1. DISCUSS THE VALUE OF
PSA & GLEASON SCORE IN
THE MANAGEMENT OF CAP
PRESENTER: AROJU S.A
MODERATOR: DR MAITAMA H
UROLOGY DIVISION,
SURGERY DEPARTMENT,
ABUTH-ZARIA

2. OUTLINE
• INTRODUCTION
• BIOLOGY OF PSA
• PSA TESTING
• GLEASON SYSTEM
• GLEASON GRADE & SCORE
• PSA & GLEASON SCORE IN CaP MGT
• CONCLUSION

3. Introduction
• Prostate is a solid organ located behind the
pubic symphysis from the bladder neck to
the urogenital diaphragm: 3.5 by 2.5cm &
weighs 18 – 26g.
• Composed of 20% glandular & 80%
fibromuscular stroma

4. Introduction…
www.prostatematters.com
• Transition Zone • Anterior Zone
• Peripheral Zone • Central Zone

5. Introduction…
The prostate gland
comprises secretory
epithelium :
epithelial, basal,
neuroendocrine,
connective tissue &
smooth muscles.
Only the epithelial
cells secrets PSA ?

6. Introduction…
• Prostate cancer is the fourth most common
male malignancy worldwide, commonest
malignancy in males > 65 years
• Since the introduction of PSA testing, the
incidence of metastatic disease has
decreased.

7. PSA biology
• PSA is a well established tumour marker
that aids the diagnosis, treatment and
follow up of prostate cancer.
• Discovered in the early 1970s
• First commercial assay was in 1986

8. PSA biology…
• PSA is glycoprotein enzyme secreted into
the seminal fluid by the epithelial cells of
the prostate gland, and periurethral glands.
• Also in women : it’s secreted by the
mammary & periurethral glands.

9. PSA biology…
• Role: is the liquefaction of the seminal
coagulum by cleaving 2 seminal vesicle–
specific proteins, seminogelin I and II, into
LMW soluble protein fragments.
• The exact mechanism by which PSA
accesses the bloodstream remains
unknown.

10. PSA biology…
• There is a strong correlation between the
volume of prostate & PSA
• It is elevated in CAP, BPH, prostatitis,
prostatic infarct & prostatic injury.
• Organ specific – not disease specific

11. PSA biology…
• PSA may be normal in anaplastic cancer,
neuroendocrine tumours, sarcomas,
transitional cell carcinoma, lymphoma and
2º cancer.
• Normal ; i. total : 0 – 4ng / ml
ii. velocity : < 0.75ng / ml /year
iii. Density : < 0.15ng / ml

12. PSA biology…
• PSA velocity: rate of change of serum PSA
An ↑ PSA is considered significant only
when several serum assays are carried out
by the same laboratory over a period of at
least 18months
• PSA density: ratio of PSA to gland volume
PSA level are ↑ apprx. 0.12ng/ml/g of
tissue

13. PSA biology…
Age (yrs) Black men PSA White men
(ng/ml) PSA (ng/ml)
40 – 49 0 – 2.0 0 – 2.5
50 – 59 0 – 4.0 0 – 3.5
60 – 69 0 – 4.5 0 – 4.5
70 – 79 0 – 5.5 0 – 6.5

14. PSA biology…
• PSA exist in blood mainly bound to alpha-
chymotrypsin and only small portion as
free PSA.
• Free /total PSA is useful for distinguishing
CaP from benign causes of ↑ PSA.
• f/t is recommended for mass screening for
CaP

15. PSA biology…
• Studies have found that, in general, men
with CaP have ↓ “free” PSA than men
without prostate cancer.
• Typically, men have a percent-free PSA >
25%. 10% - 25% (intermediate range) and
< 10% (low)

16. PSA testing
• PSA level has been used as a screening
tool for CAP since the mid-1980s.
• Currently, first-line screening for prostate
cancer consists of DRE & serum PSA
levels.

17. PSA testing…
• 30% of men with ↑ PSA will have prostate
cancer confirmed by biopsy.
• 20% of men with clinically significant
prostate cancer have PSA values within the
normal range.

18. PSA testing…
• Combined use of DRE, PSA & TRUS-
guided prostatic biopsy is most effective
for early prostate cancer.
• Nevertheless, the finding of a PSA > 10
ng/ml is suggestive of cancer and > 35
ng/ml is almost diagnostic of advanced
prostate cancer.

19. Why do we need screening for
Prostate Cancer?
1. Rising incidence and mortality rates.
2. Aging population.
3. Current understanding of pathogenesis
limits the use of preventative measures.

20. Why do we need screening for
Prostate Cancer?
4. Therapeutic options for metastatic disease
are palliative.
5. In the pre-PSA era, only 30-40% of
patients presented with localized disease.

21. PSA testing…
ACS recommendations
• Age 50: men at average risk & ≥ 10yr life
expectancy.
• Age 45: men at high risk - African american,
men with 1st degree relative diagnosed at
early age.
• Age 40: men at higher risk – multiple 1st
degree relatives diagnosed at early age.

22. PSA testing…
Informed consent:
• CaP is not always life threatening
i. Most CaP grow slowly
ii. Many men who died of other causes
have autopsy → CaP
iii. 1 in 6 diagnosed of CaP
1 in 34 will die of the dx.

23. PSA testing…
Informed consent:
• Testing helps some men but in others, it
leads to diagnosis & Rx of cancer that
would never cause harm.
• Side effect of CaP Rx – impotence &
incontinence.

24. GLEASON SYSTEM

25. Gleason System
• The Gleason grading was devised in the
1966 by a pathologist, Dr Donald F
Gleason
• And members of the Veterans
Administration Cooperative Urological
Research Group (VACURG).

26. Gleason System…
• The Gleason grading system is based
entirely on the histologic pattern of
carcinoma cells in H&E stained prostatic
tissue sections.
• Grade : 1 - 5
• Score : 2 - 10

27. Gleason System…
• The 1º pattern is the most predominant in
area by simple visual inspection.
• The 2º pattern is the second most common
pattern.
• If only one grade is in the tissue sample,
that grade is multiplied by two to give the
score.

28. Gleason System…
• If the second grade is less than 3% of the
total tumor, the primary grade is doubled to
give the GS.
• Gleason sum / combined Gleason grade /
category score ► synonyms for Gleason
score, but 'histological pattern score' was
the initial 1974 designation.

29. Gleason grades
Grade 1:
The cells are well
differentiated and are
uniformly spaced in a
tight mass.

30. Gleason grades…
Grade 2:
The cancer cells are
differentiated, but are
arranged more
loosely, are more
irregular in shape, and
some cells have
spread to other
prostatic tissue.

31. Gleason grades…
Grade 3:
The cancer is
moderately
differentiated; cells
vary in size and more
cells have invaded
other prostatic tissue.

32. Gleason grades…
Grade 4:
The cancer cells are
irregular, distorted,
poorly differentiated
& considerable spread
(invasion) to other
prostatic tissue.

33. Gleason grades…
Grade 5:
The cancer cells do
not look like normal
cells and have spread
in haphazard
“clumps” of all
different shapes and
sizes .

34. Gleason grades…

35. Gleason grades…

36. Modified Gleason grades
By 1974, data from 1032 patients:
• Pattern 1 & Pattern 2 : same as original
• Pattern 3. Moderately differentiated
glands, may range from small to large,
growing in spaced out infiltrative patterns,
may be papillary or cribriform.

37. Modified Gleason grades…
• Pattern 4. Raggedly infiltrating, fused-
glandular tumour, frequently with pale
cells, may resemble hypernephroma of
kidney.
• Pattern 5. Anaplastic carcinoma with
minimal glandular differentiation, diffusely
infiltrating prostatic stroma.

38. Modified GS
Conference of International Society of
Urological Pathology (ISUP), 2005:
• any aggressive cancer seen on the needle
biopsies should be incorporated to the GS,
even if present in small amount.
• Overall Gleason score
• Worst Gleason score

39. Modified GS…
• OGS – Sum of the predominant & the most
aggressive pattern of all the biopsy cores,
treated as one long core.
• WGS -

40. GS category
• GS ≤ 6 : well-differentiated
low-grade cancer
• GS 7 : moderately differentiated
intermediate-grade cancer
• GS 8 – 10 : poorly differentiated
high-grade cancer

41. Significance of GS
• The Gleason score is used to determine
how quickly a tumor may grow or spread.
• The time for which a patient is likely to
survive following a diagnosis of prostate
cancer is related to the Gleason score.

42. Significance of GS…
• Studies have demonstrated that Gleason
4+3=7 disease is much more aggressive
than Gleason 3+4=7 tumors.
• A study demonstrated that after 5 years of
follow up, men treated for
Gleason 4+3=7 ► 40% risk of progression
Gleason 3+4=7 ►15% risk of progression

43. Pitfalls of the Gleason Score
• The score is subjectively determined by a
pathologist.
• A biopsy may not provide a representative
sample of the entire prostate.

44. PSA & GS in the management
of cancer of the prostate

45. Diagnosis
• Combined use of DRE, PSA & TRUS-
guided prostatic biopsy is most effective
for early prostate cancer diagnosis.
• PSA > 10 ng/ml is suggestive of cancer
and > 35 ng/ml is almost diagnostic of
advanced prostate cancer.

46. Prognosis
The Partin Coefficient Tables
• Important tools in guiding decisions about
effective treatment options for CaP
• They are a way of predicting the cancer's
pathologic stage, which can only be
determined after prostatectomy.

47. Prognosis…
The Partin Coefficient Tables
• Based on PSA, GS & clinical stage, these
tables show the probability of having one
of the ffg pathologic stages of CaP:
i. Organ confined
ii. Capsular involvement
iii. Seminar vesicles involvement
iv. Lymph node involvement

48. Prognosis…
The Partin Coefficient Tables
• Partin Coefficient Table I: PSA = 0.0 - 4.0 ng/ml
• Partin Coefficient Table II: PSA = 4.1 - 10.0 ng/ml
• Partin Coefficient Table III: PSA = 10.1 - 20.0 ng/ml
• Partin Coefficient Table IV: PSA > 20.0 ng/ml

49. AUA, 2000 report
• PSA level can be used to eliminate some
staging investigations:
• A patient with CAP without skeletal
symptoms & PSA < 10ng/ml may not need
radionucleotide studies for bone metastasis
bcs the chances are near to zero.

50. AUA, 2000 report…
• Similarly, CT & MRI are not indicated for
staging in men with clinically localized
prostate cancer and PSA < 25ng/ml.
• Pelvic lymph node dissection in staging
may not be required in patients with PSA
< 10.0ng/ml or PSA < 20ng/ml & the GS
≤ 6.

51. Treatment
Selecting initial treatment requires
assessing the risk of the disease spreading
or progressing, which is based on:
 Life expectancy,
 Comorbidities,
 Biopsy grade (Gleason score),
 Clinical stage, and
 Prostate-specific antigen (PSA)

52. Treatment…
 Patients with clinical stage T1c with :
 Gleason score ≤ 6,
 PSA < 10ng/ml, density < 0.15ng/ml/g,
 fewer than 3 positive prostate cores,
 ≤ 50% cancer in each core, and
 life expectancy < 20y,
Rx : active surveillance

53. Treatment…
Active surveillance
 PSA every 3mo or at least every 6mo;
 DRE every 6mo or at least every 12mo;
 Repeat biopsy within 18mo but as often as
every 12mo or if PSA and DRE change.

54. Treatment…
 Patients with clinical stage T1-T2a with :
 Gleason score 2-6,
 PSA < 10 ng/ml,
 Life expectancy < 10y,
Rx : active surveillance

55. Treatment…
 Patients with clinical stage T1-T2a with :
 Gleason score 2-6,
 PSA < 10 ng/ml,
 Life expectancy ≥ 10y,
Rx : Radical prostatectomy _+ PLND OR
Radiation therapy

56. Treatment…
 Patients with clinical stage T2b-T2c with:
 Gleason score 7,
 PSA 10-20 ng/ml,
 Life expectancy < 10y,
Rx : Active surveillance OR
Radiation therapy _+ ADT

57. Treatment…
 Patients with clinical stage T2b-T2c with:
 Gleason score 7,
 PSA 10-20 ng/ml,
 Life expectancy ≥ 10y,
Rx : Radical prostatectomy + PLND OR
Radiation therapy _+ ADT

58. Treatment…
 Clinical stage T3a,
Gleason score 8-10,
 PSA >20 ng/ml
Rx : Radiation therapy + ADT

59. Follow-up
• Following radical prostatectomy, PSA
should be undetectable after about a
month.
• Cancer recurrence is a PSA > 0.2ng/ml that
has risen on at least two separate occasions
at least two weeks apart and measured by
the same lab.

60. Follow-up…
• PSA velocity & PSA doubling time, both
are very significant in determining the
aggressiveness of CAP.
• Men with ↓ PSA doubling time or ↑ PSA
velocity after initial therapy tend to have
more aggressive disease, and are more
likely to need more aggressive therapies.

61. Conclusion
• Serum PSA has revolutionalized the ability
to detect CAP, though disease nonspecific.
↑ specificity : PSA density, velocity, age
adjusted reference range.
• Gleason score is a good device to
determine aggressiveness & prognosticate
outcome. However, it’s pathologist
subjective

62. References
 Smith general urology, 16th edition. Emil A. Tanagho MD, Jack W.
McAninch MD,FACS
 Bailey & loves short practice of surgery, 25th edition. Norman S.
Williams, Christopher J. K Bulstrode & P. Ronan O’ Connell.
 Principles & practice of surgery including pathology in the
tropics, 4th edition. E.A Badoe M.D, CH.m, FRCS, DTM&H,
FWACS, FGA, DSc, FGCP&S, COV. E.Q Acharpong B.Sc, MS,
FRCS, FICS, FWACS,
 Gleason grading and prognostic factors in carcinoma of the
prostate, Peter A Humphrey. Department of Pathology and
Immunology, Washington University School of Medicine, Saint
Louis, MO, USA. Published online 13 February 2004.
 Percent-Free PSA, Matthew Schmitz, M.D, About.com health's
disease and condition, May 04, 2009.

63. THANK YOU