Scope

• Anatomy •Urologic Malignancies • Trauma • Emergencies • Infections • Lower Urinary Tract Obstruction • Upper Urinary Tract Obstruction • Pediatric • Key Points Emmanuel L. Barcenas Urologist/Urologic Surgeon Urology Specialty Group and Associates

• Doctor of Medicine, SWU • Diplomate, Philippine Board of Surgery and the Philippine Board of Urology • Fellow, Philippine Urological Association • Fellow, Philippine College of Surgeons • Member, Philippine Endourological Society • Member, Phillippine Society of Urooncologists Urologic Malignancies Urologic Malignancies

•Bladder Cancer • •Kidney Cancer • Cancer Urothelial Tumors of the UB •Transitional cell epithelium lines the urinary tract from the renal pelvis, ureter, urinary bladder, and the proximal two-thirds of the urethra •Tobacco use is the most frequent risk factor (50% in men and 40% in women), followed by occupational exposure to various carcinogenic materials such as automobile exhaust or industrial solvents. Detection of Urothelial Cancer

•Painless gross hematuria occurs in 85% of patients & requires a complete evaluation that includes cystoscopy, urine cytology, CT scan, & a PSA. •Recurrent or significant hematuria (>3 RBC’s/HPF on 3 urinalysis, a single urinalysis with >100 RBCs, or gross Hematuria) is associated with significant renal or urologic lesion in 9.1% Detection of Urothelial Cancer

• Patients with microscopic hematuria require a full evaluation, but low-risk patients do not require repeat evaluations. • High-risk individuals primarily are those with a smoking history & should be evaluated every 6 months. • The level of suspicion for urogenital neoplasms in patients with isolated painless hematuria and nondysmorphic RBCs increases with age. • White light cystoscopy with random bladder biopsies is the gold standard for tumor detection

History & Staging

•Low-grade papillary lesions are likely to recur in up to 60% of patients but invade in less than 10% of cases. •High-grade lesions also recur; invasion & subsequent stage progression can occur in 50% of tumors. •Muscle-invasive bladder cancer leads to death in a significant proportion of patients despite aggressive therapy.

Pathology

•Malignant tumors are classified as low grade or high grade. •The most important risk factor for progression is grade. •Urothelial tumors exhibit polychronotropism, which is the tendency to recur over time in new locations in the urothelial tract. •As long as urothelium is present, continuous monitoring is required. •In the presence of a known bladder tumor, unilateral or bilateral hydronephrosis is an ominous sign of locally advanced disease (at least muscle-invasive bladder cancer) •Patients who have disease invading into bladder muscle (T2), immediate (within 3 months of diagnosis) cystectomy with extended lymph node dissection offers the best chance of survival

Non Muscle Invasive Bladder Ca

•Patients with non–muscle-invasive bladder cancer (confined to the bladder mucosa or submucosa) can be managed with TUR alone and adjuvant intravesical (instilled into the bladder) chemotherapy/immunotherapy •Intravesical treatments are advised for patients with diffuse ClS，recurrent disease ，>40% involvement of the bladder surface by tumor，or T1 disease Endoscopic Surgical Management

•TURBT is performed both to remove all visible tumors & to provide specimens for pathologic examination to determine stage & grade. •Repeat resection within 1 to 6 weeks is usually indicated in patients with high-grade disease. • Single-dose intravesical chemotherapy administered within 6 hours of resection reduces recurrence of low-risk tumors. •All suspicious lesions should be sampled, but “random” biopsies are not required in low-risk patients.

Immunotherapy

•Intravesical BCG has higher efficacy than intravesical chemotherapy. •BCG is the only agent shown to delay or reduce high-grade tumor progression. •Standard therapy, is Bacillus Calmette- Guérin (BCG) in six weekly instillations, followed by maintenance administrations for > 1 year •BCG is contraindicated in the setting of a disrupted urothelium because of the risk of intravasation & septic death. Intravesical Chemotherapy

•Intravesical chemotherapy has a clear impact on tumor recurrence when immediately instilled after TURBT & in the adjuvant setting •In general, side effects of chemotherapy tend to be less common & less severe than those for BCG, but BCG is more efficacious. •Because upper tract recurrence is fairly common (up to 17% of patients with carcinoma in situ), surveillance must be performed with RGPs or CT urograms. •Patients are monitored for recurrence at 3 month intervals during the first year. Surveillance & Prevention •Cystoscopy is the hallmark of surveillance. Usually every 3 months. •Increased fluids, smoking cessation, & a low-fat diet are recommended. Prevention •Stopping or never starting smoking is the best prevention for bladder cancer. •There are no clear dietary or micronutrient programs to prevent primary bladder cancer. •BCG plus high-dose vitamins may prevent recurrent bladder cancer. Muscle Invasive Bladder Cancers Neoadjuvant Chemotherapy

•Presurgical (or neoadjuvant) chemotherapy increases the cure rate by 5–15%, •In patients receiving three cycles of neoadjuvant MVAC followed by cystectomy had a significantly better median (6.2 yea rs) and 5-year surviva l (57%) compared to cystectomy alone (median survival 3.8 years; 5-year survival 42%).

•In men, the prostate is removed with the bladder (Radical Cysto ). •In women, the uterus, ovaries, and anterior wall of the vagina are removed with the bladder (Anterior Pelvic Exenteration). Partial Cystectomy

•Limited to patients with a solitary lesion in which radical cystectomy is otherwise contraindicated & a sufficient margin can be obtained. •Partial cystectomy can be curative in other tumor types including squamous cell carcinoma & adenocarcinoma. Partial Cystectomy

•Restricted to primary solitary lesions unsuitable for removal by transurethral resection and to residual tumor at repeat resection 2 months later. •The tumor must also lie at a site that allows 2 cm of normal tissue around it to be removed. •Bladder must have adequate capacity and compliance to be functional after removal of part of its wall. Radical Cystectomy

•Designed to remove the bladder, pelvic peritoneum, prostate, and in men and the urethra, uterus, broad ligaments, and anterior third of the vaginal wall in women. •In both sexes, pelvic lymphadenectomy is an integral part of the operation. •Some form of urinary diversion must be created. Radical Cystectomy

•The boundaries of dissection of a standard pelvic lymph node dissection are the genitofemoral nerve laterally, the internal iliac artery medially, Cooper ligament caudally, & the crossing of the ureter at the common iliac artery cranially. •Female patients with stage T1 or T2 bladder tumors that are distal to the bladder trigone are candidates for orthotopic neobladder construction.

•Orthotopic neobladder has emerged as a popular urinary diversion for patients without urethral involvement. •Most common diversion is noncontinent, the ileal conduit

Metastatic Disease

•Overall response rates of >50% have been reported using combinations such as methotrexate， vinblastine ， doxorubicin， and cisplatin (MVAC); gemcitabine and cisplatin (GC); or gemcitabine，paclitaxel， and cisplatin (GPC) MANAGEMENT OF BLADDER CANCER

Nature of Lesion Management Approach Non-muscle-invasive disease Endoscopic removal usually with intravesical therapy

Muscle-invasive disease Cystectomy 士 systemic chemotherapy (before or after surgery)

Metastatic disease Curative or palliative chemotherapy (based on prognostic factors) 士su rgery Testicular Tumors •Primary germ cell tumors (GCTs) of the testis arising by the malignant transformation of primordial germ cells constitute 95% of all testicular neoplasms •Testicular cancer is the most common solid malignancy in men age 15 to 35 years. •A painless testicular mass is pathognomonic for a testicular malignancy •A major risk for the development of testicular cancer is cryptorchidism. •Cryptorchidism is associated with a several- fold higher risk of GCT. •Abdominal cryptorchid testes are at a higher risk than inguinal cryptorchid testes. •An isochromosome of the short arm of chromosome 12 [i( 1 2p)] is pathognomonic for GCT Demographics

•Testicular cancer is the most common solid tumor in men between the ages of 20 and 35 years. •Careful history, physical examination, and serum tumor markers (hCG, AFP, and LDH) are helpful in establishing the correct diagnosis. •Scrotal ultrasonography is extremely accurate in identifying solid intratesticular lesions, with greater than 95% sensitivity and specificity.

Tumor Markers

•Initial studies must include tumor markers, including α-fetoprotein (AFP), β-human chorionic gonadotropin (BHCG), and lactate dehydrogenase (LDH). •Elevated tumor markers are found almost exclusively in non-seminomatous germ cell tumors •10% of patients with localized and 25% with metastatic seminomas will have a modest rise in β-human chorionic gonadotropin. Tumor Markers

•AFP concentration is increased only in patients with nonseminoma GCT. •The presence of an increased AFP level in a patient whose tumor shows only , the patient should be treated for nonseminomatous GCT •LDH levels are less specific than AFP or hCG but are increased in 50-60% patients with metastatic nonseminoma and in up to 80% of patients with advanced seminoma. Tumor Markers

• AFP， hCG， and LDH levels should be determined before and after . • Increased serum AFP and hCG concentrations decay according to first -order kinetiιs; the half-life is 24- 36 h for hCG and 5-7 days for AFP. • AFP and hCG should be assayed serially during and after treatment. • The reappearance of hCG and/or AFP or the failure of these markers to decline according to the predicted half-life is an indicator of persistent or recurrent tumor. Radical Inguinal Orchiectomy

•Patients suspected of having a testicular neoplasm should undergo a radical inguinal orchiectomy with removal of the tumor-bearing testis and to the level of the internal inguinal ring. •A trans scrotal orchiectomy or biopsy is contraindicated

Radical Inguinal Orchiectomy •Radical orchiectomy establishes the histologic diagnosis and primary T stage, provides important prognostic information from the tumor histology, and is curative in 80% to 85% and 70% to 80% of CS I seminoma and CS I NSGCT

•After orchiectomy, a computed tomography (CT) scan of the chest，abdomen，and pelvis is generally performed Clinical Staging

• Testicular GCT follows a predictable pattern of spread from the primary tumor to retroperitoneal lymph nodes & then to distant metastatic sites. • The primary “landing zone” for left-sided tumors is the paraaortic & left renal hilar lymph nodes, & for right-sided tumors it is the interaortocaval & paracaval lymph nodes. • Chest radiography & CT are acceptable staging modalities in the absence of retroperitoneal lymphadenopathy or elevated serum tumor marker levels.

Non Seminomatous GCT

•Over 80% of patients with clinical stage IA nonseminoma are cured with orchiectomy alone and there is no survival advantage to RPLND (or adjuvant chemotherapy)，surveillance is the preferred treatment option. •Patients with limited, ipsilateral retroperitoneal adenopathy <2cm in largest diameter and normal levels of AFP and hCG can be treated with either a modified bilateral nerve-sparing RPLND or chemotherapy Seminoma

• Inguinal orchiectomy followed by immediate retroperitoneal radiation therapy or surveillance with treatment at relapse both result in cure in nearly 100% of patients with stage 1 seminoma • Generally， nonbulky retroperitoneal disease (stage IIA and small IIB) is treated with retroperitoneal radiation therapy. • Approximately 90% of patients achieve relapse-free survival with retroperitoneal masses < 3 cm in diameter • In bulkier disease， initial chemotherapy is preferred for all stage IIC and some stage II B patients GCT

•Regardless of histology， all patients with stage IIC and stage III and most with stage IIB GCT are treated with chemotherapy. •Combination chemotherapy programs based on cisplatin at doses of 100 mg/m2 plus etoposide at doses of 500 mg/m2 per cycle cure 70-80% of such patients， with or without bleomycin Malignant Tumors of the Kidneys Renal Cell Carcinoma

•Renal cell carcinoma (RCC) is a malignancy of the renal epithelium that can arise from any component of the nephron •Notable features include resistance to cytotoxic agents，infrequent responses to biologic response modifiers such as interleukin (IL) 2， robust activity to antiangiogenesis targeted agents，and a variable clinical course for patients with metastatic disease，including anecdotal reports of spontaneous regression. Renal Cell Carcinoma

•Renal tumors are usually solid, but they also can be cystic •Many environmental factors have been investigated as possible contributing causes; the strongest association is with cigarette smoking

•The most common sites of metastasis are the retroperitoneal lymph nodes and lungs, but liver, bone, and brain also are common sites of spread •Patients should undergo testing for the presence of metastatic disease including chest CT, bone scan, and liver function tests. Bosniak Classification System •The Bosniak classification system, based on septations, calcifications, and enhancement, is used to assess the likelihood of malignancy in Renal Cysts The Bosniak Classification System •Category I lesions are uncomplicated, simple, benign cysts of the kidney that are straightforward to diagnose on ultrasonography, CT, or MRI. No treatment is necessary. The Bosniak Classification System •Category II lesions are minimally complex cysts that are generally benign but have some radiologic findings that cause concern. These lesions include septated cysts, cysts with calcium in the wall or septum, infected cysts, & hyperdense (high-density) cysts. This category has now been subdivided to differentiate category II lesions that do not require surveillance from category IIF lesions that mandate surveillance. The risk of malignancy for category IIF renal cysts is 5% to 10%, & these lesions should be observed with periodic renal imaging.

The Bosniak Classification System •Category III lesions are more complex renal cysts that cannot be confidently distinguished from malignant neoplasms. The radiographic features include thickened irregular or smooth walls or septa in which measurable enhancement can be observed. Surgical exploration is usually indicated in healthy patients. About 50% of these lesions are malignant; the remainder prove to be benign multiloculated, hemorrhagic, or densely calcified cysts.

The Bosniak Classification System •Category IV lesions have large cystic components; irregular, shaggy margins; &, most important, solid enhancing portions that provide a definitive diagnosis of malignancy. Category IV lesions are almost invariably cystic RCCs that, if localized, require surgical treatment.

Renal Cell Carcinoma

•Hematuria, Abdominal pain or flank mass •Widespread use of radiologic cross-sectional imaging procedures (CT, ultrasound, MRI) contributes to earlier detection, including incidental renal masses detected during evaluation for other medical conditions. •Standard evaluation of patients with suspected renal cell tumors includes a CT scan of the abdomen and pelvis, chest radiograph, urine analysis, and urine cytology Radiologic Evaluation of Renal Mass •A dedicated (thin-slice) renal CT scan remains the single most important radiographic test for delineating the nature of a renal mass. •CT Urography is necessary to take full advantage of the contrast enhancement characteristics of highly vascular renal parenchymal tumors •Any renal mass that enhances with intravenous administration of contrast material on CT by more than 15 Hounsfield units (HU) should be considered an RCC until proved otherwise

Pathology

• Most sporadic RCCs are unilateral and unifocal. • Bilateral involvement can be synchronous or asynchronous and is found in 2% to 4% of sporadic RCCs, more common in patients with von Hippel- Lindau disease. • Multicentricity, which is found in 10% to 20% of cases, is more common in association with papillary histology and familial RCC • Clear cell RCC accounts for 70% to 80% of all RCCs, arise from the epithelial cells of the proximal tubules and usually show chromosome 3p deletions Classification of Epithelial Neoplasms Arising from the Kidney Carcinoma Type Growth Pattern Cell of Origin Cytogenetics

Clear cell Acinar or Proximal tubule 3p-, 5q+, 14q- sarcomatoid

Papillary Papillary or Proximal tubule +7, +17, -Y sarcomatoid

Chromophobe Solid, tubular, Distal tubules/cortical Whole arm losses or sarcomatoid collecting duct (1, 2, 6, 10, 13, 17, and 21)

Oncocytic Tumor nests Cortical collecting Undetermined duct

Collecting duct Papillary or Medullary collecting Undetermined sarcomatoid duct

Staging

•Abnormal liver function test results, elevated serum alkaline phosphatase or lactate dehydrogenase level or sedimentation rate, hypercalcemia, and significant anemia point to the probability of advanced disease. •The radiographic staging of RCC can be accomplished in most cases with a high- quality abdominal CT scan and a routine chest radiograph

Partial Nephrectomy

•Nephron sparing surgery should be considered in all patients, as those patients undergoing a radical nephrectomy are at risk for future chronic kidney disease •the risk of contralateral RCC is 2% to 3% in most series, •a partial nephrectomy may prevent the future need for dialysis in case of a contralateral kidney tumor Partial Nephrectomy

•Situations in which RN would render the patient anephric or at high risk for ultimate need of dialysis bilateral synchronous RCC, to preserve as much functioning renal tissue as possible •A functioning renal remnant of at least 20% of one kidney is necessary to avoid end-stage renal failure •Local recurrence after PN ranged from 3% to 5%, Partial Nephrectomy

•PN is now standard of care for the management of clinical T1 renal masses in the presence of a normal contralateral kidney •Patients who undergo nephron-sparing surgery for RCC may be left with a relatively small amount of renal tissue and are at risk for development of long-term renal functional impairment from hyperfiltration renal injury

•Ablative techniques such as cryoablation and radiofrequency ablation are also popular choices, especially among those who are poor surgical candidates

Radical Nephrectomy

•RN encompasses early ligation of the renal artery and vein, removal of the kidney with primary dissection external to the Gerota fascia, excision of the ipsilateral adrenal gland, and performance of a complete regional lymphadenectomy from the crus of the diaphragm to the aortic bifurcation

Radical Nephrectomy

•For large tumors, particularly on the right side where the liver makes exposure of the tumor more difficult, a thoracoabdominal approach is very helpful

•Up to 10% of RCC invades the lumen of the renal vein or vena cava. •Thrombus below the level of the liver can be managed with cross-clamping above and below the thrombus and extraction from a cavotomy at the insertion of the renal vein •For thrombus above the hepatic veins, a multidisciplinary approach with either venovenous or cardiopulmonary bypass is necessary

Palliative Surgery in Advanced Renal Cell Carcinoma •In patients with advanced RCC, cytoreductive nephrectomy may help alleviate symptoms related to the primary tumor (e.g., intractable pain, hematuria) or paraneoplastic manifestations. •Resection of metastatic lesions (often in combination with radiation or systemic therapy) is sometimes performed for relief of symptoms or to prevent life-threatening or disabling sequelae. Advanced Renal Cell Carcinoma • Metastatic renal cell carcinoma is refractory to chemotherapy • Cytokine therapy with IL-2 or interferon α (IFN-α) produces regression in 10-20% of patients • Antiangiogenic therapy – Sunitinib, Pazopanib and axitinib as first line therapy; • Temsirolimus and everolimus, show activity in patients with untreated poor prognosis tumors and insunitinib/sorafenib-refractory tumors. Prostate Cancer •1 in 6 men will eventually be diagnosed with the disease, •Prostate Cancer remains the second leading cause of cancer deaths in men, •only 1 man in 30 with prostate cancer will die of his disease. •Current estimates are that 40% of early-onset and 5–10% of all prostate cancers are hereditary •African-American males have both a higher incidence of prostate cancer and larger tumors and more worrisome histologic features than white males Current Recommendations

• The need to pursue a diagnosis of prostate cancer is based on symptoms，an abnormal DRE or, more typically， a change in or an elevated serum PSA • The AUA has advised for screening for men 55 to 69 years of age. • Patients of African American descent or those with a family history of prostate cancer should be considered for screening at an earlier age (as early as 40). • Men with abnormal DRE or PSA elevation have an indication for to determine the presence of the disease Diagnostic Modalities

•Digital Rectal examination •Prostate Specific Antigen •PSA Derivatives and Molecular Forms •Volume-Based PSA Parameters. •Prostate-Specific Antigen Velocity. •Free Prostate-Specific Antigen Digital Rectal Examination

• Cancers 0ccur in the peripheral zone and may be palpated on DRE • Carcinomas are characteristically hard, nodular，and irregular. 20-25% of men with an abnormal DRE have cancer • Risk of prostate cancer among men with abnormalities on DRE - use PSA and DRE together for prostate cancer detection • PSA improves the positive predictive value of DRE for cancer when DRE and PSA are used in prostate cancer screening, detection rates are higher with PSA than with DRE and highest with both tests together

PSA

•The presence of prostate disease (prostate cancer, benign prostatic hyperplasia [BPH], and prostatitis) is the most important factor affecting serum PSA levels. •PSA is produced by both nonmalignant and malignant epithelial cells and, is prostate- specific，not prostate cancer-specific. •The level of PSA in blood is strongly associated with the risk and outcome of prostate cancer PSA

• Use of PSA increases the detection of prostate cancers that are more likely to be organ-confined when compared with detection without PSA • Future risk of prostate cancer and the chance of finding cancer on a prostate biopsy increase incrementally with the serum PSA level • AUA recommends shared decision making considering PSA based screening for men age 55-69. Outside this age range， PSA-based screening as a routine test was not recommended based on the available evidence. Key Points: PSA

• Most prostate cancer arises as clinically nonpalpable (stage T1c) disease with PSA between 2.5 & 10 ng/mL • The serum half-life of PSA, calculated after removal of all prostate tissue, is 2 to 3 days. • Finasteride (5 mg) & other 5α-reductase inhibitors used for treatment of BPH have been shown to lower PSA levels by an average of 50%. • The role for %fPSA is more applicable to PSA levels less than 10 ng/mL because the positive predictive rate of total PSA greater than 10 to 20 ng/mL has been demonstrated to be as high as 80%. Key Points

•The combination of DRE & serum PSA is the most useful first-line test for assessing the risk that prostate cancer is present. •The presence of prostate disease (prostate cancer, BPH, & prostatitis) is the most important factor affecting serum levels of PSA. •PSA increases detection rates of prostate cancer & leads to the detection of prostate cancers that are more likely to be confined • Direct visualization by transrectal ultrasound (TRUS) or magnetic resonance imaging (MRI) assures that all areas of the gland are sampled • Contemporary schemas advise an extended pattern 12-core biopsy that includes sampling from the peripheral zone as well as a lesion-directed palpable nodule or suspicious image guided sampling. • Men with an abnormal PSA and negative biopsy are advised to undergo a repeat biopsy.

•Prostate cancer is graded according to the Gleason scoring system. A primary and secondary score are assigned based on the most common and second most common histologic patterns. •Gleason score, preoperative PSA level, and digital rectal exam are used to estimate the likelihood of whether the cancer is localized, locally advanced, or metastatic. •Prostate cancer with a high Gleason score (8 to 10) or a high PSA level (>20) is much more likely to have spread, often at a micrometastatic level

Staging •Most common site of spread of prostate cancer is the pelvic lymph nodes and bone. •Radionuclide bone scans (bone scintigraphy) are used to evaluate spread to osseous sites •This test is sensitive but relatively nonspecific because areas of increased uptake are not always related to metastatic disease •True-positive bone scans are uncommon when the PSA is < 1 0 ng/mL unless the tumor is high grade Staging • TRUS is the imaging technique most frequently used to assess the primarγ tumor, but its chief use is directing prostate biopsies • MRI performed with an endorectal coil is superior to CT to detect cancer in the prostate and to assess local disease extent. • T 1 -weighted MRI produces a high signal in the periprostatic fat， periprostatic venous plexus， perivesicular tissues，lymph nodes， and bone marrow. • T2-weighted MRI demonstrates the internal architecture of the prostate and seminal vesicles. • MRI is also useful for the planning of surgery and radiation therapy.

•Multiple treatment options includes radical prostatectomy (retropubic, perineal, or robotic-assisted laparoscopic approaches), brachytherapy, and external-beam radiation therapy •For high-risk disease, either non–nerve- sparing surgery or external-beam radiation therapy plus androgen deprivation may be performed •Active surveillance has emerged as a safe and viable option for men with anticipated survival of <10 years, low Gleason score (6), early-stage disease (cT1c), and small volume disease as determined by biopsy. •Patients should be monitored closely with digital rectal exam, PSA testing, and repeat biopsy at 1 to 2 years to assess the possible progression of disease. Key Points: Conservative Management •Reserved for men with a life expectancy of less than 10 years & a low-grade prostate cancer. •Patients with clinically localized prostate cancer managed with watchful waiting have significantly higher rates of local cancer progression, metastases, & death from prostate cancer than do those treated initially with radical prostatectomy Radical Prostatectomy

•Radical prostatectomy, still remains the gold standard because of the realization that hormone therapy and chemotherapy are never curative, and not all cancer cells can be eradicated consistently by radiation or other physical forms of energy, even if the tumor is contained within the prostate gland. Radical Prostatectomy

•The main advantage of radical prostatectomy is that it offers the possibility of cure with minimal collateral damage to surrounding tissues. •It provide a more accurate tumor staging by pathologic examination of the surgical specimen. •Treatment failure is more readily identified. Radical Prostatectomy

• Disadvantages are the necessary hospitalization and recovery period; a possibility of incomplete tumor resection, if the operation is not performed properly or if the tumor is not contained within the prostate gland; and a risk for erectile dysfunction and urinary incontinence. • After radical surgery，PSA should become undetectable in the blood within 6 weeks. • PSA remains or becomes detectable after radical prostatectomy, the patient is considered to have persistent disease. PSA failure is usually defined as a value greater than 0.1 or 0.2 ng/mL

Radiation Therapy

•External beam radiotherapy uses gamma radiation beams directed at the prostate & surrounding tissues through multiple fields. •Patients with a high PSA level, high Gleason score, or large-volume tumor benefit from androgen-deprivation therapy in conjunction with radiotherapy. Radiation Therapy

•Cancer control after radiation therapy has been defined by various criteria， including a decline in PSA to <0.5 o r 1 ng/m L, or “non rising” PSA values, and a negative biopsy of the prostate 2 years after completion of treatment. •The current standard definition of biochemical failure (the Phoenix definition) is a rise in PSA by >2 ng/mL higher than the lowest PSA achieved

Radiation Therapy

•With brachytherapy, radioactive seeds or needles are implanted directly into the prostate gland to deliver a high dose of radiation to the tumor while possibly sparing the bladder & the rectum. •Adjuvant radiotherapy shortly after surgery is most likely to benefit patients with positive surgical margins or extracapsular tumor extension without seminal vesicle invasion or lymph node involvement.

Primary Hormone Therapy

• Primary androgen-deprivation therapy may be appropriate for older men, those with significant medical comorbidities precluding the use of curative therapy, & those who do not wish to undergo curative therapy. • Hormone therapy is never curative • Bilateral orchiectomy or luteinizing hormone– releasing hormone analogs. • Antiandrogens produce less sexual dysfunction & osteoporosis but have a greater risk for adverse cardiovascular complications. Cryoablation

•Uses argon gas circulating through hollow needles to freeze the prostate and helium gas to warm the urethra. •Cryoablation has been used as primary treatment for salvage after radical prostatectomy or radiotherapy FIGURE 1 THE TRANSRECTAL ULTRASOUND MOUNTED IN A STEPPER WHICH WOULD BE ATTACHED TO THE OPERATING ROOM TABLE DURING A CLINICAL PROCEDURE.CRYOPROBES ARE PLACED THROUGH THE GRID.

High-Intensity Focused Ultrasound (HIFU) •Acoustic energy can be used with ultrasound focusing to generate heat within the prostate gland, thus ablating focal lesions or the entire gland. •Treatment is performed under general or spinal anesthesia and takes 1 to 4 hours, depending on the prostate volume, which should not exceed 40 cc. Prevention

• Prostate Cancer Prevention Trial (PCPT), 5ARI finasteride, showed a 25% (95% confidence interval 19–31%) reduction in prevalence of prostate cancer • Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, a 23% reduction in the 4-year period prevalence was observed (p = .001). • Selenium and Vitamin E Cancer Prevention Trial (SELECT), which enrolled African-American men age ≥50 years and others age ≥55 years, showed no difference in cancer incidence in patients