Pathology and management of prostate cancer

1. DISCUSS THE PATHOLOGY AND
MANAGEMENT OF PROSTATE CANCER
A PRESENTATION BY
DR. LAWAL G.D.
REGISTRAR, DEPT. OF SURGERY
NHA

2. OUTLINE
• INTRODUCTION
• EPIDERMIOLOGY
• RELEVANT ANATOMY
• PATHOLOGY
• CLINICAL FEATURES
• INVESTIGATIONS
• TREATMENT
• COMPLICATIONS
• PROGNOSIS
• PREVENTION
• CONCLUSION

3. INTRODUCTION
• Prostate cancer is malignant neoplasm of the
epithelium of the prostate
• Approach to prostate cancer diagnosis and
treatment is changing rapidly across the spectrum
of the disease.
• Although the ultimate goal of treatment is to
prolong life, therapeutic objectives in the short
term differ for those in the early versus late states
of the illness.

4. EPIDERMIOLOGY
• Prostate cancer is the commonest male cancer.
• Accounts for 24% of all new male cancer diagnosis.
• However, only 3% of men die as a consequence of prostate
cancer.
• Uncommon before 50yrs
• Post mortem:
- 14% of all males over 50yrs.
- 80% of all males over 70yrs
• The annual incidence in England is about 29,000 cases.
• 140, 143 and 142 cases were diagnosed in 2005, 2006 and
2007 respectively in Ibadan cancer registry.

5. • Up to 43% of men younger than 55yrs of age
have positive family Hx.
• Race - Highest in Negroes (149/100,000
person yr)
- Least in the orients (28/100,000
person yr).

6. RISK FACTORS:
• Not well known
• Hereditary - One 1st line relative – Risk
doubles
- 2 or more 1st line relative
risk x 10
(True hereditary Ca-P (9%) – 3 or more relatives
involved or at least 2 with early Staged disease
with age < 55 yrs)

7. • Age
• Presence of testes – Not seen in men castrated
before puberty.
• Vit D, Vit E, Selenium
• Diet - ↑ saturated fat. Low fibre associated with
higher risk.
• Papilloma virus 33 infection.
• Loss of tumor suppressor genes.

8. RELEVANT ANATOMY

9. PHYSIOLOGY
• PITUITARY – GONADAL AXIS
• Has trophic effect on the prostate

10. PATHOLOGY
• Histologically, 70% of prostate cancer arise from
the peripheral zone.
20% from the transitional zone.
10% from central zone.
1. Adenocarcinoma, constitutes abt 85% of all
cases. Arising from peripheral acinar glands. It is
graded as well, moderately or poorly
differentiated.

11. a. Mucinous Adenocarcinoma, it has more
aggressive biological behavior of progression
and metastases than ordinary adenocarcinoma.
b. Small cell carcinoma, most aggressive with
survival of less than 1year.
c. Neuroendocrine. Rare variant tumor composed
of small or carcinoid-like cell.

12. 2. Transitional cell carcinoma.
3. Squamous cell carcinoma, rare but poor
prognosis.
4. Sarcomas ( e.g leiomyosarcoma) constitutes
about 0.1%.
5. Primary lymphoma
6. Metastatic – as secondaries from other sites.
• N.B: 2-5 Above do not produce PSA

13. STAGING

14. GLEASON GRADING
• It evaluates the architectural details of
individual glands under low to medium
magnification.
• Five patterns of growth from well to poorly
differentiated are described on a scale from 1 to
5.
• Pattern 1 tumors are the most differentiated
whereas 5 are most undifferentiated.

15. • The final Gleason score is the sum of the grades
of the primary and secondary growth patterns.
• Ranges from 2(1+1) to 10(5+5).
• About 85% of tumors are intermediate grade
(Gleason 5 to 7).
• 11% are well differentiated (2 to 4)
• 4% are poorly differentiated cancers (Gleason 8 to
10).

16. Spread – Local, Blood, Lymphatics
• Local – Prostatic urethra, bladder, seminal
Vesicles.
• Blood - Hips, vertebrae
• Lymphatics – perivesical and obturator nodes
→ paraaortic nodes

17. CLINICAL FEATURES
1. Asymptomatic – From routine screening, DRE, PSA
2. Local disease – Lower urinary tract symptoms
-Obstructive
- Irritative
3. Local Invasion:
Urethra – Haematuria, dysuria
Trigone – hydroureters, hydronephrosis
Pelvic nerves – pain, erectile dysfunction
Rectum – Bleeding , constipation

18. 4. Metastatic Disease:
-Vertebrae - Low back pain, Pathological
fractures
-Spinal cord- paraplegia, neurogenic
bladder
-Lymph node enlargement – Lower
limb oedema
-Cerebral metastases
-Skin
-Liver, lungs etc

19. DRE - Gland may be normal
- Hard nodule –hall mark
- Asymmetric enlargement
- Heterogeneous consistency –
hard, soft, firm areas.
- Distorted or absent median sulcus
- Involvement of lateral structures -
winging.
- Palpable seminal vesicles
- Adherence of rectal mucosa

20. DIFFERENTIALS
• BPH
• Ca bladder
• Bladder calculus
• Urethral stricture
• Bladder neck obstruction
• neurogenic bladder etc.

21. INVESTIGATIONS
1. PSA -Organ specific but not disease specific.
-No universally accepted value.
-Recommended values:
a. Total - < 4nglml ; 4 – 10 ng/ml, > 10ng/ml
b. Free / Total (useful in pts with PSA
between 4 – 10)
- N.B: The lower the f/t PSA, the greater the risk
of cancer.

22. c. PSA Density - Takes care of overlap between
Ca-p & BPH.
- Recommended value - > 0.15
highly suggestive of Ca – P.
d. PSA Velocity - Rate of change of PSA with
time.
- At least 3 measurements
within 2 years.
- > 0.75 ng/ml – suggestive of
Ca –P.

23. e. Age Specific PSA :
- sensitivity in younger men
- specificity in older men
40 – 49 - 2.5 ng/ml
50 – 59 - 3.5 ng/ml
60 – 69 - 4.5 ng/ml
70 – 79 - 6.5 ng/ml

24. f. PSA doubling time
-Useful in differentiating local recurrence
from metastatic disease in patients
previously treated for early Ca – P.
- < 6 months – Metastases
- > 6 months – Local recurrence

25. 2. Trans Rectal Ultrasound :- Classic Feature:-
Hypoechogenic area in peripheral zone.
• 3. Prostate Biopsy - Confirms diagnosis
• Routes: transrectal, transperinal (using trucut needle) or transurethral (using
resectoscope)
-Digitally guided needle biopsy
-TRUSS guided (transrectal core needle
biopsy)-gold standard.
-Sextant to 12 cores recommended.
(The greater the no of cores, the greater
the success rate).

26. • URETHROCYSTOSCOPY
• URINE M/C/S, URINALYSIS
• UREA, ELECTROLYTES & CREATININE,
• PCV, LFT
• ULTRASOUND- KUB (+ PVR)
• INTRAVENOUS UROGRAM
• CXR, SKULL AND LUMBOSACRAL
• CT SCAN, MRI
• BONE SCAN

27. TREATMENT
CHOICE OF RX DEPENDS ON:
• Age at diagnosis
• Stage of the dx
• Grade of the tumor
• Co – morbid factors
• Available Rx options
• Pts socioeconomic status
• Pts choice

28. TREATMENT
• Natural History – 75% of men with diagnosis
of Ca-P without treatment will die from the
disease.
A. LOCALISED DISEASE (T1 – T2 NoMo):
i. Watchful waiting/ active surveilance – Ideal
for an asymptomatic man, life expectancy <10 yrs,
low Gleason score.
-Evidence suggest greater risk of death from Ca-
P when compared with treated groups

29. ii. Radical Prostatectomy
- Gold standard
-Retropubic or Transperineal or laparoscopic.
-Not indicated in pts with short life expectancy
-Walsh nerve sparing technique -lower risk of
erectile dysfunction
-Complications: Bleeding, Incontinence, Erectile
dysfunction, Urethral stricture, rectal injury.
iii. Neoadjuvant Hormonal therapy (before sugery
or radiotherapy)

30. iv. RADIOTHERAPY
a. External beam:
-Out come almost as good as surgery
-3 D conformal radiotherapy – Now gold
standard.
b. Brachytherapy
-for very small tumors
-Late complications eg bladder neck stenosis,
erectile dysfunction, bowel problems years
after therapy

31. B. LOCALLY ADVANCED DISEASE (T3):
i. Neoadjuvant hormone therapy + Radiotherapy
-Gold standard
ii. Others:
a. Cryo surgery - Less bleeding
-Similar complications as RP
b. High intensity focused ultrasound (HIFU)
c. LASER

32. C. METASTATIC DISEASE (T4)
i. Hormonal manipulation – Gold standard

33. a. Elimination of testicular testosterone
(Eliminates > 90% of circulating testostene)
ai. Bilateral orchidectomy
aii. LHRH agonist. -Expensive.
-Flare phenomenon
Andropause – main side effect- impotence, loss
of libido, less muscle bulk and bone density, hot
flushes etc

34. aiii. Oestrogens -mechanism- reduce LHRH
secretion, direct reduction in leydig cell function
and direct androgen in-activation.
-e.g Diethyl stilbesterol – Inexpensive but
significant CVS morbidity.
aiv. LHRH Antagonist -No flare phenomenon.
- Rapidly acting. replace LHRH agonists

35. b. Antiandrogens
-Compete with androgen at the receptors
level.
-Inferior to orchidectomy as monotherapy
bi. Non steroidal (Flutamide, bicalutamide)
-Less effect on Libido.
bii. Steroidal (Cyproterone acetate)
-Greater side effect on Libido.
-Expensive.
-Less effective than orchidectomy.
C. Progestogins – Medroxyprogesterone acetate.

36. Maximal Androgen Blockade (MAB) –
-Combination of orchidectomy (or LHRH
agonist or oestrogen) and antiandrogens.
- Blocks both testicular and extra
testicular androgens.

37. Minimal Androgen Blockade ( MIB)
- Finasteride -5 reductase inhibitor –
. PLUS
- Antiandrogen:- Competes with
remaining of DHT for receptors
- Keeps serum testosterone normal,
hence no side effect assoc with
testosterone.

38. Follow-up after curative treatment
Asymptomatic:
- Disease specific history, DRE, PSA – 3, 6
months, then 6 monthly for 3 yrs, then
annually.
- Post RP – PSA - > 0.2ng/ml – Indicative of
recurrence.

39. Post Radiotherapy – Rising PAS, not absolute
value is important.
If recurrence suspected evaluate as
appropriate.
Follow up after hormonal treatment
- Disease specific history
- PSA
- PSA preceeds onset of clinical symptoms by
several months.
- Others e/u/c, Hb, chest x-ray etc.

40. TREATMENT FAILURE
A.For post RP & post radiotherapy patient –
defined as a rising PSA after treatment with
curative intent.
B.Hormone retractory disease –Invariably occurs
in patients managed by androgen deprivation.
-Most patients die within 1 year.

41. Options:
1. Give antiandrogens – if not initially given
2. Withdraw antiandrogens.
3. High dose antiandrogens
4. Oestrogens – Estramustine
5. Ketoconazole
6. Aminogluthetimide
7. Strontium89 - Bone metastases
8. Biphosphonates - bone metastases
9. Hemibody radiation
10. Docetaxel therapy.
11. Steroids
12. Supportive care

42. PROGNOSIS
• Clinical stage at commencement of treatment
• Pretreatment PSA level
• Pathologic tumour differentiation (Gleason
score)
• Age ‹50yrs
• Black race

43. PREVENTION/SCREENING
1. PSA / DRE / TRUSS
2. ↓fat intake
3. Chemo prevention – Finasteride for high
risk groups

44. High Risk Groups
1. High PSA- Negative biopsies
2. Afro-Caribbean ( West African origin)
3. Family history- At least two 1st degree
relatives
- At least one 1st degree
below 55 years.
4. High grade PIN-
Flutamide – Anti androgen
Toremifene- Anti oestrogens.

45. FUTURE TREND
• Public awareness
• Better staging – CT, USS, MRI, PCR
• High intensity focused ultrasound (HIFU) for
T1/T2
• Chemoprevention
• Gene therapy

46. CONCLUSION
• Incidence rising
• Aggressive in blacks
• Trucut bx to confirm diagnosis
• Late presentation and relatively expensive treatment
options present a great challenge to its management
• Early identification of those at risk & institution of
chemoprevention and surveillance strategies will address
some of the current problems of this cancer.

47. REFERENCES
• Principles & practice of surgery including
pathology in the tropics 3rd edition edited by
Badoe.
• 20 common problems in urology edited by Joel
Teichman.
• Adult & paediatric urology 4th edition edited by
Gillenwater.
• Smiths general urology 6th edition edited by Emil
Tanagho.
• Campbells urology 8th edition.
• Essential surgical practice edited by sir Alfred
Cushieri.