1986 to monitor PROGRESSION of known prostate cancer

  •  FDA approved in 1994 to screen asymptomatic men IN COMBINATION WITH DRE

  • THE PROBLEMS WITH PSA

     Can be elevated for MANY reasons that are NOT prostate cancer

     Benign prostatic hyperplasia, urinary tract infection, prostatitis, urinary retention, recent catheterization of the bladder, recent prostate surgery, mechanical agitation of the prostate (ejaculation, long distance cycling)

     Can lead to false positives (elevated PSA and NO cancer) causing anxiety and unecessary biopsies

  •  Can lead to false negatives (PSA level normal with cancer present) causing delayed diagnosis and possible morbidity/mortality from prostate cancer

  •  3x more specific than total or free PSA in detecting prostate cancer

     PSA, Free PSA, proPSA (or PSA2)

     Differentiate prostate cancer from benign prostate conditions that elevate PSA

     decrease unecessary prostate biopies by 26%

     Increase probability of finding prostate cancer and identifying aggressive cancers (Gleason 7 or greater)

    Prostate Health Index (PHI)

  • 4 K score

     Blood test  Research on > 10,000 patients at Memorial Sloan Kettering  4 kallikreins : Total PSA, Free PSA, Intact PSA and

    kalliekrein hk2  The 4 kallikreins combined in algorithm with age, DRE

    findings, Family Hx, prior biopsy results (if available)  Reported as percentage risk of aggressive prostate cancer

    (Gleason 7 or greater)

  •  Created for men with elevated PSA, abnormal DRE or continued PSA elevation after prior negative prostate biopsy

  • PCA 3 (prostate cancer antigen 3)

     Urine test

     First urine specimen after DRE

     mRNA only expressed in human prostate tissue

     Highly overexpressed in prostate cancer

     Most useful when evaluating continued elevated PSA after negative prostate biopsy

  • Select MDx

     Urine test

     First urine after DRE

     mRNA of DLX1 and HOXC6 combined with algorithm including PSA , age, family history or prostate cancer

     Elevation of DXL1 and HOXC6 are associated with increasing probability or Gleason grade 7 or greater prostate cancer

     Combined with PSA (KLK3) to determine need for initial biopsy or repeat biopsy

  • ExoDx (Prostate (intelliscore)

     Urine test

     NO DRE required

     PCA3, ERG, SPDEF all increased in expression with prostate cancer

     In men > 50 with PSA between 2 to 10, 94% negative predictive value for Gleason grade 7 or greater prior to first biopsy

     Accurately predicted stage and aggressive Gleason score prostate cancers prior to prostatectomy (pathology correlated)

  •  Has a score reported 0 to 100

     Score of greater than 15.6 (binary cut point) at increased risk of Gleason grade 7 prostate cancer or greater

  • Conclusion

     Currently no test REPLACES PSA

     Many new minimally invasive tests can be used to AUGMENT PSA

     PSA combined with testing discussed allows best determination of who is at risk for high grade prostate cancer and who truly needs prostate biopsy or to progress to treatment from active surveillance

  • Diagnosis of Prostate Cancer Staging

  •  Most often used for prostate biopsy

     Not recommended as a routine test for the early detection of prostate cancer

    Transrectal Ultrasound

  •  Done with endorectal coil

     Multi phase study which identifies areas within prostate that are concerning for prostate cancer

     Can differentiate between benign growth, infection/inflammation and cancer

     Allows for targeted biopsy of prostate

     Potential for focal treatment in the future

    MRI of prostate

  •  Uses images obtained from prostate MRI with endorectal coil

     MRI images fused to ultrasound used during biopsy

     3 dimensional real time graphic imaging of biopsy and mapping of biopsies

     Increases sensitivity of cancer detection

     Allows for focal biopsy of only abnormal areas

    UroNav Prostate biopsy

  •  The pathologist assigns the Gleason score to grade the cancer

    ◦ Low grade (6 points): slow growth

    ◦ Middle grade (7 points): intermediate growth

    ◦ High grade (8-10 points): most aggressive form of cancer

    Biopsy and Gleason Score: Good and Bad Grades

  •  Cannot be felt

     T1a – cancer found in < 5% TURP specimen

     T1b – cancer found in > 5% TURP specimen

     T1c – cancer found as a result of PSA elevation only

    Prostate Cancer T1 disease

  •  Can be felt during DRE (digital rectal exam)

     T2a – felt on less than ½ of one side of the prostate

     T2b – felt on over half of one side of the prostate

     T2c – felt on both sides of the prostate

    Prostate Cancer T2

  •  Has spread beyond the prostate

     T3a – extra capsular extension

     T3b – tumor invades seminal vesicle(s)

    Prostate Cancer T3

  •  Cancer has invaded local organs

     Bladder invasion

     Invasion into surrounding pelvic side wall

     May cause pain in joints and back

    Prostate Cancer T4

  •  Dependent upon…

    ◦ Stage of the disease

    ◦ Patient’s age and health

    ◦ Patient’s personal preference

    Treatment Options

  •  No treatment given initially

     Reserved for people with

    ◦ Non-aggressive cancer

    ◦ Overall poor health

     Close follow-up, included repeat biopsies, PHI,

    and genetic testing of initial prostate biopsies

     Delayed hormone therapy

    Watchful Waiting/Active Surveilence

  •  Without testosterone production at puberty, the prostate gland would not develop

     In adults, prostate growth stops in the absence of the male hormone, testosterone

     Prostate cancer usually stops when the testes are removed because prostate tissue and prostate cancer are uniquely sensitive to testosterone

    Hormone Therapy: Background

  •  Treatment for localized prostate cancer

     Recurrent prostate cancer

     Cancer cells are destroyed by freezing

     A heated catheter minimizes damage to surrounding tissue

     Outpatient procedure

     Risk of ED and incontinence

    Cryosurgery

  •  Uses radiation to kill cancer cells

     Various types

    ◦ External beam radiation therapy  Intensity-modulated radiation therapy (IMRT)  Image guided radiation therapy (IGRT) Rapid arc, radiation delivered in 360 degree fashion

    ◦ Brachytherapy Seed implantation High dose rate (HDR)

    Cyberknife Gamma Radiation Created by neurosurgeon for inoperable brain tumors Used