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CARCINOMA OF PROSTATE

(MEDICAL STUDENTS LECTURE )

By; NK Dakum MSc ,FMCS, FWACS, FICS,DIP UROL(UK)

Consultant urologist/ Professor, JUTH/Unijos.

Visiting Bingham University Karu

ndakum2001@yahoo.com

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Learning objectives

At the end of this lecture, students will be able to

Appreciate the burden of the disease
Have an idea of the cause
Know the features of the disease
Know the treatment options

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Anatomy of prostate-1

Location- in the lower part of abdomen, behind pubic bone, below urinary bladder
Shape-compressed inverted cone
Zones-peripheral, central,periurethral,(? Preprostatic tissue)
anterior

Prostate Cancer by Dakum NK. 2023

1.Peripheral-70-75% of normal glandular tissue. Site of ca. from urogenital sinus, branches laterally

2.central-glandular, surrounding ejac duct. 25% of glandular tissue. From wolfian duct. In contact with urethra at upper end of verumontanum. 10% ca p.

3.Transition zone-<5% normal glandular tissue. Adjacent to urethra at jxn proximal urethra(preprostatic sphincter) and prostatic urethra. TZ and other periurethral glands are site of BPH. 20% ca p from here.

4. Preprostatic tissue-surround anteriorly displaced urethra. Proximal to upper end of veru. Smaller and most complex part. Has smooth ms. Its sphinteric action at time of ejaculation prevents reflux of semen into bladder.

Figure 32.9 Sagittal diagram of distal prostatic urethral segment (UD), proximal urethral segment (UP), and ejaculatory ducts (E) showing their relationships to a sagittal section of the anteromedial nonglandular tissues [bladder neck (bn), anterior fibromuscular stroma (fm), preprostatic sphincter (s), distal striated sphincter (s)]. These structures are shown in relation to a three-dimensional representation of the glandular prostate [central zone (CZ), peripheral zone (PZ), transitional zone (TZ)]. Oblique coronal plane (OC) of Fig. 32.10 and coronal plane (C) of Fig. 32.11 are indicated by arrows. (From McNeal JE. Normal histology of the prostate. Am J Surg Pathol 1988;12:619, with permission.)

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Anatomy of prostate-2

?Lobes-exist only in embryo-5- 2 lateral, posterior, median,
Function- unknown? Fluid has electrolytes and other substances which contribute to sperm fluid

Prostate Cancer by Dakum NK. 2023

1.Peripheral-70-75% of normal glandular tissue. Site of ca. from urogenital sinus, branches laterally

2.central-glandular, surrounding ejac duct. 25% of glandular tissue. From wolfian duct. In contact with urethra at upper end of verumontanum. 10% ca p.

3.Transition zone-<5% normal glandular tissue. Adjacent to urethra at jxn proximal urethra(preprostatic sphincter) and prostatic urethra. TZ and other periurethral glands are site of BPH. 20% ca p from here.

4. Preprostatic tissue-surround anteriorly displaced urethra. Proximal to upper end of veru. Smaller and most complex part. Has smooth ms. Its sphinteric action at time of ejaculation prevents reflux of semen into bladder.

Figure 32.9 Sagittal diagram of distal prostatic urethral segment (UD), proximal urethral segment (UP), and ejaculatory ducts (E) showing their relationships to a sagittal section of the anteromedial nonglandular tissues [bladder neck (bn), anterior fibromuscular stroma (fm), preprostatic sphincter (s), distal striated sphincter (s)]. These structures are shown in relation to a three-dimensional representation of the glandular prostate [central zone (CZ), peripheral zone (PZ), transitional zone (TZ)]. Oblique coronal plane (OC) of Fig. 32.10 and coronal plane (C) of Fig. 32.11 are indicated by arrows. (From McNeal JE. Normal histology of the prostate. Am J Surg Pathol 1988;12:619, with permission.)

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Epidemiology-1

Commonest malignant tumour in men >65yrs in US, 2^nd worldwide
age adjusted incidence-635 cases /100,000 in men ≥65
incidence in Nigeria- 127/100,000 cases (hospital incidence)
Western world-

40% life time risk of developing prostate cancer,
15% risk of developing symptoms,
3% risk of dying

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INTRODUCTION

Carcinoma of the prostate is the second most common cancer among men with an age adjusted incidence of 635 cases per 100,000 in men aged 65 years and older1. Amongst American men however, it is the most common malignancy accounting for more than 29% of all diagnosed cancers and approximately 13% of all cancer deaths2. It is estimated that one in every six men will be diagnosed with the disease at some time in their lives2 ; making it a major public health problem.

African –American men have been shown to have a 10% higher incidence rate and a 30% higher death rate from all cancers combined than whites3 . For carcinoma of the prostate specifically, African-American men exhibit the highest rates 4,5, although another study suggests Jamaicans have the highest incidence in the world6. Understandably, these are mainly people of African descent. Presentation in this group of people is usually with more aggressive disease than from other ethnic groups4,5. The incidence of prostate cancer in Nigeria, the largest concentration of indigenous black patients in the world is 127/100,000 cases(hospital incidence) with a national prostate

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Epidemiology-2

one in every six men will be diagnosed with the disease at some time in their lives
Latent form found in 30% men >50yrs and 60-80% men >80
Rare before 50yrs but there is steady rise after this age
Increased incidence, death worldwide
Post mortem: 14% males over 50 and 80% those over 70yrs have the disease

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Risk factors -1

Little known
Age->50. strongest risk factor.
Family & genetic factors.

Risk higher if other family members have had or have it.
9% of prostate cancer have hereditary basis.
There is 3-fold increase in men in whom 1^st degree relatives have the disease

Race. More in blacks?
Smoking
Alcohol
Cell behaviour and cell cycle

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Risk factors-2

Probable

Diet: high dietary fat consumption. US > Japan. Red meat increases risk. Intake of fish associated with decreased risk
Hormones( T, DHT). Hardly any cancer in men castrated before puberty

Potential

Vasectomy b4 35 increases risk (not substantiated)
Obesity
Cadmium (eg in cigarette smoke) ↑ risk
High vitamin A intake
Vitamin D deficiency ?
Sexual behaviour?

Those with multiple sex partners,
those who start sex early in life,
Those who have many attacks of sexually transmitted diseases

Prostate Cancer by Dakum NK. 2023

Fat- plenty in US, little in japan.

Hormones-castration. Sexual behaviour-active early, xple partners, h/o std esp hs type II

Alcohol, smoking, obesity.

Total fat intake, animal fat intake, and red meat intake are

associated with an increased risk of prostate cancer, whereas

intake of fish is associated with a decreased risk. There is considerable

controversy on the impact of obesity on prostate

cancer. Some studies suggest that obesity is associated with an

increased risk of more advanced disease and a higher recurrence

rate after treatment. In addition, lycopene, selenium,

omega-3 fatty acids (fish), and vitamin E intake have been

shown to be protective, whereas vitamin D and calcium

increase risk. No dietary supplementation study has yet

shown a tangible benefit in terms of reducing risk of diagnosis

or mortality

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Types of Ca P

Adenocarcinoma-85%
Transitional cell carcinoma (TCC)
Pure primarysquamous cell carcinoma
Sarcomas
Lymphomas
Secondaries

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Spread-local

Urethra
ureter, bladder, seminal vesicle
distal sphincter
rectum,pelvic cellular tissue

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Spread-bloodstream

Bones-vert, femur, ribs,skull, sternum
Spinal cord
Liver, lungs, brain
skin,
palate

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Spread-lymphatic

Int/ext iliacs,
Para-aortic, mediastinal
inguinal
Perineural lymphatics→pain
Involvement may cause lower limb oedema

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Presentation

Asymptomatic
Local disease
Locally advanced disease
Metastatic ds
Widespread mets
Incidental Ca P

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Presentation- Asymptomatic

Routine screening-DRE, PSA
Following TURP or open prostatectomy

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Presentation-Local Ds

LUTS
Irritative- frequency, urgency, nocturia, urge incontinence, pain on micturition, nocturia.?invasion of bladder neck or pelvic nerves
Obstructive- delay, straining, poor stream, overflow incontinence, dribbling, sense of incomplete voiding, intermittency.?urethral compression or BPH effect
Others - haematuria, UTI etc

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Presentation-Locally advanced

LUTS-irritative and obstructive
Haematuria, chronic retention with overflow incontinence
Sphincter

urinary incontinence

Nerves

Suprapubic/perineal pain
impotence

Rectum

Rectal bleeding, constipation
tenesmus,obstruction

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Presentation-metastatic ds

>40% here
Lumbar spine→low back pain, sciatica
Femoral neck → pathological #
Vertebra/ sp cord →paraplegia
Lymph nodes →lymphoedema of LL, anuria, masses

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Presentation-widespread metastases

cerebral →headache,Nausea, Vomiting, drowsiness, epilepsy, paresis
marrow →anaemia, pancytopenia
Uraemia from chr retention & ureteric obs
Lethargy, wt loss, cachexia

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Presentation- incidental CaP

10% following TURP/ enucleation for BPH

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‘Half-time’

‘Fading away like the stars of the morning,

Loosing their light in the glorious sun,

Thus will we pass from the earth and its toiling,

Only remembered by what we have done.’

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DRE findings

Asymmetry of gland
Hard or woody
Nodule, induration
Immobile mucosa
Obliterated median sulcus
Palpable seminal vesicle
Blood on gloved finger
Indistinguishable edges

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Differentials

BPH
Ca bladder
Bladder calculus
Urethral stricture
Bladder neck obstruction
neurogenic bladder
DM, Depression, etc

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Investigations-prostatic bx-1

Confirms diagnosis
Routes

transrectal, transperinal using trucut needle
transurethral using resectoscope

Transrectal ultrasound guided (TRUS) bx preferred

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Investigations-prostatic bx-2

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Ultrasound equipment

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Investigations-PSA

Prostate specific antigen(PSA)
Normal=0-4ng/ml

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Investigations-Extent

URETHROCYSTOSCOPY
URINE M/C/S
UREA, ELECTROLYTES & CREATININE,
(GFR), PCV
ULTRASOUND- KUB (+ PVR)
INTRAVENOUS UROGRAM?
PEAK URINE FLOW RATE( n=≥ 20ml/s),OBSERVE
LFT’s
Lymphangiography
(Histological Gleason grading)

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Ix-radiology

Radiology for mets-

CXR,
Abd X-ray
pelvic/LS X-ray
skull X-ray

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Ix-bone radioisotope scan

Tc⁹⁹ labelled radioisotope
Hot spots

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Ix- CT ,MRI

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Ix- others

Urinalysis
HIV, HbsAg, RBS
ECG

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Treatment of localised ds

Watchful waiting, active surveillance
Radical prostatectomy
Radiotherapy
Others- cryosurgery, Laser, HIFU

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Treatment of advanced disease-Hormonal Tx (Androgen deprivation therapy)

Oestrogens-diethylstilbesterol, phosphorylated DES-(outdated)
Orchidectomy
LHRH analogues-Goserelin(zoladex), buserelin
Anti androgens-flutamide, bicalutamide, nilutamide, etc
Combinations

Prostate Cancer by Dakum NK. 2023

TABLE 33.34. FORMS OF ENDOCRINE THERAPY IN METASTATIC PROSTATIC CANCERa

Ablation of Androgen Sources Orchiectomy

Adrenalectomy

Hypophysectomy

Inhibition of Luteinizing�Hormone–Releasing �Hormone or Pituitary Luteinizing Hormone

Diethylstilbestrol

Chlorotrianisene (TACE)

Conjugated estrogens (Premarin)

Medroxyprogesterone (Provera)

Diethylstilbestrol diphosphate (Stilphostrol)

Polyestradiol (Estradurin)

Cyproterone acetate

Leuprolide

Inhibition of Androgen Synthesis

Medroxyprogesterone

Aminoglutethimide

Spironolactone

Medrogestone

Cyproterone acetate

Antiandrogens

Medroxyprogesterone

Cyproterone acetate

Flutamide

Medrogestone Bicalutamide Nilutamide

�

aSome drugs have multiple sites of action.

Adapted from Elder JS, Catalona WJ. Urol Clin North Am 1984;11:283, with permission.

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Treatment of advanced disease

Localised radiotherapy
Combinations eg radiotherapy +hormonal

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The Treatment Landscape

Local Therapy

Androgen

Deprivation

Therapies After

LHRH Agonists and Antiandrogens

Postchemotherapy

Death

Standard Androgen Deprivation Therapy

Sipuleucel-T

Docetaxel

Cabazitaxel

Abiraterone

Enzalutamide

Radium-223

Denosumab, Zoledronic Acid

Olaparib

Pembrolizumab (MSI-high)

Apalutamide

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Summary

Incidence rising
Aggressive in blacks
Early detection essential-DRE, PSA, education
Trucut bx to confirm diagnosis
Most of our pts present late and undergo orchidectomy. Few rich take drugs

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Merci beaucoup!!

References

Badoe

2 Bailey & Love

3 Gillenwater

4 Campbells

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