this slide is about prostate cancer

1. Prostate Cancer
Zikria, Ph.D.

2. Anatomy
The prostate is a walnut-sized gland located in
front of the rectum and below the bladder.
It surrounds the urethra, the tube-like channel that
carries urine and semen through the penis.
The primary function of the prostate is to produce
seminal fluid, the liquid in semen that protects,
supports, and helps transport sperm.

3. Anatomy
• Blood supply
• – Inferior vesical artery
• • Derived from the internal iliac artery
• • Supplies blood to the base of the bladder and prostate
• • Capsular branches of the inferior vesical artery
• – Help identify the pelvic plexus
• Nerve supply
• – Neurovascular bundle
• • Lies on either side of the prostate on the rectum
• – Derived from the pelvic plexus , arising from the S2-4 (pelvic
splanchnic nerves) and T10-12 nerve roots – thoracic spinal
nerves
• – Important for erectile function.

4. • Peripheral zone (PZ)
• – 70% of cancers
• • Transitional zone (TZ)
• – 20%
• • TZ prostate cancers are
• relatively nonaggressive
• • PZ cancers are more aggressive
• – Tend to invade the peri-prostatic
tissues.

5. Regional Lymph nodes
Pelvic
• Hypogastric
• Obturator
• Iliac (internal, external)
• Sacral
Metastatic Lymph nodes
Distant lymph nodes lie outside the
confines of the true pelvis.
• The distant lymph nodes include the
following:
• Aortic (paraaortic lumbar)
• Common iliac
• Inguinal, deep
• Superficial inguinal (femoral)
• Supraclavicular
• Cervical
• Scalene – neck region
• Retroperitoneal – abdominal cavity

6. Epidemiology
• Family history: 2-3 fold increased risk in men with a
first degree relative.
• • Hereditary association: Early onset of disease and
a Mendelian autosomal dominant inheritance–
accounting for <10% of all cases but 40% in
younger men in <55 years.
• • Racial Factors: Striking differences in incidence
and mortality between the Black and White
population, more common in blacks.
• • Environmental Factors: also responsible for ethnic
differences, as Asians migrating to USA have higher
incidence of prostate cancer.

7. • Diet: one of the most important modifiable risk factors -- high
• fat intake increases risk whereas diets rich in carotenoids
• (tomato based products containing lycopene) and vitamin-E
• are protective.
• • No association with cigarette smoking, alcohol use, height
• and weight and blood group.
• • No data regarding viral origin.
• • No convincing evidence that Vasectomy increases risk of
• prostate cancer

8. Pathology
Adenocarcinoma
95% of prostate cancers
- Developing in the acini of
prostatic ducts
Rare histopathologic types
of prostate carcinoma
- Occur in approximately
5% of patients
– Include
• Small cell carcinoma
• Mucinous carcinoma
• Endometrioid cancer (prostatic
ductal carcinoma)
• Transitional cell cancer
• Squamous cell carcinoma
• Basal cell carcinoma
• Adenoid cystic carcinoma
(basaloid)
• Signet-ring cell carcinoma
• Neuroendocrine cancer

9. Pathophysiology
• In prostate cancer, the cells of
these prostate glands mutate into
cancer cells.
• Mutation is majorly in p53 gene,
BCL2 and ERK5 or alteration in Akt
kinase signaling contribute toward
the development of prostate cancer.
• The prostate glands require
hormones, known as androgens
that are involved in cell survival and
apoptosis.
• Androgens include testosterone,
dehydroepiandrosterone and
dihydrotestosterone.

10. • Initially, small clumps of cancer
cells remain confined to prostate
glands, a condition known as
carcinoma in situ or prostatic
intraepithelial neoplasia (PIN).
• Over time, these cancer cells
begin to multiply and spread to the
surrounding prostate tissue forming
a tumor.
• Eventually, the tumor may grow
large enough to invade nearby
organs such as the nearby lymph
nodes or the rectum, or
metastasize to bone, lymphatic
system and bladder.

11. Risk Factors
Obesity Age Family History
Lower levels of
Vit. D
Prostatitis
Elevated Blood
levels of
Testosterone

12. Clinical Manifestation
• EARLY STAGE
• • Asymptomatic
• • Cancer is in the peripheral
zone
• • LOCALLY ADVANCED
DISEASE
• • Obstructive / irritative
voiding
• Hesitancy
• Intermittent urinary stream
• Decreased force of stream
• --May have growth into the
urethra or bladder neck
• • Retention of urine
•Hematuria
• Hematospermia
• Renal failure
• Pelvic pain
ADVANCED DISEASE (spread to the
regional pelvic lymph nodes)
• Edema of the lower
extremities
• Pelvic and perineal
discomfort
• METASTATIC DISEASE
• Bone pain
• Spinal cord
compression symptoms
• Paraperesis (partial paralysis of both
legs)

13. Hematuria- prostatic urethra/ trigone involvement
• Hematospermia
Extra prostatic spread- often asymptomatic/ extensive dis.
• Rectal involvement-
• Hematochezia (fresh blood through anus)
• Constipation
• Intermittent diarrhoea
• Abdomino-pelvic pain
• Renal impairment due to prolonged bladder outlet obstruction.
• Fluid retention/ electrolyte imbalance

14. Sign and Symptoms
Chronic pain in back, pelvis and hips
Weakness and numbness in legs

15. Diagnosis
• Laboratory
• – Complete blood cell count, blood biochemistry
• – Serum PSA (total, free, percentage free) – prostate specific antigen
• – Plasma acid phosphatases (prostatic/total)
• • Radiographic imaging
• – Transrectal ultrasonography (for biopsy guidance)
• – Biopsy/Needle biopsy of prostate (transrectal, transperineal)
• – Chest radiograph (high risk for metastatic disease)
• – Computed tomography of pelvis.
• – Radioisotope bone scan
• – Magnetic resonance imaging.
• – PET CT Scan for metastasis in high

16. • Abnormal DRE: although correlates poorly with the
volume and extent of cancer, an integral part of the
algorithm.
• • Serum PSA: usually > 4 ng/ml
• With increasing PSA level, chance of getting cancer
increases, but less likely to be organ confined.
• • TRUS guided Biopsy: - Trans-rectal
ultrasonography
• 1) to establish the diagnosis.
• 2) to report extent and grade of cancer in each core.
• 3) to document presence of PNI (perineural
invasion) or ECE (extracapsular extension).

17. PROSTATE
SPECIFIC ANTIGEN
• – Serine protease glycoprotein secreted by prostatic
epithelium
• – Carcinoma specific
• – Normal : 0.4 - 4 ng/ml (upper limit 2.6 ng/ml)
• – t1/2 : 2.2― 3.2 ±0.1 days
• – Mild elevation 4 ― 10 ng/ml
• – Significant elevation >10 ng/ml
• – Sensitivity ― 85%
• – Specificity – 65-70%
• – Estimated rate of cancer detection by PSA screening ― 1.8-
3.3%
• – Carcinoma with normal PSA ― 25%

18. • Age specific PSA :
• – Age PSA
• 40-50 0-2.5
• 60-70 0-4.5
• 70-80 0-6.5
• Pretreatment serum PSA is also predictive of EPE (extra prostatic
extension) and SVI (seminal vesicle invasion):
• PSA Rate of organ-confined disease
• – 4 -10 ng/ml 53% - 70%
• 10 -20 ng/ml 31% - 56%
• Roach’s Probability of ECE, SVI and LNI:
• The risk of positive seminal vesicles (SV+) was calculated using the equation;
SV+ = (PSA) + [10 * {(Gleason score) – 6}].
• The risk of positive lymph nodes (LN+) was calculated using the equation;
LN+ = (0.667 * (PSA)) + (10 * ((Gleason score) - 6))
• The risk of positive capsular penetration (CP+) was calculated using the
equation; CP+ = (1.5 * (PSA)) + (10 * ((Gleason score) - 3))

19. Gleason Scores
• Typical Gleason Scores range from 6-
10. The higher the Gleason Score, the
more likely that the cancer will grow and
spread quickly.
• It is recommended that the primary and
secondary pattern as well as the score be
reported, e.g. Gleason score 3+4=7.
• • If the tumour only has one pattern,
Gleason score is obtained by doubling that
pattern, e.g. Gleason score 3+3=6.

20. • A score of 7 suggests and intermediate risk for aggressive cancer.
• Scoring a 7 means that the primary score (largest section of the
tumor) scored a 3 or 4.
• Tumors with a primary score of 3 and a secondary score of 4 have
a fairly good outlook, whereas cancers with a primary Gleason
Score of 4 and a secondary score of 3, are more likely to grow and
spread.
• Scores of 8 or higher describe cancers that are likely to spread
more rapidly, these cancers are often referred to as poorly
differentiated or high grade.
• Scores of 6 or less describe cancer cells that look similar to normal
cells and suggest that the cancer is likely to grow slowly.

21. Grading
• Gleason X: The Gleason score cannot be determined.
• Gleason 6 or lower: The cells are well differentiated, meaning they
look similar to healthy cells.
• Gleason 7: The cells are moderately differentiated, meaning they
look somewhat similar to healthy cells.
• Gleason 8, 9, or 10: The cells are poorly differentiated or
undifferentiated, meaning they look very different from healthy cells.
• Gleason scores are often grouped into simplified Grade Groups:
• Grade Group 1 = Gleason 6
• Grade Group 2 = Gleason 3 + 4 = 7
• Grade Group 3 = Gleason 4 + 3 = 7
• Gleason Group 4 = Gleason 8
• Gleason Group 5 = Gleason 9 or 10
• Cancer stage grouping

22. Digital Rectal Examination
• Cornerstone of the physical examination/
instrumental in staging
• • Sim’s lateral position.
• – Organ palpation:
• • Craniocaudal and transverse dimension
• • Consistency / Mobility
• • Any firm/ elevated area and its size.

23. •Typical finding a prostate- Hard, nodular, asymmetrical,
may or may not be raised above the surface of gland and
is surrounded by compressible prostatic tissue.
•– Prostatic induration - BHP nodule/ calculi/
infection/granulomatous prostatitis / infarction
•– Specificity- 50% and Sensitivity- 70%
•– Only 25-50% of men with an abnormal DRE have
cancer.
•– DRE + PSA specificity 87%

24. Staging

25. Staging
Stage I: Cancer in this early stage is usually slow growing. The tumor cannot be felt and involves
one-half of 1 side of the prostate or even less than that. PSA levels are low. The cancer cells are
well differentiated, meaning they look like healthy cells.
Stage II: The tumor is found only in the prostate. PSA levels are medium or low. Stage II prostate
cancer is small but may have an increasing risk of growing and spreading.
Stage IIA: The tumor cannot be felt and involves half of 1 side of the prostate or even less than
that. PSA levels are medium, and the cancer cells are well differentiated. This stage also includes
larger tumors confined to the prostate as long as the cancer cells are still well differentiated.
Stage IIB: The tumor is found only inside the prostate, and it may be large enough to be felt during
DRE. The PSA level is medium. The cancer cells are moderately differentiated.
Stage IIC: The tumor is found only inside the prostate, and it may be large enough to be felt during
DRE. The PSA level is medium. The cancer cells may be moderately or poorly differentiated.

26. • Stage III: PSA levels are high, the tumor is growing, or the
cancer is high grade. These all indicate a locally advanced
cancer that is likely to grow and spread.
• Stage IIIA: The cancer has spread beyond the outer layer of
the prostate into nearby tissues. It may also have spread to
the seminal vesicles. The PSA level is high.
• Stage IIIB: The tumor has grown outside of the prostate gland
and may have invaded nearby structures, such as the bladder
or rectum.
• Stage IIIC: The cancer cells across the tumor are poorly
differentiated, meaning they look very different from healthy
cells.
• Stage IV: The cancer has spread beyond the prostate.
• Stage IVA: The cancer has spread to the regional lymph
nodes.
• Stage IVB: The cancer has spread to distant lymph nodes,
other parts of the body, or to the bones.

27. TRANRECTAL ULTRASONOGRAPHY(TRUS)
• Most commonly used to perform an ultrasound-guided needle biopsy
evaluation of the prostate gland in men
• TRUS of the prostate, first described by Wantanabe (1968)
• • TRUS-guided systematic sextant biopsy protocol by Hodge
• • Normal adult prostate : Symmetric, triangular, relatively homogenous
structure with an echogenic capsule
• The paired seminal vesicles are positioned posteriorly at the base of
the prostate.
• They have a smooth, saccular appearance
and should be symmetrical.
• Normal SV measures 4.5
to 5.5 cm(l) and 2 cm (w)
Hypoechoic mass – PSA 100ng/mL

28. • – Sensitivity-66% Specificity- 46%
• Accuracy- 58%
• • Seminal vesicle invasion
• – Echogenic abnormalities
• – Ant. displacement and
enlargement of SV
• TRUS-directed prostate needle
biopsy remains the gold standard
for diagnosis of prostate cancer
• – Guided biopsy of the prostate

29. • • Recommendation: TRUS guided Bx in patients with PSA> 4 ng/ml
• • To establish the diagnosis
• • To report extent and grade of each core
• • To document presence of Pelvic LN involvement and ECE
• – Staging of clinically localized prostate cancer
• – Guidance during the seed/interstitial brachytherapy
• – Monitoring prostate cryotherapy
• – Evaluation and aspiration of prostate abscess
• – Monitoring the response to prostate cancer treatment

30. Imaging
• CXR – chest X-ray
• – Pulmonary metastasis
• – Miliary pattern
• • Axial skeletal survey : Specific sites of bony pain
• – Osteoblastic secondaries
• • USG abdomen-pelvis:
• hydroureteronephrosis - dilatation of the renal pelvis, calyces and ureter
• large post void residual urine volume – ≥ 50mL
• retroperitoneal lymphadenopathy - located in a specific part of the abdominal cavity immediately
behind the intestine that is closer to backbone
• Liver mets.

31. CT Scan
• Primary role
• – Size determination of the gland
• – Assess pelvic LN metastasis
• – Treatment planning in RT
• – Extra Prostatic Extension:
• • Loss of peri-prostatic fat planes
• • Bladder base deformity
• • Obliteration of the normal angle b/w the SV and post. aspect of UB
• – LN involvement
• • Abnormality in size
• • Sensitivity 25%
• • Reserved for patients with higher PSA values (>20-25 ng/ml)
• • CT guided FNAC

32. MRI Scan
• Superior to CT in defining prostate apex, NVB (neurovascular bundle) and anterior rectal wall
• • Better delineation of periprostatic fat involvement
• – T1w- provides high contrast b/w water density structures i.e. Prostate, SV and fat, NVB, perivesical
tissue and LNs
• – T2w fast spine echo- zonal anatomy, architecture of SV
• • Ca Prostate: A focal, peripheral region of decreased signal intensity surrounded by a normal(high
intensity) peripheral zone
• • BHP: centrally located nodules of similar signal
• • Primary staging sensitivity- 69%
• • Endo-rectal surface coil MRI- accuracy of 54-72% staging the primary and detects SVI and ECE –
extra capsular extension

34. • Indications: High likelihood of capsular invasion and LN metastasis
• – Abnormal DRE
• – PSA>20
• – Poorly differentiated ca
• • Sensitivity to locate gland tumor- 79% and specificity- 55%
• • LN detection- Low sensitivity but high specificity

35. MRSI – magnetic resonance spectroscopy
imaging
• Improved diagnostic accuracy of MRI both in localizing and staging and risk
stratifying patients
• – Specificity for tumor location (MRI + MRSI) ~ 91%.
• – Accurate localization of prostate tumors and improved guided biopsy
• – Combined MRI/MRSI enhances the assessment of both ECE and SVI and
capsular breech
• – Predict tumor aggressiveness
• – Distinguishing b/w tumor and post biopsy hemorrhage
• – Detect residual cancer following t/t and follow-up
• – Development of more focused therapy

36. 99Tc BONE SCAN
• • Clinically apparent metastatic disease limited to bone in 80-85% of patients of metastatic ca prostate
• • Osteoblastic secondaries
• • Most common sites of metastasis
• – Vertebral column- 74%
• – Ribs- 70%
• Indications
• Pre-therapy
• – Early stage disease-T1-T2 with
• • PSA > 20 ng / ml
• • GS≥ 8
• • Bony pain
• – T3-T4 –Symptomatic patients
• – High grade tumor

38. Treatment
• 1. Prostatectomy:
Removal of Prostate gland.
• 2. Radiotherapy:
External Beam Radiotherapy:
Radiation directed towards the whole pelvis
externally. Brachytherapy (radioactive seeds): Tiny
radioactive seeds are placed in the body close to
tumor.
• 3. Hormone Therapy:
The goal is to reduce levels of hormones,
called androgens, in the body, or to prevent them
from reaching prostate cancer cells. There are
different types of drugs that lower testosterone
levels.
Luteinising Hormone (LH) Blockers: Luteinising
hormone blockers stop the pituitary gland making
the hormone. So the testicles don't receive the
message telling them to make testosterone.

39. Chemotherapy
• Chemotherapy is sometimes
used if prostate cancer has spread
outside the prostate gland and
hormone therapy isn't working.
• For prostate cancer, chemo
drugs are typically used one at a
time.
• Some of the chemo drugs used
to treat prostate cancer include:
• Docetaxel
• Cabazitaxel

40. • Doxorubicin
• Etoposide
• Vinblastine
• Paclitaxel
• Carboplatin
• In most cases, the first chemo drug given is
docetaxel, combined with the steroid drug
prednisone.
• If this drug does not work (or stops working), a
newer drug called cabazitaxel is given specially in
cases when cancer has stopped responding to
hormone therapy and chemotherapy.

41. Principles of Radiation Therapy (PROS-C)
• External Beam Radiation Therapy
• External beam radiation therapy (RT) is one of the principle treatment options for
clinically localized prostate cancer.
• A dose of 75.6-79 Gy in to the prostate (with or without seminal vesicles) is
appropriate for patients with low-risk cancers.
• Intermediate-risk and high-risk patients should receive doses between 75 and 80
Gy.
• For higher doses (above 75 Gy), daily prostate localization using daily image-
guided radiation therapy (IGRT) is essential for target margin reduction and
treatment accuracy.

42. Brachytherapy
• Brachytherapy involves plaCing radioactive sources into the
prostate tissue.
• Most centers use permanent implants, where the sources are
implanted into the prostate and gradually lose their radioactivity.
• Prostate brachytherapy as monotherapy has become a popular
treatment option for early, clinically organ-confined prostate cancer
(cT1c-T2a, Gleason grade 2-6, PSA < 10 ng/mL).

43. Proton Therapy
• Proton beams can be used as an alternative radiation source.
• Theoretically, protons may reach deeply-located tumors with less
damage to surrounding tissues.
• Palliative Radiation
• Is an effective means of palliating bone metastases from prostate
cancer.
• A short course of 800 cGy x 1 is as effective and less costly than 3000
cGy in 10 fractions.
• Most patients should be managed with a single fraction of 800 cGy for
non-vertebral metastases based on therapeutic guidelines from the
American College of Radiology

57. • Sipuleucel-T (Provenge®) is a cancer vaccine
used to treat advanced prostate cancer. Most
vaccines are designed to prevent diseases, but
this vaccine is aimed at treating prostate
cancer, not preventing it.
• This vaccine is not mass produced. It has to
be made special for each patient from his own
blood cells. To make it, white blood cells are
removed from the patient's blood and sent to
a lab, where they are exposed to a certain
protein from prostate cancer cells. These cells
are given back to the patient into a vein (IV).
Vaccination

58. Prevention
Choose a healthy
diet full of fruits and
vegetables.
1
Choose healthy
foods over
supplements
2
Exercise most days
of the week
3
Maintain a healthy
weight.
4
Talk to your doctor
about increased risk
of prostate cancer.
5

59. Any Question
Special thanks to Prof Dr
Hamid Saeed for graciously
allowing the use of their
insightful PowerPoint slides