PROSTATE TUMORS

1. 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 theprostate (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: 41-50 – 20%,51-60 – 50%, >80 – > 90% • clinical BPH (prostatic obstruction):55 – 25%, 75 – 50% • genetic predisposition: autosomaldominant – 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 smoothmuscle  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