1. BENIGN PROSTATIC HYPERPLASIA

2. Zonal Anatomy of the Prostate
Peripheral zone
70% of volume of young adult prostate
60-70% of CaP
Central zone
25%: young adult prostate
5-10% of CaP
Transition zone
5%: young adult prostate
10-20% of CaP
Benign Prostatic Hyperplasia

3. Incidence & Epidemiology
most common benign tumor in men
age related incidence
prevalence
20% (41–50 y/o)
50% (51–60y/o)
>90% (>80y/o).
age related symptoms (prostatic obstruction)
age 55 = 25% obstructive voiding symptoms
age 75 = 50% ↓ force & caliber of urinary stream.

4. Risk factors: Etiology Genetics Race
~50% of men < 60 y/o (autosomal dominant)
↑ relative risk 4x in 1° ♂ relatives
Race
Etiology
multifactorial and endocrine controlled
stromal and epithelial elements  hyperplastic nodules
positive correlation between levels of free testosterone and estrogen and the volume of BPH

5. Pathology hyperplastic process  ↑ in cell number  (cont.)
Microscopic evaluation: nodular growth pattern that is composed of varying amounts of:
Stroma
Collagen (non-responsive to either form of medical therapy)
smooth muscle (alpha-blocker therapy)
epithelium (5-alpha-reductase inhibitors)
 enlarged BPH nodules  compress outer prostate zones = surgical capsule
separates TZ from PZ
cleavage plane for open enucleation of the prostate during open simple prostatectomies performed for BPH.

6. Pathophysiology obstructive component of the prostate
mechanical
prostatic enlargement  intrusion into the urethral lumen or bladder neck  obstruction  high bladder outlet resistance
dynamic obstruction
variable symptomatology
prostatic stroma is rich in adrenergic nerve supply
level of autonomic stimulation thus sets a tone to the prostatic urethra
alpha-blocker therapy  ↓ tone  ↓ outlet resistance.
secondary response of the bladder to the outlet resistance
irritative voiding complaints
Bladder outlet obstruction  detrusor muscle hypertrophy and hyperplasia; collagen deposition  mucosal herniation bet. Detrusor muscle bundles  FALSE DIVERTICULA (mucosa and serosa only)
Cystoscopic examination: trabeculation (thickened detrusor muscle bundles)

7. Clinical Findings Symptoms: Obstructive Irritative
Hesistancy
↓ force and caliber of stream
Sensation of incomplete bladder emptying
Double voiding
Straining to urinate
Post-void dribbling
Irritative
Frequency
Urgency
Nocturia
AUA Symptom Score questionnaire
Single most important tool used in the evaluation of patients with BPH
recommended for all patients before the initiation of therapy

8. 0-7: mild 8-19: moderate 20-35: severe
7 items that ask patients to quantify the severity of their obstructive or irritative complaints on a scale of 0–5
0-7: mild
8-19: moderate
20-35: severe

9. Signs: Lab Findings: PE, DRE and neurologic exam
Smooth, firm, elastic enlargement of the prostate
Induration: possibility of cancer
Lab Findings:
Urinalysis
Exclude infection/hematuria
Serum creatinine
Assess renal function
Serum PSA (optional)

10. Imaging: Intravenous pyelogram or renal US
only in the presence of concomitant urinary tract disease or complications from BPH(hematuria,UTI)
Cystoscopy (not recommended)
may assist in choosing the surgical approach in patients opting for invasive therapy
Cystometrograms and urodynamic profiles
patients with suspected neurologic disease or those who have failed prostate suregery

11. Differential Diagnosis
urethral stricture, bladder neck contracture
Hx of previous urethral instrumentation, urethritis, or trauma
bladder stone
Hematuria and pain
CaP
DRE abnormalities or an elevated PSA
UTI
Mimic irritative sx of BPH
Urinalysis
Can be a complication of BPH
bladder carcinoma
irritative voiding complaints
urinalysis: hematuria
Neurogenic bladder d/o
hx of neurologic disease, stroke, DM, or back injury
↓ perineal or LE sensation or alterations in rectal sphincter tone or the bulbocavernosus reflex.

12. Treatment A. Watchful Waiting B. Medical Therapy
With mild symptoms (0-7)
Optional: moderate/severe symptoms
B. Medical Therapy
C. Conventional Surgical Therapy
D. Minimally Invasive Therapy

13. Absolute surgical indications
refractory urinary retention (failing at least one attempt at catheter removal)
recurrent UTI from BPH
recurrent gross hematuria from BPH
bladder stones from BPH
renal insufficiency from BPH
large bladder diverticula

14. Medical Therapy Alpha-blockers 5-Alpha-reductase inhibitors
contractile properties of the prostate and bladder neck mediated primarily by the subtype alpha-1areceptors
5-Alpha-reductase inhibitors
Blocks testosterone dihydrotestosterone
Epithelial component; ↓ size of gland and improvement of sx
6 months of tx

15. Medical Therapy Combination Therapy Phytotherapy
Doxasozin + Finasteride
Patients most likely to benefit : those with larger glands and higher PSA values
Phytotherapy
Use of plants or plant extracts for medicinal purposes
saw palmetto berry, (Serenoa repens) , the bark of Pygeum africanum, the roots of Echinacea purpurea and Hypoxis rooperi, pollen extract, leaves of the trembling poplar.
S. repens: most well-studied agent usually at 320 mg/day.

16. Conventional Surgical Therapy
Transurethral resection of prostate (TURP)
Risks : retrograde ejaculation (75%), impotence (5–10%), and incontinence (<1%)
Complications: bleeding, urethral stricture or bladder neck contracture, perforation of the prostate capsule with extravasation
TUR syndrome: hypervolemic, hyponatremic state due to absorption of the hypotonic irrigating solution
Transurethral incision of the prostate
moderate to severe symptoms and a small prostate often have posterior commissure hyperplasia (elevated bladder neck)
More rapid and less morbid than TURP
two incisions using the Collins knife at the 5- and 7-o’clock positions. The incisions are started just distal to the ureteral orifices and are extended outward to the verumontanum
TUR syndrome nausea, vomiting, confusion, hypertension, bradycardia, and visual disturbances.
risk of the TUR syndrome increases with resection times >90 minutes. Treatment includes diuresis and, in severe cases, hypertonic saline administration.

17. Conventional Surgical Therapy
Open Simple Prostatectomy
When prostate is too large to be removed endoscopically: open enucleation (glands >100 g)
Open prostatectomy: concomitant bladder diverticulum or a bladder stone is present or if dorsal lithotomy positioning is notpossible
Simple suprapubic prostatectomy
Transvesically
Operation of choice in dealing with concomitant bladder pathology
Simple retropubic prostatectomy
the bladder is not entered
A transverse incision is made in the surgical capsule of the prostate, and the adenoma is enucleated

18. Minimally Invasive Therapy
Laser Therapy
Two main energy sources of lasers have been utilized—Nd:YAG and holmium:YAG.
coagulation necrosis techniques: Transurethral laser-induced prostatectomy (TULIP) with TRUS guidance.
Visual contact ablative techniques: more time-consuming procedures because the fiber is placed in direct contact with the prostate tissue, which is vaporized

19. Minimally Invasive Therapy
Interstitial laser therapy places fibers directly into the prostate, usually under cystoscopic control;
may result in fewer irritative voidingsymptoms, because the urethral mucosa is spared and prostate tissue is resorbed by the body rather than sloughed
Advantages of laser surgery :
minimal blood loss
rare instances of TUR syndrome
ability to treat patients receiving anticoagulation therapy
ability to be done as an outpatient procedure.
Disadvantages
lack of availability of tissue for pathologic examination
longer postoperative catheterization time
more irritative voiding complaints
High cost of laser fibers and generators.

20. Minimally Invasive Therapy
Transurethral electrovaporization of the prostate
uses the standard resectoscope but replaces a conventional loop with a variation of a grooved rollerball.
High current densities cause heat vaporization of tissue, resulting in a cavity in the prostatic urethra.
Hyperthermia
Microwave hyperthermia is most commonly delivered with a transurethral catheter.
Transurethral needle ablation of the prostate
uses a specially designed urethral catheter that is passed into the urethra.
Interstitial radio frequency needles are then deployed from the tip of the catheter, piercing the mucosa of the prostatic urethra
High-intensity focused ultrasound
Intraurethral stents
keep the prostatic urethra patent.

21. Prostate Cancer

22. INCIDENCE & EPIDEMIOLOGY
Most common cancer
Second leading cause of cancer death
Risk factors:
age
Under 40: 1:10,000
40-59: 1 in 103
60-79: 1 in 8
diet
↑ (fat, meat)
↓ (low fat, fish, plant based, lycopene, omega 3 FA, vit. E, selenium)
Family history
Recurrent prostatitis
prostate cancer is lower in countries where people eat predominantly low-fat, plant based diet

23. PATHOLOGY 95% are Adenocarcinoma The other 5%
90%: Transitional Cell Carcinomas’
The remaining are small cell carcinomas or sarcomas
Cytologic characteristics: hyperchromatic, enlarged nuclei with predominant nucleoli .
Cytoplasm : abundant; N-C ratio not helful in dx

24. 60 to 70% (peripheral)
10-20% (transition)
5-10% (central)

25. PRESENT- Normal glands, BPH, precursor lesions (PIN)
BASAL LAYER
ABSENT – prostate CA
PRESENT- Normal glands, BPH, precursor lesions (PIN)
If diagnosis of prostate cancer is in question, HMW keratin immunohistochemical staining is used
Stains basal cells, prostate cancer is negative

26. Prostatic Intraepithelial Neoplasia and Atypical Small Acinar Proliferation (ASAP) are thought to be precursor lesions
Men found to have these lesions may be at an increased risk for developing prostate cancer

27. GLEASON GRADING SYSTEM
The Gleason score is obtained by adding the primary and secondary grades together
Gleason Grades ranges from 1 to 5
Gleason scores range from 2 to 10
Gleason Score of:
2-4: Well differentiated
5-6: Moderately Differentiated
8-10: Poorly differentiated

28. GLEASON GRADING SYSTEM
The most important difference between Gleason pattern 1 and 2 is the presence or absence of circumscription respectively.
The focus of cancer is not circumscribed. The glands are round to oval and uniformly placed. There are no sharply-angulated or distorted glands. 
Even at low magnification, one can easily appreciate the variation in size, shape, and spacing of glands. Many small glands have occluded or abortive lumens. There is no evidence of glandular fusion.

29. GLEASON GRADING SYSTEM
The glands are fused and there is no intervening stroma. Glandular fusion is a hallmark of Gleason grade 4.
Tumor cells are arranged in solid sheets with no attempts at gland formation.

30. TNM STAGING SYSTEM
Clinical staging system:
DRE and TRUS
NOT biopsy

31. Clinical Findings Symptoms Most early stage CaP are asymptomatic
Presence of symptoms suggests locally advanced or metastatic disease
Obstructive or irritative voiding: local growth of tumor
Bone pain: metastatic disease to the bones
Paresthesias and weakness of the LE: cord compression

32. Symptoms Difficulty voiding or urinary retention
Weak or interrupted flow of urine
Frequent urination (especially at night)
Pain or burning during urination.
Increased urinary frequency
Blood in urine
Back pain
Painful ejaculation

33. Clinical Findings B. Signs (Physical Exam)
Digital Rectal Exam (induration)
regional lymphadenopathy
specific signs of cord compression

34. Clinical Findings C. Laboratory Findings
Azotemia: bilateral ureteral obstruction (from direct extension into the trigone or from retroperitoneal adenopathy)
Anemia: metastatic disease
Alkaline phosphatase: elevated in bone metastases
Acid phosphatase: disease outside the confines of prostate

35. Clinical Findings D. Tumor Markers- Prostate Specific Antigen
PSA velocity
PSA density
Age-adjusted reference ranges for PSA
Racial variations in CaP detection
Molecular forms of PSA

36. Prostate Specific Antigen
PSA Velocity
Rate of change of serum PSA
Annual PSA velocity 0.75 ng/mL - increase risk of cancer, failure of treatment, and development of metastases
PSA velocity significant only when several PSA assays are carried out by the same lab over a period of at least 18 mos.
B. PSA Density
Ratio of PSA to gland volume
Elevated approx ng/mL/g of BPH tissue

37. Prostate Specific Antigen
C. Age-adjusted reference ranges for PSA
Rise in PSA with increasing age results from prostate gland growth BPH, higher incidence of subclinical prostatitis, growing prevalence of insignificant prostate cancers
Age (years)
PSA normal ranges (ng/mL)
40-49
0-2.5
50-59
0-3.5
60-69
0-4.5
70-79
0-6.5

38. Prostate Specific Antigen
D. Racial Variations in CaP detection
African-American: higher baseline, worst outcomes
E. Molecular Forms of PSA
2 forms: free and protein bound
90%- 1-antitrypsin, others - 2-macroglobulin

39. Clinical Findings E. Prostate Biopsy
Systematic sextant prostate biopsy
Most commonly employed technique used in detecting CaP
Obtained under TRUS guidance (apex, midsection, & the base of each side of the prostate at the midsagittal line halfway between the lateral border & midline of the gland)
To predict extracapsular extension & risk of relapse following radical prostatectomy

40. Systematic sextant prostate biopsy
Indications:
Men over age 40 with elevated PSA
Abnormal digital rectal examination (DRE)
Abnormal ultrasound of the prostate (TRUS)
Urinary symptoms without an obstructive etiology of symptoms

41. Clinical Findings F. Combined Modality Risk Assessment Risk Group
Criteria
Recurrence after therapy
Risk Lower
Risk Higher
Need for Routine Radiographic Imaging
Low
PSA <10, Gleason <6 and T1,T2a
6-20%
Gleason 2-4, <50% +biopsies, PSA <6
>50% + biopsies
None
Intermediate
PSA 10-20, Gleason 7 and/ T2b, T3a
26-60%
<50% +biopsies, PSA <15, Gleason 3/4
>50% + biopsies, Gleason 3/4
Bone scan for PSA >15
High
PSA >20, Gleason 8-10 and/ T3b
31-100%
PSA 10, T1/T2 disease
7113 variables
Bone scan, CT/MRI of pelvis

42. Imaging 1. TRUS Useful in performing prostatic biopsies
Providing local staging information if cancer is detected
Allows uniform spatial separation & sampling of the regions of the prostate & also makes lesion-directed biopsies possible
CaP appears as a hypoechoic lesion in the peripheral zone
Provides more accurate local staging than does DRE

43. TRUS

44. TRUS Sonographic criteria for extracapsular extension:
Bulging of the prostate contour or
Angulated appearance of the lateral margin
Sonographic criteria for seminal vesicle invasion:
Posterior bulge at the base of the seminal vesicle
Asymmetry in echogenicity of the seminal vesicle associated w/ hypoechoic areas at the base of the prostate

45. TRUS
Axial transrectal ultrasonographic (TRUS) scan shows extensive hypoechoic area (arrows) in the right peripheral zone.

46. TRUS
Enables measurement of the prostate volume (calculation of PSA density)
PSA density
= (π/6) X (AP diameter) X (transverse diameter) X sagittal diameter
Cryosurgery & brachytherapy

47. Imaging 2. Endorectal magnetic resonance imaging (MRI)
staging accuracy: 51 – 92%
high image quality
operator-dependent
expensive

48. Imaging 3. Axial Imaging (CT,MRI) Criteria: (-) bone scans
Selectively performed to exclude lymph node metastases in high risk patients who are thought to be candidates for definitive local therapy
Criteria:
(-) bone scans
T3 cancers or a PSA>20ng/mL
Primary Gleason grade 4 or 5 cancers

49. Imaging 4. Bone Scan Can be omitted in patients w/ Newly diagnosed,
Untreated prostate cancer who are asymptomatic
Have T1 and T2 disease
Serum PSA concentrations < 15 ng/mL

50. Imaging 5. Antibody Imaging
ProstaScint: mAb to an intracellular component of PSMA
SPECT images obtained 30mins to assess vasculature and at hours
Recognizes the intracellular domain of PSMA; only soft tissues are imaged and the test may suffer from both false + and -

51. Prostate CA Differential Diagnosis
Factors That Increase PSA
BPH
Urethral instrumentation
Infection
Prostatic infarction
Vigorous prostate massage
Causes of Induration of the prostate:
Chronic granulomatous prostatitis
Previous TURP or needle biopsy
Prostatic calculi

52. Prostate CA Differential Diagnosis
Paget’s Disease
Sclerotic Lesions on plain XRAY films
Elevated Alkaline Phosphatase
PSA levels usually normal
XRAY - subperiosteal cortical thickening
Paget's Disease (Osteitis Deformans)

53. Screening for CaP
PSA improves the detection of clinically important tumors
Most PSA detected tumors are curable
Mortality of prostate cancer is declining in areas where screening occurs
Screening consist of a combination of DRE and serum PSA

54. PSA

55. Treatment of Localized Disease

56. 1. General Considerations
Treatment decisions are based on the:
Grade and stage of the tumor
Life expectancy of the patient
Ability of therapy to ensure disease-free survival
Morbidity
Patient and physician preferences

57. 2. Watchful waiting
Therapeutic benefit of radical treatment for early stage prostate cancer has not yet been proven
Older prostate ca patients may have concomitant illnesses
Small, well-differentiated prostate cancer have very slow growth rates

58. 3. Radical prostatectomy
Understanding the anatomy of the pelvis resulted in lower rate of complications
Prognosis treated by radical prostatectomy correlates with the pathologic stage of the specimen
Patients with adverse prognostic factors undergoing surgery is decreasing-> established normograms based on serum PSA, clinical DRE stage, and Gleason sum derived from biopsy

59. 3. Radical protastectomy
Patients with organ confined CA disease free survival rate 70%-85% and 75% for those with extensive extracapsular extension
High grade tumors (Glial sum >7) have higher risk of progression
Morbidity – related to the experience of the surgeon

62. 3. Radical prostatectomy
Immediate intraoperative complications:
blood loss
rectal injury
ureteral injury
Perioperative complications:
deep venous thrombosis
pulmonary embolism
lymphocoele formation
wound infection
Late complications:
urinary incontinence
impotence
-blood loss (more common in retropubic approach) -rectal injury (rare with retropubic approach, common in perineal approach, can be repaired)
-ureteral injury (exceedingly rare.)

63. 4. Radiation therapy-external beam therapy
Standard XRT
Delivery of 6500 – 7000 cGy to the prostate
Depend upon bony landmarks to define treatment borders or a single CT slice to define target volume
Often fails to provide adequate coverage of the target volume
Improved with the use of 3D treatment planning software
Acute toxicity reduced with use of conformal radiotherapy

64. 4. Radiation therapy-external beam therapy
3 Dimensional conformal radiotherapy
ability to calculate dose in 3 dimensions
ability to generate 3 dimensional dose displays and dose volume histograms
less normal tissue is irradiated because of the use of multiple complex field
toxicity is reduced

65. 5. Radiation therapy-brachytherapy
Placing radioactive seeds under TRUS guidance
With computer software- can preplan a precise dose of radiotherapy to be delivered by TRUS guidance

66. 6. Cryosurgery Less invasive form for tx of localized CaP
Use of subfreezing tissue to destroy tissue
Freezing the prostate is carried out using a multiprobe cryosurgical device
Multiple hollow-core probes are placed percutaneously under TRUS guidance
In the short term, can result in negative post treatment prostatic biopsies and low or undetectable serum PSA levels

67. Treatment of Locally Advanced Disease
RADIOTHERAPY
Most patients with T3 CaP are treated with neoadjuvant hormonal therapy followed by XRT.
Superior to XRT alone

68. Treatment of Recurrent Disease

69. 1. Following Radical Prostatectomy
Site of Reccurrence established with:
Interval from surgery to the detectable PSA concetration
PSA doubling time
Selective Imaging studies
Recurrence is related to:
Cancer grade
Pathologic stage
Extent of extracapsular extension
Recurrence more common in:
Positive surgical margins
Positive extracapsular extension
Seminal vesicle invasion
High grade disease.

70. 1. Following Radical Prostatectomy
Systemic relapse
Persistently detectable PSA immediately after surgery
PSA levels detectable in the early postoperative period
PSA levels that double rapidly
Local recurrence
PSA levels undetectable initially then becoming detectable after a long time after radical protastectomy
PSA doubling time is prolonged

71. 2. Following Radiation Therapy
Rising PSA levels
Prostate Biopsy - identify local recurrence
Imaging with bone scans and CT - identify distant recurrence
Most patients are treated with Androgen Ablation Therapy
Patients with Local Recurrence – salvage radical prostatectomy or cryotherapy

72. Treatment of Metastatic Disease

73. 1. Initial endocrine therapy
Most prostatic carcinomas are hormone dependent.
Free testosterone -> enters prostate cell -> converted to DHT(major intracellular androgen) -> binds a cytoplasmic receptor protein -> complex moves to nucleus -> transcription
Androgen deprivation at several levels along the Pituitary – Gonadal Axis

75. 1. Initial endocrine therapy
LHRH agonist and orchiectomy - most common forms of primary androgen blockade used
Ketoconazole – rapid onset of action, used in advanced Prostate Ca presenting with spinal cord compression and DIC
Complete Androgen Blockade - Antiandrogen plus LHRH agonist or orchiectomy: suppresses both testicular and adrenal androgen (allows better initial and longer response)
Antiandrogen - competitively binding the receptor for DHT (responsible for prostatic growth and development)

76. 2. Early manipulations for endocrine therapy failure
Patients receiving complete androgen blockade therapy who demonstrate a rise in serum PSA levels must discontinue use of antiandrogen
PSA receiving monotherapy (LHRH agonist or orchiectomy whose PSA starts rising may respond to the addition of an antiandrogen

77. 3. Hormone Refractory Disease
Failure of Hormonal Therapy
Brisk and significant fall in PSA levels predictive of survival
Standard Chemotherapy agent
Estramustine/Taxane Combination
Second Line Chemotherapy
Mitoxantrone or Prednisone

78. BPH
PROSTATIC CANCER
PROSTATIC ZONE
TRANSITIONAL
PERIPHERAL
AGE PREDILECTION
INCREASES WITH AGING
RISK FACTORS
GENETICS,AGING
GENETICS, RACE, AGING, DIET
SYMPTOMS
OBSTRUCTIVE, IRRITATIVE
OBSTRUCTIVE, IRRITATIVE, BONE PAIN, CORD COMPRESSION SX
SIGNS (DRE)
SMOOTH, FIRM, ELASTIC, ENLARGED
INDURATION
OTHER SIGNS
REGIONAL LYMPHADENOPATHY, CORD COMPRESSION SIGNS
DIAGNOSIS
DRE
PROSTATE BIOPSY, (PSA- SCREENING ONLY)
TREATMENT
WATCHFUL WAITING, MEDICAL (ALPHA BLOCKER, 5- ALPHA REDUCTASE inhibitor )
SURGERY (TURP, OPEN, TUIP)
MINIMALLY INVASIVE TX
WATCHFUL WAITING/ACTIVE SURVEILLANCE
RADICAL PROSTATECTOMY
RADIOTHERAPY= EXT. / INT.
CRYOSURGERY
HIFU