prostate cancer pre management

1. Prostrate Cancer –
Pre managment
Susheel Yeshala

2. Headings
•Epidemiology
01
•Anatomy
02
•Physiology
03
•Etiology and risk factors
04

3. Headings
•Pathology
•05
•Screening
06
•Diagnosis and workup
07
08 •Staging

4. Headings
•Risk Classification
09
•Diagnosis and workup
10

5. Epidemiology

6. Epidemiology - World
Incidence
70%
• 4th most common cancer in the world
• 2nd most common cancer in men.
• 1.1 million men worldwide were diagnosed in 2012
• 70% of the cases occurring in more developed
regions
• Incidence rates highest in Australia/New Zealand an
d Northern America, Western and Northern Europe.
• low in Asian populations with estimated rates of 10.5
and 4.5 in Eastern and South-Central Asia.

7. Epidemiology - World
Incidence

8. Epidemiology - World
Incidence

9. Epidemiology - World
Mortality
6.6%
• prostate cancer is the 5th leading cause of death
from cancer in men
• 6.6% of the total men deaths
• Mortality larger in less developed than in more
developed regions.
• Mortality rates are generally high in predominantly
black populations

10. Epidemiology - World
Mortality

11. Epidemiology - World
Mortality

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13. Epidemiology - India
• Incidence is on rise in India.
• Increased migration of rural population to the urban are
as, changing life styles, increased awareness, socio-ec
onomic
• Diagnostic and detection technologies have improved a
nd more of the population has not only access, but can
also afford the same.
• (PBCRs) - (2008–2011) - Among top ten leading sites
• Lowest in north east region of India.

14. The PBCRs at Bangalore (APC: 3.4%), Chennai (4.2
%), Delhi (3.3%), Mumbai (0.9%) and Kamrup Urban
District (11.6%) recorded a statistically significant
increasing trend in incidence rates over time.
The actual values of the AARs for the two very
recent PBCRs (Kamrup urban district and Thi'Puram)
for each calendar year.

15. Anatomy

16. Embryology
• The prostate arises from a budding collection of
tissue in the urogenital sinus.
• Develops from epithelial outgrowths form the
prostatic segment of the urethra that grows into
the surrounding mesenchyme
• This outgrowth and branching start at week 10
during embryo growth;
• 12th week - 5 groups of tubules.
1st - Middle lobe.
2nd - Right lateral lobe.
3rd - Left lateral lobe.
4th - Posterior lobe.
5th - Anterior lobe.

17. Prostate
Relations
• 20 g in volume, 3 cm in length, 4 cm wide, an
d 2 cm in depth.
The gland is located
• Posterior to the pubic symphysis,
• Superior to the perineal membrane,
• Inferior to the bladder,
• Anterior to the rectum.
• The base of the prostate is in continuity with t
he bladder and the prostate ends at the apex
before becoming the striated external urethral
sphincter.
• The sphincter is a vertically oriented tubular s
heath that surrounds the membranous urethra
and prostate.

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19. Prostate
Fascia
3 distinct layers of fascia
• Pseudocapsule
• True capsule
• Endopelvic fascia
• Levator fascia
• Denonvilliers fascia

20. Prostate
Anterior Lobe
Portion of the gland lying in front of the urethra.
Completely of fibromuscular tissue.
Median Lobe
Cone-shaped portion of the gland
Between the two ejaculatory ducts and the urethra.
Lateral Lobes
Main mass of the gland and are continuous posteriorly.
They are separated by the prostatic urethra.
Posterior Lobe
Postero-medial part of the lateral lobes
Palpated through the rectum during digital rectal exam
Lobes

21. Prostate
Zones
Divided into 3 zones:
Histologically distinct and anatomically separate
• Central zone
• Peripheral zone
• Transition zone
• 70% glandular tissue
• 30% fibromuscular stroma.

22. Prostate
Zones
Central Zone
• Most of the base of the prostate surrounding the ejaculatory ducts.
• This zone consists of 25% of the glandular tissue.
• Low incidence of Ca Prostate - represent 1-5%.
Peripheral Zone
• This zone covers the posterior and lateral aspects of the prostate.
• Constitutes 70% of the glandular tissue.
• Palpated on digital rectal examination (DRE)
• 70% of adenocarcinomas are found.
• Most commonly affected by chronic prostatitis.

23. Prostate
Histology
Transition Zone
• Surrounds the urethra between the bladder and the verumon
tanum.
• Small Volume - 5% in the normal organ
• Principal site of BPH pathogenesis.
• Nodular expansion of this region of the prostate results in co
mpression of the urethra and the partial bladder outlet obstr
uction associated with BPH.

24. Prostate
Arterial supply
• Internal iliac (hypogastric) artery.
• Inferior vesical artery
• Urethral artery - prostatovesical junction - supply
the transition zone.
• This artery is the main arterial supply for the aden
omas in benign prostatic hyperplasia.
• The capsular artery - second main branch of the -
enters at right angles - supply the glandular tissue
• Seminal vesicals and ductus deferens - artery of
the ductus - superior vesical artery.

25. Prostate
Venous Drainage
• The venous drainage of the prostate starts with the deep
dorsal vein
• The lateral plexuses travel posterolaterally and communi
cate with the pudendal, obturator, and vesical plexus.
• These veins then communicate with the internal iliac vein
.

26. Prostate
Nerve supply and Lymphatics
Innervations
• Sympathetic fibers from the thoracolumbar levels (L1-L2).
• contraction of the smooth muscle of the capsule and the stroma.
• Parasympathetic from the sacral levels(S2-S4)
• The parasympathetic nerves - prostatic secretion.
Lymphatic Drainage
• Obturator and the internal iliac lymphatic channels.
• External iliac, presacral, and the para-aortic lymph nodes.

27. Prostate
Nerve supply

28. Physiology

29. Prostate
Functions
Three Cell Types
• Stromal cells - Provide the structural body of the prostate gland.
• Glandular cells - Production of seminal fluid, Only one tenth to one third of seminal
fluid production
• Smooth-muscle cells, which contract during sexual intercourse, forcing seminal fluid
into the urethra.

30. Prostate
Physiology
Testosterone is transformed to a biologically
active form, DHT (dihydrotestosterone).
• Androgen Receptor
• Bicalutamide

31. Prostate
PSA
• Gamma-seminoprotein or kallikrein-3 (KLK3),
• Glycoprotein enzyme encoded in humans by the KLK3 gene (Chromosome 19)
• Secreted by the epithelial cells of the prostate gland.
• The reference range of less than 4 ng/mL
• Half life of 2-3 days
• It liquefies semen in the seminal coagulum and allows sperm to swim freely.
• Instrumental in dissolving cervical mucus, allowing the entry of sperm into the uterus

32. Prostate
PSA
• Increased levels of PSA (>4ng/ml)may suggest the presence of prostate cancer.
• Digital rectal examination (DRE) has been shown in several studies[1]
• Increased by prostatitis, irritation, benign prostatic hyperplasia (BPH), and recent
ejaculation, producing a false positive result.
1. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley
JJ, Coltman CA (May 2004). "Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter"
. The New England Journal of Medicine. 350 (22): 2239–46. doi:10.1056/NEJMoa031918. PMID 15163773.

33. Etiology

34. Prostate
AGE01
Family
History
02
Genetic
susceptibility03
Race and
Ethnicity
04
Diet and
Lifestyle
05 Others06
Etiology

35. Prostate
Etiology
• Increases with age
• rare before age 40
AGE
• Firstdegree have a 2- to 3-fold
increased risk
• 2/>2 first-degree relatives 5- to
11- fold increased risk
Family History
• HOX13B – Rare, less aggressive
• BRCA2 – Early onset, Lethal
Genetic Susceptibility
• Men of African ancestry
• Diagnosed at a younger age
• Higher frequency of metastatic
disease at presentation
• Lower survival rates
Race and Ethinicity

36. Prostate
Etiology
• high fat intake
Dietary
• Adult obesity
• Physical inactivity
Lifestyle

37. Pathology

38. Prostate
Histopathology
• More than 95% of malignant tumors of the prostate are adenocarcinomas that arise
in acinar and proximal ductal epithelium.
• Grossly - Pale yellow or gray flecks of tissue that is difficult to distinguish from surrou
nding normal tissue
• Adenocarcinomas are often multifocal, heterogeneous, and follow a papillary, cribrifor
m, comedo, or acinar pattern
• A hallmark of prostate cancer is the loss of basal cells, positive staining for alpha-met
hyl-CoA racemase and negative staining for basal cell markers and p63.

39. Prostate
Pathogenesis

40. Prostate
Gleason Grading System
• Assesses the architectural details of malignant gland
s under low to medium magnification.
• Five distinct patterns of growth from well- to poorly dif
ferentiated were originally described by Gleason usin
g a scale from 1 to 5
• Pattern 1 – most differentiated with discrete glandular
formation
• Pattern 5 - most undifferentiated with strands of disor
ganized and loss of the glandular architecture
• Prostate cancers tend to be heterogeneous, with two
or three patterns occurring within a typical prostate.
• So the final Gleason score is the sum of the grades o
f the primary (largest) and secondary patterns, rangin
g from 2 (1 + 1) to 10 (5 + 5).

41. Prostate
Gleason Score

42. Screening

43. Prostate
Screening
The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial
USA
1993–2001
76,685 men
ages 55 to 74
comparing annual PSA for 6 years and DRE for 4 years with opportunistic screening
13-year follow up
Cancer detection rate was slightly higher (RR = 1.12) in the screened arm,
There was no difference in the risk of dying of prostate cancer.

44. Prostate
Screening
The European Randomized Study of Screening for Prostate Cancer (ERSCP)
• European
• Screening with PSA every 2 to 4 years to no screening
• 162,243 men
• Age 55 to 69 years
• median of 11 years
• reduction in prostate cancer mortality was21%
• Number needed to be screened is1,055
• Number needed to diagnose to 37.

45. Prostate
Screening

46. Prostate
Screening

47. Diagnosis and workup

48. Prostate
Signs and Symptoms
• The acute development of pelvic or perineal pain, erectile dysfunction, or hematuria
should prompt further evaluation of the prostate.
• Today, men rarely present with symptoms of metastatic disease such as bone pain,
pathologic fracture, anemia, or pancytopenia

49. Prostate
Work Up
• Prostate cancer is usually suspected on the basis of DRE and/or PSA levels.
• Definitive diagnosis TURP or prostatectomy for benign prostatic enlargement (BPE).
Digital rectal examination
• Most PCas are located in the peripheral zone and may be detected by DRE
• In ~18% of cases, PCa is detected by suspect DRE alone, irrespective of PSA level
• A suspect DRE in patients with a PSA level ≤ 2 ng/mL has a positive predictive value
of 5-30%
• An abnormal DRE is associated with an increased risk of higher GS and is an indicati
on for biopsy

50. Prostate
Work Up
Prostate-specific antigen
• The use of PSA as a serum marker has revolutionised PCa diagnosis.
• Prostate-specific antigen is organ but not cancer-specific,
• May be elevated in benign prostatic hypertrophy (BPH), prostatitis and other non-mal
ignant conditions.
• As an independent variable, PSA is a better predictor of cancer than either DRE or tr
ansrectal ultrasound (TRUS).

51. Prostate
Work Up
PSA density
Prostate-specific antigen density is the level of serum PSA divided by the TRUS-determin
ed prostate volume.
The higher the PSA density, the more likely it is that the PCa is clinically significant.
PSA velocity and doubling time
There are two methods of measuring PSA kinetics:
PSA velocity (PSAV): absolute annual increase in serum PSA (ng/mL/year)
PSA doubling time (PSA-DT): which measures the exponential increase in serum PSA ov
er time
PSAV and PSA-DT may have a prognostic role in treating PCa, but limited diagnostic use
because of background noise (total prostate volume, and BPH)

52. Prostate
Work Up
Prostate biopsy
• Based on PSA level and/or suspicious DRE and/or imaging.
• Age, potential comorbidity, and therapeutic consequences should also be considered
• Risk stratification is a potential tool for reducing unnecessary biopsies
• Ultrasound (US)-guided biopsy is now the standard of care.
• Transrectal or transperineal approach.

53. Prostate
Transrectal ultrasound (TRUS) and ultrasound-based techniques
The normal adult prostate imaged by TRUS ap
pears as a symmetric, triangular, relatively hom
ogeneous structure with an echogenic capsule.
TRUS is used routinely for guidance during the
transrectal biopsy and during prostate brachyth
erapy
Grey-scale TRUS is not reliable at detecting
PCa.
New sonographic modalities such as sonoelast
ography and contrast-enhanced US are still un
der investigation and not ready for routine use.

54. Prostate
CT Scan
The primary role of CT in prostate cancer is for
size determination of the prostate gland,
radiation therapy treatment planning,
assessment of pelvic nodal metastases
Roach et al.175 compared prostate volumes defined by MRI and CT and found a 32
% increase in prostate volume when defined by noncontrast CT scan.
CT lacks the soft-tissue resolution needed to detect intraprostatic disease, capsular
extension, or seminal vesicle involvement.
Routine preoperative CT scanning could not be justified in patients with a PSA of <2
5 ng/mL.
sensitivity of CT for detecting positive nodes is only approximately 30% to 35% even
at these levels.

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Rectal Invasion
T4

56. Prostate
MRI
MRI for PCa detection has largely followed a multiparametric approach.
At least two functional MRI sequences (diffusion-weighted imaging [DWI] and dyna
mic contrast-enhanced imaging) for imaging the different biological characteristics of
the tumor IS required
T2-weighted imaging (T2WI) sequences offer excellent soft tissue contrast and depi
ction of the zonal anatomy of the prostate
Cancer appears as bright hyperintense regions on DW images because restricted
water diffusion in these regions causes less signal loss.
sensitivity, specificity and accuracy are 40%, 95% and 76%, respectively, for focal (i.
e. microscopic) EPE, and 62%, 95% and 88% for extensive EPE

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60. Prostate
Prostate-specific membrane antigen-based PET/CT
68Ga- or 18F-labelled prostate-specific membrane antigen PET/CT (PSMA PET/CT)
Provides excellent contrast-to-noise ratio.
Prostate-specific membrane antigen is also an attractive target because of its specifi
city for prostate tissue,
Sensitivities and 80% (95% CI: 66-89%)
Specificities - 97% (95% CI: 92-99%)
The tracer uptake is also influenced by the GS and the PSA level.
PCa, tumours with a GS of 6, 7(3+4) and 7(4+3) showed significantly lower tracer u
ptake than tumours with a GS of ≥ 8.
Similarly patients with PSA levels ≥ 10 ng/mL showed significantly higher uptake tha
n those with PSA levels < 10 ng/Ml.

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62. Prostate
Bone Scan
99mTc-Bone scan has been the most widely used method for evaluating bone meta
stases of PCa.
A recent meta-analysis
Sensitivity of 59% (95% CI: 55-63%)
Specificity 75% (95% CI: 71-79%)
Bone scan diagnostic yield is significantly influenced by the PSA level, the clinical st
age and the tumour GS
Bone scanning should be performed in symptomatic patients, independent of PSA le
vel, GS or clinical stage

63. Staging –AJCC 8th Ed.

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72. Risk Classification

74. Surveillance

75. Prostate
Surveillance

76. Thank you