1. DEPARTMENT OF UROLOGY IAŞI – 2013
PROSTATE TUMORS
DEPARTMENT OF UROLOGY IAŞI – 2013

2. PROSTATE TUMORS
prostate gland – the male organ most commonly afflicted with benign (BPH) or malignant (CaP) neoplasms
zonal anatomy of the prostate (McNeal, 1988)
peripheral zone (70%) – 60-70% CaP
central zone (25%) – 5-10% CaP
transition zone (5%) – 10-20% CaP, BPH

3. BPH INCIDENCE & EPIDEMIOLOGY most common benign tumor in men
incidence – age-related
histologic BPH: – 20%, – 50%, > 80 – > 90%
clinical BPH (prostatic obstruction): 55 – 25%, 75 – 50%
genetic predisposition: autosomal dominant – first-degree relatives (4×)
racial differences ?
ETIOLOGY
multifactorial and endocrine controlled
levels of free testosterone and estrogen  volume of BPH
aging   estrogen levels  induction of the androgen receptor  sensitization of the prostate to free testosterone

4. BPH PATHOLOGY transition zone – hyperplasia histologic components
stroma – collagen and smooth muscle  alpha-blockers
epithelium  reductase inhibitors
formation of ‘surgical capsule’
PATHOPHYSIOLOGY
obstructive component (prostate) + secondary response to outlet resistance (bladder)  symptoms of BPH

5. BPH obstructive component (prostate)
mechanical – intrusion into the urethral lumen or bladder neck (median lobe !)
dynamic – smooth muscle, rich in adrenergic nerve supply; autonomic stimulation  tone to the prostatic urethra
secondary response (bladder)  detrusor muscle hypertrophy and hyperplasia + collagen deposition   bladder compliance, detrusor instability  irritative voiding complaints
CLINICAL FINDINGS
Symptoms
obstructive
irritative
IPSS

6. BPH Signs physical examination
DRE – size and consistency of the prostate – smooth, firm, elastic enlargement of the prostate
focused neurologic examination
Laboratory Findings
urinalysis, serum creatinine, serum PSA
Imaging US
IVU – only with concomitant urinary tract disease or complications from BPH (hematuria, history of stone disease)
Cystometrograms and urodynamic profiles

7. BPH Differential Diagnosis
urethral stricture, bladder neck contracture, bladder stone, CaP, urinary tract infection, carcinoma of the bladder, neurogenic bladder disorders (neurologic disease, stroke, diabetes mellitus, back injury)
Treatment
watchful waiting
medical therapy
alpha blockers
5α-reductase inhibitors
phytotherapy

8. BPH conventional surgical therapy
transurethral resection of the prostate (TURP)
transurethral incision of the prostate (TUIP)
open simple prostatectomy
minimally invasive therapy
laser therapy
transurethral electrovaporization of the prostate
hyperthermia
transurethral needle ablation of the prostate
high-intensity focused ultrasound
intraurethral stents
transurethral balloon dilation of the prostate

9. PROSTATE CANCER
the most common cancer diagnosed and the second leading cause of cancer death in men
risk factors
increasing age
race
family history of CaP
high dietary fat intake
exposure to cadmium (cigarette smoke, alkaline batteries, welding industry)
Etiology
gene for familial CaP – chromosome 1
suppressor genes – chromosomes 8p, 10q, 13q, 16q, 17p, 18q

10. PROSTATE CANCER
epithelial-stromal interactions under the influence of growth factors (transforming growth factor-β, platelet-derived growth factor and neuroendocrine peptides) modulate prostate cell development, differentiation and metastasis
Pathology
adenocarcinoma (95%)
Grading & Staging
grade (1-5)
Gleason score (2-10) = primary grade + secondary grade
TNM staging system: T1a – ≤ 5% of tissue (TURP) has cancer, T1b – > 5% of tissue (TURP) has cancer, T1c – elevated PSA alone, T2a – tumor palpable by DRE or visible by TRUS on one side, confined to prostate, T2b – tumor palpable by DRE or visible by TRUS on both sides, confined to prostate

11. PROSTATE CANCER
T3a – extracapsular extension, T3b – seminal vesicle involvement, T4 – extention into bladder neck, sphincter, rectum, levator muscles or into pelvic sidewall
N1 – metastasis in a regional lymph node or nodes (obturator, internal iliac, external iliac and presacral); M1a – distant metastasis in nonregional lymph nodes, M1b – distant metastasis to bone, M1c – distant metastasis to other sites
Patterns of Progression
risk of extracapsular extension, seminal vesicle invasion and distant metastases raises with increasing tumor volume and more poorly differentiated cancers
locally advanced CaP may invade the bladder trigone  ureteral obstruction

12. PROSTATE CANCER
distant metastases – bones (lumbar spine, proximal femur, pelvis, thoracic spine, ribs, sternum, skul and humerus)  pathologic fractures, cord compression; lesions are typically osteoblastic
visceral metastases – lung, liver and adrenal gland
Clinical Findings
most patients with early-stage CaP are asymptomatic; presence of symptoms often suggests locally advanced or metastatic disease
local growth into the urethra or bladder neck or direct extension into the trigone  obstructive or irritative voiding complaints
metastatic disease  bone pain and symptoms of cord compression (paresthesias and weakness of the lower extremities, urinary or fecal incontinence)
DRE – induration

13. PROSTATE CANCER
bulky regional lymphadenopathy  lymphedema of the lower extremities
Investigations
bilateral ureteral obstruction  azotemia
bone metastases  elevated alkaline phosphatase
disease outside the prostate  raised serum acid phosphatase
serum PSA has increased the ability to detect CaP; other factors (BPH, urethral instrumentation and infection)  PSA
PSA velocity – increases > 0.75 ng/mL/y
PSA density – prostate biopsy if > 0.1 or 0.15
free-to-total PSA ratio < 25% would detect 95% of cancers, because prostate cancer patients demonstrate a lower percentage of free PSA (not protein-bound)

14. PROSTATE CANCER
systematic sextant prostatic biopsy – under TRUS guidance
TRUS – useful in performing prostatic biopsies and in local staging information – hypoechoic lesion in the peripheral zone
CT and MRI of the pelvis – exclude lymph node metastases in high-risk patients who are thought to be candidates for definitive local therapy (surgery or irradiation); cases identified as having lymphadenopathy may undergo CT-guided fine-needle aspiration; if lymph node metastases are confirmed, such patients may be candidates for alternative treatment regimens
the risk of disemination, in clinically localized prostate cancer, can be quantified, on the basis of serum PSA, tumor stage and grade (nomograms and probability curves) – Partin tables
bone scan can be excluded on the basis of serum PSA

15. PROSTATE CANCER Differential Diagnosis
 serum PSA – BPH, urethral instrumentation, infection, prostatic infarction, prostate massage or even DRE
induration of the prostate – chronic granulomatous prostatitis, prostatic calculi, previous TURP or needle biopsy
sclerotic lesions on plain x-ray films and  alkaline phosphatase – Paget disease (normal PSA, subperiosteal cortical thickening)
Treatment
localized disease
watchful waiting
radical prostatectomy
external beam radiotherapy
brachytherapy

16. PROSTATE CANCER locally advanced disease (T3)
neoadjuvant hormonal therapy followed by XRT
recurrent disease
following radical prostatectomy  radiation therapy (documented, isolated local recurrence)
following radiation therapy  androgen ablation therapy; only local recurrence  salvage radical prostatectomy
metastatic disease – androgen deprivation
primary androgen blockade – LHRH agonists (Goserelin, Leuprolide) or orchiectomy
estrogens (diethylstilbestrol)
complete androgen blockade – antiandrogen (Ketoconazole, Aminoglutethimide, Bicalutamide, Flutamide, Nilutamide) + LHRH agonist or orchiectomy