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

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

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: 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

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

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

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

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

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

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

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

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

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

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)

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

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

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