39 page PROSTATE DISEASE NEOPLASIA Presentation on CD

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TITLE:

 PROSTATE NEOPLASIA, 39 pages (slides)

SLIDE TOPICS, SUBTOPICS and CONTENTS:

 
PROSTATE NEOPLASIA
BENIGN PROSTATIC HYPERPLASIA
AND
PROSTATE CANCER
PROSTATE ANATOMY
fibromuscular tissue (30-50%)
glandular epithelial cells (50-70%)
peripheral zone (most cancers)
central zone
transition  zone (BPH,low grade cancers)

BENIGN PROSTATIC HYPERPLASIA
17% of men age 50-59 (require Rx)
27% of men age 60-69 (require Rx)
35% of men age 70-79  (require Rx)
Similar crosscultural prevalence
Some genetic and racial susceptibility to symptom severity (autosomal dominant)
Diet high in saturated fats, zinc and low in fruits and vegetables.
Sedentary life style.

BPH Proposed Etiologies
Reawakening of the urogenital sinus to proliferate
Change in hormonal milieu with alterations in the testosterone/estrogen balance
Induction of prostatic growth factors
Increased stem cells/decreased stromal cell death
BPH Pathophysiology
Slow and insidious changes over time
Complex interactions between prostatic urethral resistance, intravesical pressure, detrussor functionality, neurologic integrity, and general physical health.

BPH Pathophysiology
Initial hypertrophydetrussor decompensationpoor tonediverticula formationincreasing urine volumehydronephrosisupper tract dysfunction
BPH SYMPTOMS Obstructive and Irritative
Impairment of size/force of stream
Hesitancy
Intermittency
Terminal dribbling
Incomplete emptying
Nocturia
Frequency
Urgency
Dysuria

Other  late presenting signs/symptoms
Abdominal/flank pain with voiding
Uremiafatigue,anorexia,somnolence
Hernias, hemorroids, bowel habit change
UTI’s
Bladder calculi
Hematuria
Other Relevant History
GU History (STD, trauma, surgery)
Other disorders (eg. neurologic, diabetes)
Medications (anti-cholinergics)
Functional Status
BPH Clinical Findings
Late signs of renal failure ( eg. anemia, HTN)
Abdominal examhydronephrosis/pyelonephritis
GU exam hernia, stricture, phimosis, cancer
DRE a smooth enlargement, “non-palpable” nodularity with a loss of distinction between the lobes. A soft/firm consistency,underestimates enlargement, can’t feel seminal vesicles

BPH Danger Signs on DRE
Firm to hard nodules
Irregularities, unequal lobes
Induration
Stony hard prostate
Any palpable nodular abnormality suggests cancer and warrants investigation
BPH Clinical Evaluation
AUA Score to assess sx severity but NOT for DDX
DRE for prostate size, consistency,nodules, asymmetry, rectal tone and focused neuro exam
Abdominal/GU exam

UA, lytes (BUN,Creat.) PSA(interpret carefully)
Uroflowmetry/residual urine measure
Upper tract evaluation if hematuria, increased creatinine
Ultrasound
Cystoscopy
Urine cytology


BPH SYMPTOMS Differential Diagnosis
Urethral stricture
Bladder neck contracture
Carcinoma of the prostate
Carcinoma of the bladder
Bladder calculi
Urinary tract infection and prostatitis
Neurogenic bladder
BPH Natural History
A progressive condition (usually) with histological onset in the 30’s and worse with age
A 50 yo has a 20-25% lifetime chance of needing a prostatectomy
A 40 yo who lives to 80 has a 30-40% chance of prostatectomy
But these numbers will change with new medical Rx and one third of patients improve on their own
Higher initial PSA’s predict faster growth and higher risk of acute urinary retention
BPH TREATMENT INDICATIONS Absolute vs Relative

Severe obstruction
Urinary retention
Signs of upper tract dilatation and renal insufficiency

Moderate symptoms of prostatism
Recurrent UTI’s
Hematuria
Quality of life issues
ONE POSSIBLE APPROACH (use cautiously)
BPH TREATMENT NON-SURGICAL
Watchful waiting, AUA score < 7, 1/3 improve on own.
Herbal Phytotherapy (eg. Saw Palmetto)
Alpha-1-adrenergic antagonists (terazosin,doxazosin,tamsulosin,alfuzosin)
5-Alpha-reductase inhibitors (finasteride,dutasteride)
Combination Rx most effective for most severe.
Medical Rx has likely reduced Medicare claims for BPH surgery by 50%.
BPH TREATMENT Surgical
Indicated for AUA score >16
Transurethral Prostatectomy(TURP): 18% morbidity with .2% mortality. 80-90% improvement at 1 year but 60-75% at 5 years and 5% require repeat TURP.
Transurethral Incision of Prostate (TUIP): less morbidity with similar efficacy indicated for smaller prostates.
Open Prostatectomy: indicated for glands > 60 grams or when additional procedure needed for suprapubic/retropubic approaches
BPH TREATMENT New Modalities
Minimally invasive: (Prostatic Stents,TUNA,TUMT, HIFU,Water-induced Thermotherapy)
Laser prostatectomy (VLAP,ILC,CLAP,TULIP,HoLRP)
Electrovaporization (TUVP,TVRP)

PROSTATE CANCER Incidence/Prevalence
Most common cancer in men. In the year 2000, 200K men were diagnosed and 30K died from the disease.
21% of all cancers.
Increased risk with age with 30% presenting between age 70-79 and 67% between age 80-89.
Slowly progressive (as a rule): low gradegood prognosis, high gradepoor prognosis, and moderate gradevariable prognosis.
PROSTATE CANCER Possible etiologies/risk factors
Age is the most important risk factor.
Genetic predisposition/ racial and family history.
Diet risk: high animal fat, high zinc, low vegetable and low fish(omega-3 fatty acids) intake, low selenium intake, low fruit, low vegetable intake.
Hormonal risk: high testosterone, high insulin, and high insulin-like growth factor.
Low UV light exposure, high pesticide exposure.
No increase in risk with BPH or vasectomy.
? Protection from ASA, statins.

PROSTATE CANCER Screening
DRE: can detect tumors in the posterior and lateral aspects of the gland. Can detect extension. Accuracy depends on experience of examiner.
PSA: must be interpreted in clinical context, higher sensitivity and lower specificity than DRE.
 Referral for TRUS and/or sextant biopsy if DRE or PSA abnormal.
PPV for PSA >4 or DRE is ~30%.
Screening is controversial. No consensus. Morbidity and mortality data inconclusive. Informed discussion with patient is essential.


Prostate Cancer Screening ACP Discussion Points
Prostate cancer is an important health problem.
The benefits of one-time or repeated screening and aggressive treatment of prostate cancer have not yet been proven.
DRE and PSA measurements can have both false-positive and false-negative results.
The probability that further invasive evaluation will be required as a result of testing is relatively high.
Aggressive therapy is necessary to realize any benefit from the discovery of a tumor.



Prostate Cancer Screening ACP Additional Discussion Points
A small but finite risk for early death and a significant risk for chronic illness, particularly with regard to sexual and urinary function, are associated with these treatments.
Early detection may save lives.
Early detection and treatment may avert future cancer-related illness.



Prostate Cancer Screening and Treatment (the key question)
“is cure possible in those for whom it is necessary, and is cure necessary in those for whom it is possible?”

Dr. Willet Whitmore, 1990
AUA 2007 Annual Meeting
“Men are presenting at a younger age and lower stage. We are seeing fewer and fewer biochemical recurrences, and when they do occur, they are less lethal. Thousands of papers support this.”

Dr..  Anthony D’Amico,
Dana Farber Cancer Center
“Reasonable” Recommendations in 2007 for Prostate Screening
Yearly risk/benefit discussions for all men starting at age 50 who are expected to live 10 years. For blacks and those with + family hx start at 40-45.
If decision to screen: yearly DRE/PSA until co-morbidities/age (75) limit life expectancy to 10 yrs
Immediately refer if  abnormal DRE or PSA>7.
Repeat PSA between 4 -7 several weeks later and refer if still >4.
If PSA <4, refer men who experience a PSA rise of more than .75 ng/mL/year (based on last three measurements obtained over 12 to 24 months).


THE ROLE OF PSA Possible Refinements
Consider age and race adjustments.
PSA density(TRUS adjusted PSA).
PSA velocity (rate of change of  PSA)(>.75 ng/mL/yr).
Free/Bound PSA values may be useful in separating elevations in PSA from BPH vs cancer.
Interval recommendations may change, depending on age and PSA level.

More PSA Refinements
Delay performing test 48 hours after recent ejaculation or local trauma and wait at least 6 weeks after biopsy or TURP.
If PSA elevated wait 2-4 weeks and repeat to confirm. Some experts recommend antibiotics before repeat.
PROSTATE CANCER Signs
Stony hard prostate.
Hematuria, hematospermia.
Irregular, firm, hard nodule on DRE.
Signs of obstructive uropathy/Rising AUA Score.
Neurologic cord compression signs.
Pathologic fractures/Bone pain.
Sudden onset of erectile dysfunction, painful ejaculation.
PROSTATE CANCER Diagnosis
Prostate biopsy by FNA or Biopty.
33-50% chance of biopsy being malignant.
Differential Diagnosis: BPH, chronic prostatitis, prostatic TB, old biopsy fibrosis, prostatic cysts, prostatic calculi.
PROSTATE CANCER Clinical Staging
DREsize, location, volume, local extension
TRUS/Endorectal coil MRIlocal extension
CT/ProstaScint Scanpre-op pelvic node assessment
Pelvic Lymphadenectomypelvic nodes
Other Tumor Markers
PSAhighest in transition zone tumors and well differentiated tumors. Its greatest value is in detecting recurrence
Bone Scanmets
PROSTATE CANCER STAGING TMN Staging & Gleason Scale

T1 are microscopic and non-palpable
T2 are palpable but confined to gland
T3 protrude beyond the gland capsule
T4 are fixed and extend well beyond the gland

Based on tumor histology
Grade 1 Gleason is the most well-differentiated
Grade 5 is the most poorly differentiated
Combined scores are reported (primary +secondary)(2-10)
PROSTATE CANCER Treatment Options for Clinically Localized Disease

Radical prostatectomy
Radiation therapy (external beam or interstitial implantation)
Watchful Waiting
Possible hormonal therapy (ADT) is mostly used for locally advanced or metastatic disease. (Neoadjuvant ADT with Radiation may improve outcomes for men with intermediate/high pathological risk localized cancer.)

MOST IMPORTANT TREATMENT ISSUES
Patient’s medical condition/age.
Gleason Grade and PSA.
Is it Organ Confined?/Stage.
Estimation of outcome for individual patient.
Potential side effects of treatments.
Greatest treatment benefit-> “moderate to poor grade cancers in younger, healthier age group.”
Least treatment benefit-> “lower grade cancers in older, sicker age group.”
MOST IMPORTANT POINTS FOR THE FAMILY PRACTITIONER

For BPH: It is mostly a primary care disease for both diagnosis and treatment. Know the danger signs and when to refer.
For Prostate Cancer: Screening and Rx may be controversial, but something is making a difference. All patients deserve an informed discussion about options.