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Urological Malignancies

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Urological Malignancies

Urological MalignanciesMr Rahul MistryUrology Special RegistrarMersey DeaneryIntroduction

TopicsProstate cancerTesticular cancerBladder cancer

Prostate CancerCommonest malignancy of male urogenital tract There are about 10,000 cases per year in the United Kingdom Rare before the age of 50 years Found at post-mortem in 80% of men older than 80 years 5-10% of operation for benign disease reveal unsuspected prostate cancer Prostate Anatomy

PathologyAdenocarcinomas Arise in the posterior / periphery Spread through capsule into perineural spaces, bladder neck, pelvic wall and rectum Lymphatic spread - common Haematogenous spread occurs to axial skeleton Graded by Gleason classificationRisk FactorsNot well knownFirst-line relative - risk is at least doubledIf two or more first-line relatives - the risk increases 5- to 11-fold

Incidence high in the USA and Northern Europe and low in South-East AsiaHowever, if Japanese men move from Japan to Hawaii, their risk of CaP increases, and if they move to California their risk increases even more and approaches that of American men

High content of animal fat in the diet may be important in increasing the risk of developing CaP

Low intakes of vitamin E, selenium, lignans and isoflavenoids (soybeans) Sunlight might be protective against CaP due to an increase in vitamin D levelsPresentation

Clinical features60% symptoms of bladder outflow obstruction 10% incidental findings at TURP Bone pain, cord compression or leuco-erythroblastic anaemia Renal failure can occur due to bilateral ureteric obstruction DiagnosisDRE: Hard noduleLoss of central sulcus Transrectal biopsyPelvic MRI - stagingBone scans metastasisUnlikely to be abnormal if asymptomatic and PSA < 10 ng/ml PSAProstate specific antigenKallikrein-like protein produced by prostatic epithelial cells

Age matched:40-50:2.550-60: 3.560-70: 4.570-80: 6.5

>10 ng/ml is highly suggestive of prostatic carcinoma Can be significantly raised in BPH, UTIs or secondary to retentionMonitoring response to treatment PSA value and risk of CaPPPV = positive predictive valuePSA ng/mLPPV for cancer0 - 12.8-5%1 - 2.510.5-14%2.5 - 422-30%4 - 1041%> 1069%The 15-year risk of dying from CaP in relation to Gleason score at diagnosis in patients with localized disease aged 55-74 yearsGleason scoreRisk of cancer deathCancer-specific mortality2 44 7%8%56 11%14%618 30%44%742 70%76%8 1060 87%93%Gleason scoreGrading scoreScore: 2 102 - least aggressive 10 -most aggressive.

Total score = the sum of the two most common patterns (grades 1-5) of tumour growth found

TRUS prostate biopsyTURPPrimary tumourTX Primary tumour cannot be assessedT0 No evidence of primary tumourT1 Clinically inapparent tumour not palpable or visible by imagingT1a Incidental histological finding in 5% or less of tissue resectedT1b Incidental histological finding in more than 5% of tissue resectedT1c Tumour identified by needle biopsy (e.g., because of elevated PSA)

T2 Tumour confined within the prostateT2a Tumour involves one half of one lobe or lessT2b Tumour involves more than half of one lobe, but not both lobesT2c Tumour involves both lobes

T3 Tumour extends through the prostatic capsuleT3a Extracapsular extension (unilateral or bilateral)T3b Tumour invades seminal vesicle(s)

T4 Tumour is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, or pelvic wallTreatmentMore men die with than from prostate cancer Treatment depends on stage of disease, patient's age and general fitness Local disease ObservationRadical radiotherapy / brachythrapyRadical prostatectomy Locally advanced disease Radical radiotherapy Hormonal therapy Metastatic diseaseHormonal therapyHormonal therapy80% of prostate cancers are androgen dependent for growth Hormonal therapy involves androgen depletion Produces good palliation until tumours 'escape' from hormonal control

Androgen depletion can be achieved by: Bilateral subcapsular orchidectomy LHRH agonists - goseraline (Zoladex)Anti-androgens - cyproterone acetate, bicalutamideComplete androgen blockade Oestrogens - stilbeostrol

Testosterone ProductionRegulated by the hypothalamic-pituitary-gonadal axis. LHRH stimulates the anterior pituitary to release LH and FSHLH stimulates the Leydig cells of the testes to secrete testosterone

In Prostate cells, testosterone is converted by the enzyme 5- -reductase into 5- -dihydrotestosterone (DHT), which is an androgenic stimulant approximately 10 times more powerful than the parent molecule

Circulating testosterone is peripherally aromatized and converted into oestrogens which, together with the circulating androgens, exert a negative feedback control on the hypothalamic LH secretion

If prostate cells are deprived of androgenic stimulation, they undergo apoptosis (programmed cell death)

Any treatment ultimately resulting in the suppression of androgen activity is referred to as androgen deprivation therapyTestosterone Production

Testicular tumoursCommonest solid malignancy in young men 1% - 1.5% of male neoplasms5% of urological tumours3-6 new cases occurring per 100,000 males per year in Western societyOnly 1-2% of cases are bilateralIncidence high in caucasians in northern Europe and USA 1400 new cases per year in UK 95% 5 year survival testis localised diseasePeak incidenceThird decade of life for non-seminomaFourth decade for pure seminomaEpidemiological risk factorsHistory of cryptorchidismx4-13 increased risk7-10% tumours in undecended testisKlinefelters syndromeFHxFather/brother: x6-8 increased riskPresence of a contralateral tumour5-10% riskHIVseminomaDiagnosisUnilateral testicular mass 20% scrotal pain 27% local pain TraumaReduction in testis sizeGynaecomastia 7% (beta HCG) more common in non-seminomatous tumours

Symptoms of metastatic diseaseSeminomas metastasize to para-aortic nodes back pain 11% Teratomas spread to para-aortic nodes, liver, lung, bone and brain

10% of cases can mimic an epididymo-orchitisSupraclavicular / distant metastasesPalpable abdominal massTumour markersStaging and response to treatment

Alpha-fetoproteinProduced by yolk sac elements Not produced by seminomas

Beta-human chorionic gonadotrophinProduced by trophoblastic elements Elevated levels seen in both teratomas and seminoma

Lactate DehydrogenaseLess specific markerConcentration is proportional to tumour volumeElevated in 80% of patients with advanced testicular cancer

It should be noted that negative markers levels do not exclude the diagnosis of a germ cell tumourInvestigationsUltrasound Sensitivity almost 100%: intra- or extratesticularInexpensive test Screening test of the contralateral testis in the follow-up

Elevated serum beta-hCG or AFP

MRI Higher sensitivity and specificity than ultrasoundMay differentiate seminomatous from non-seminomatous tumoursSensitivity of 100% and a specificity of 95-100%High cost

Thoraco-abdominal CT scanning for staging

TreatmentRadical OrchidectomySeminomas / TeratomasSeminomas are radiosensitiveTeratomas are not radiosensitiveSurgery: Inguinal orchidectomyRadiotherapyChemotherapyBladder carcinoma

Bladder carcinoma95% transitional cell carcinomas4% squamous / adenocarcinoma Superficial tumours are usually low grade and associated with a good prognosis Muscle invasive tumours are of higher grade and have a poorer prognosisPathologyTCCs should be regarded a 'field change' disease with a spectrum of aggression

80% of TCCs are superficial and well differentiated Only 20% progress to muscle invasion Associated with good prognosis

20% of TCCs are high-grade and muscle invasive 50% have muscle invasion at time of presentation Associated with poor prognosis

Aetiological factorsOccupational exposure 20% of TCC are believed to result from occupational factors Chemical implicated - aniline dyes, chlorinated hydrocarbons Cigarette smoking Pelvic irradiation - for carcinoma of the cervix Schistosoma haematobium associated with increased risk of squamous carcinomaPathological stagingRequires bladder muscle to be included in specimen

Staged according to depth of tumour invasion

Grade of tumour differentiation TisIn-situ disease TaEpithelium onlyT1Lamina propria invasionT2Superficial muscle invasionT3aDeep muscle invasionT3bPerivesical fat invasionT4Prostate or contiguous muscleG1Well differentiatedG2Moderately well differentiatedG3 Poorly differentiatedPresentation & Investigation80% present with painless haematuria Also present with treatment-resistant infection or bladder irritability and sterile pyuria

Haematuria clinic involves:Urinalysis Mid stream urine Serum urea and creatinine Ultrasound - bladder and kidneys KUB xray - to exclude urinary tract calcification Flexible cystoscopy Consider IVU / CT urography if no pathology identified

Tx of Superficial TCCRequires TURT follow-up Consider prophylactic chemotherapy (mitomycin-C) if risk factor for recurrence or invasion (e.g. high grade) Consider immunotherapy BCG = attenuated strain of Mycobacterium bovis Reduces risk of recurrence and progression 50-70% response rate recorded Occasionally associated with development of systemic mycobacterial infection


Carcinoma in-situCarcinoma-in-situ is an aggressive disease Often associated with positive cytology 50% patients progress to muscle invasion Consider immunotherapy - BCGIf fails patient may need radical cystectomy Invasive TCCChoices are between radical cystectomy and radiotherapy Radical cystectomy has an operative mortality of about 5%

Urinary diversion achieved by: Ileal conduit Neo-bladder

Local recurrence rates afte

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