Mr Rahul MistryUrology Special Registrar

Mersey Deanery

Prostate cancer Testicular cancer Bladder cancer

Commonest 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

Adenocarcinomas 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 classification

Not well known First-line relative - risk is at least doubled If 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 Asia

However, 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 levels

60% 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

DRE: Hard nodule Loss of central sulcus

Transrectal biopsy Pelvic MRI - staging Bone scans – metastasis

Unlikely to be abnormal if asymptomatic and PSA < 10 ng/ml

Prostate specific antigen Kallikrein-like protein produced by prostatic epithelial cells

Age matched: 40-50:2.5 50-60: 3.5 60-70: 4.5 70-80: 6.5

>10 ng/ml is highly suggestive of prostatic carcinoma Can be significantly raised in BPH, UTI’s or secondary to

retention Monitoring response to treatment

PPV = positive predictive value

PSA ng/mL PPV for cancer

0 - 1 2.8-5%

1 - 2.5 10.5-14%

2.5 - 4 22-30%

4 - 10 41%

> 10 69%

Gleason score Risk of cancer death Cancer-specific mortality

2 – 4 4 – 7% 8%

5 6 – 11% 14%

6 18 – 30% 44%

7 42 – 70% 76%

8 – 10 60 – 87% 93%

Grading score Score: 2 – 10 2 - least aggressive 10 -most aggressive.

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

TRUS prostate biopsy TURP

TX Primary tumour cannot be assessed T0 No evidence of primary tumour T1 Clinically inapparent tumour not palpable or visible by imaging T1a Incidental histological finding in 5% or less of tissue resected T1b Incidental histological finding in more than 5% of tissue resected T1c Tumour identified by needle biopsy (e.g., because of elevated PSA)

T2 Tumour confined within the prostate T2a Tumour involves one half of one lobe or less T2b Tumour involves more than half of one lobe, but not both lobes T2c Tumour involves both lobes

T3 Tumour extends through the prostatic capsule T3a 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 wall

More men die with than from prostate cancer Treatment depends on stage of disease, patient's age

and general fitness Local disease –

Observation

Radical radiotherapy / brachythrapy

Radical prostatectomy Locally advanced disease

Radical radiotherapy

Hormonal therapy Metastatic disease

Hormonal therapy

80% 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, bicalutamide

Complete androgen blockade

Oestrogens - stilbeostrol

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

In Prostate cells, testosterone is converted by the enzyme 5-α -reductase into 5-α -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 therapy

Commonest solid malignancy in young men 1% - 1.5% of male neoplasms 5% of urological tumours 3-6 new cases occurring per 100,000 males per year

in Western society Only 1-2% of cases are bilateral Incidence high in caucasians in northern Europe and

USA 1400 new cases per year in UK 95% 5 year survival testis localised disease Peak incidence

Third decade of life for non-seminoma Fourth decade for pure seminoma

History of cryptorchidism x4-13 increased risk 7-10% tumours in undecended testis

Klinefelter’s syndrome FHx

Father/brother: x6-8 increased risk Presence of a contralateral tumour

5-10% risk HIV

seminoma

Unilateral testicular mass 20% scrotal pain 27% local pain Trauma Reduction in testis size Gynaecomastia 7% (beta HCG) more common in non-

seminomatous tumours

Symptoms of metastatic disease Seminomas 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-orchitis Supraclavicular / distant metastases Palpable abdominal mass

Staging and response to treatment

Alpha-fetoprotein Produced by yolk sac elements Not produced by seminomas

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

Lactate Dehydrogenase Less specific marker Concentration is proportional to tumour volume Elevated 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 tumour

Ultrasound Sensitivity almost 100%: intra- or extratesticular Inexpensive test Screening test of the contralateral testis in the follow-up

Elevated serum beta-hCG or AFP

MRI Higher sensitivity and specificity than ultrasound May differentiate seminomatous from non-seminomatous tumours Sensitivity of 100% and a specificity of 95-100% High cost

Thoraco-abdominal CT scanning for staging

Radical Orchidectomy

Seminomas are radiosensitive Teratomas are not radiosensitive Surgery: Inguinal orchidectomy Radiotherapy Chemotherapy

95% transitional cell carcinomas 4% 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 prognosis

TCCs 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

Occupational 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 carcinoma

Requires bladder muscle to be included in specimen

Staged according to depth of tumour invasion

Grade of tumour differentiation

Tis In-situ disease

Ta Epithelium only

T1 Lamina propria invasion

T2 Superficial muscle invasion

T3a Deep muscle invasion

T3b Perivesical fat invasion

T4 Prostate or contiguous muscle

G1 Well differentiated

G2 Moderately well differentiated

G3 Poorly differentiated

80% 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

Requires 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-situ is an aggressive disease Often associated with positive cytology 50% patients progress to muscle invasion Consider immunotherapy - BCG If fails patient may need radical cystectomy

Choices 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 after surgery are approximately 15% and after radiotherapy alone 50%

Pre-operative radiotherapy is no better than surgery alone

Adjuvant chemotherapy may have a role

Prostate_Exam.pps

Prostate cancer is a disease that can affect men as they

older. The sooner it’s detected, the better the prognosis.

UrologiaO n l i n e