Prostate carcinoma- diagnosis and staging

DIAGNOSIS and STAGING OF
PROSTATE CANCER
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai
1

Moderators:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2

Demographics
• Age
○ ↑ risk with age; rare < 50 years
○ Median age at diagnosis: 68 years old
• Ethnicity○ African Americans > Caucasians
• Epidemiology
○ Lifetime risk: 1 in 6 men (developedcountries)
○ 2nd most common cause of cancer death in men after lung cancer
○ in india, 3rd leading cancer in men (7%)
3
Dept of Urology, GRH and KMC, Chennai.

Natural History
• Prostate cancer rarely causes symptoms at an early stage.
• The presence of symptoms suggests locallyadvancedor metastatic
disease.
• Locally advanced CPr: obstructive/irritativeurinary symptoms, ureteral
obstruction causing renal failure, hematospermia or decreased ejaculate
volume, impotence.
• Metastatic disease: bone pain, pathologic fractures, anemia, and lower
extremity edema
• Less common: malignant retroperitonealfibrosis, paraneoplastic
syndromes, disseminated intravascular coagulation (DIC), and paralysis.
4

How is Prostate Cancer Diagnosed?
a. DRE
b. PSA test
c. Transrectal ultrasound (TRUS)
d. Diagnosis is confirmed with a biopsy
e. Imaging tests can determine if the cancer has spread
5

Digital Rectal Exam (DRE)
About 75% of all prostate cancers arise in the outer part of
the prostate where they may be detected by a digital rectal
exam (DRE), which is the simplest and most widely-performed
screening procedure.
Only 20% of men with abnormal DREs have cancer.
About 60% of men who have prostate cancer have normal
DRE results.
6

Digital Rectal Exam (DRE)
“Hard and nodular prostate”
Barnes et al, (degree of prostateencroachment into the
rectum)
RECTAL PALPATION
• Normal : Encroaches 0-1 cm into rectal lumen
• Gr 1 : Encroaches 1-2 cm into rectal lumen
• Gr 2: Encroaches 2-3 cm into rectal lumen
• Gr 3 : Encroaches 3-4cm into rectal lumen
• Gr 4: Encroaches more than 4 cm into rectal lumen
(one finger width is roughly equivalent to 1.5 cm)
7

• Most PCas are located in the peripheral zone and may be
detected by DRE when the volume is > 0.2 mL.
• 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 (PPV) of 5-30%
• An abnormal DRE is associated with an increased risk of a
higher ISUP grade and is an indication for biopsy
8

PSA
9

PSA
10

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12

Prostate Biopsy
Indications:
• Abnormal DRE regardless of PSA
• Abnormal PSA velocity (.75 ng/dL/yr)
• PSA > 4.0 or age appropriate range
– Consider decreasing in men in 40’s, 50’s or with risk factors
(FH/American)
13

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IMAGING
Transrectal ultrasonography (TRUS)
• Hypoechoic lesion in PZ
• Primary use
– Assessment of prostate size and PSAD.
– Guide for biopsy
– Brachytherapy seed placement
○ Limitations
– Limited accuracy (62%)
- False-negative: > 40% of cancers are isoechoic; 15% are
hyperechoic
- False-positive: Prostatitis may appear hypoechoic
○ Color Doppler and power Doppler ↑ accuracy
18

Imaging
TRUS
provides more accurate local staging than
does DRE
Sonographic criteria for Extracapsular extension(ECE):
 bulging of the prostate contour or
 angulated appearance of the lateral margin
19

Imaging
TRUS
sonographic criteria for seminal vesicle invasion:
posterior bulge at the base of the seminal vesicle or
asymmetry in echogenicity of the seminal vesicle
associated with hypoechoic areas at the base of the
prostate
20

Imaging
TRUS
Axial transrectal ultrasonographic (TRUS) scan shows extensive hypoechoic area
(arrows) in the right peripheral zone. 21

PDI
• Power Doppler imaging utilizes amplitude shift to
detect flow in a velocity and directionally independent
manner .
• Advantages :
- detects slower flow and flow in small vessels;
- have less reliance on the Doppler angle
- suitable for detection of prostate cancer neovascularity.
22

23

• Transrectal ultrasound is no more accurate at
predicting organ-confined disease than DRE.
• Transrectal US-derived techniques (e.g. 3D-TRUS,
colour Doppler) cannot differentiate between T2 and
T3 tumours with sufficient accuracy to be
recommended for staging.
24

CT Scan
• Limited role in detecting and staging CPr
○ Poor soft tissue resolution makes it impossible to define zonal
anatomy
• Primary use:
Evaluation of advanced disease,
○ Lymphadenopathy
○ Bone metastases (osteoblastic)
Usually, LNs with a short axis > 8 mm in the pelvis and > 10 mm
outside the pelvis are considered malignant.(Decreasing these thresholds
improves sensitivity but decreases specificity)
25

MRI
ROLE:
- to perform targeted Prostate biopsies
- to stage the pts for locoregional extent of disease
- To plan prostatectomy and NVB preservation
• T1WI
○ Normal appearance of prostate gland – Low SI with poor
differentiation of PZ and TZ
○ CPr appearance: Isointense to surrounding prostate
○ Advantage: High SI of post-biopsy hemorrhage
(methemoglobin)
26

• T2WI
○ Normal appearance:
– PZ : 70% volume of gland; High and homogeneous SI
– TZ : 5% volume of gland; surrounding proximal prostatic urethra;
(Enlargedin BPH- heterogeneous SI: "Organized chaos“)
– CZ : 25% volume of gland; Low SI cone-shaped structure surrounding
ejaculatory ducts.
○ CPr appearance:
– PZ : Low SI lesion confined to prostate or with extracapsular extension
(ECE: Breech of capsule, obliteration of rectoprostatic angle, invasion
into NVB and seminal vesicles)
– TZ : □ Ill-defined, lenticular shape, homogeneous low SI lesion (erased
charcoal drawing sign)
□ Invasion of anterior fibromuscular stroma 27

○ Advantages:
– High sensitivity for tumor detection
– Assessment of ECE
□ Bulging prostatic capsule □ Disruption of prostatic capsule
□ Obliterationof rectoprostatic angle □ Asymmetry/encasementof
neurovascular bundle
□ Asymmetric low SI in seminal vesicles
○ Limitations
– False-positives: Biopsy-related hemorrhage,prostatitis, fibrosis,
radiotherapy
– Tumors in TZ are difficult to differentiatefrom surrounding gland
28

• T1WI C+ / DCE
○ CPr appearance :
– Qualitative (visual) analysis: Early hyperenhancement; rapid washout
– Semiquantitative analysis: Type III curve (increase followed by decline)
most suspicious for cancer
– Quantitative analysis: ↑ Ktrans (forward volume transfer constant);
↑ Kep (reverse reflux rate constant)
○ Advantages:
– Improved diagnosticaccuracy when combined with T2WI and DWI
– Improved assessmentof ECE when combined with T2WI
– Detection of tumor recurrence
○ Limitations:
– False-positive:Prostatitisin PZ, and BPH in TZ
– Lack of standardization for acquisitionand analysis
29

• DWI
○ Normal prostate gland:
– PZ: Homogeneous high SI on ADC map
○ CPr appearance:
- Focal area of high SI on DWI (b value > 800/1,000 s/mm²) and low SI on
ADC map
○ Advantages
– Informationon tumor aggressiveness (ADC values correlatewith Gleason score)
– Specificityof T2WI + DWI > T2WI
○ Limitations
– Poor spatial resolution; susceptible to motion and magnetic field
inhomogeneities
– ADC values depend on field strengthand b value
30

• Low ADC( apparent diffusion coefficient)is associated with higher
Glreason score (inversely related).
• This relationship is strongest in PZ.
• ADC <850 (10 -6 mm2/S) is a reliable predictor of gleason sum >/= 7.
• Score 850 – 1150 is indeterminate;>1150 indicates Benign or low gleason
score histology.
• ADC is fairly repeatable.
31

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33

• MRS (spectroscopy)
○ Dominant compounds in prostate gland – Citrate (2.60 ppm) , Creatine (3.04
ppm) , Choline (3.20 ppm)
○ PC appearance:
– ↓ citrate level; ↑ choline level
– ↑ choline + creatine : citrate ratio
○ Advantages:
– Increased specificity
– Informationon tumor aggressiveness
○ Limitations:
– Increased total acquisition time
– High expertise required, prone to artefact, time intensive
34

• Elevated choline:citrate ratio and elevated choline + creatine :
citrate ratio (0.22 +/- 0.0013) are spectroscopic indicators of
prostate cancer.
• Choline is a marker of cellular proliferation because it is
incorporated into cell walls.
• Citrate is a marker of normal prostate tissue and BPH.
• The spectroscopic peak of creatine is often inseparable
from the spectroscopic peak of choline,
• so they are often summed together (choline + creatine :
citrate ratio).
35

36

Imaging Recommendations
• Best imaging tool
○ mpMR
– Detection (PZ cancer): Sensitivity 81%, specificity 91%
– Staging: NPV for ECE 95%
– Active surveillance
– Guidance for biopsy
– Post-treatment follow-up
• Protocol advice
○ Multiplanar mpMR
– High-resolution T2WI + □ DWI □ Dynamic contrast-enhancedMR (DCE-MR)
□ MR spectroscopy (MRS [optional])
– Pelvic phased array coil + endorectal coil
– 1.5T-3.0T magnet
– > 6 weeks post biopsy 37

PIRADS Score
(Prostate Imaging Reporting and Data System)
• 1 = Highly unlikely for the presence of clinically significant
prostate cancer
• 2 = Unlikely for the presence of clinically significant prostate
cancer
• 3 = Equivocal/uncertain
• 4 = Likely for the presence of clinically significant prostate
cancer
• 5 = Highly likely for the presence of clinically significant
prostate cancer
38

• Given its low sensitivity for focal (microscopic) EPE,
mpMRI is not recommended for local staging in low-
risk patients. However, mpMRI can still be useful for
treatment planning.
• High-resolution MRI used in tandem with the i.v.
administration of lymphotropic superparamagnetic
nanoparticles may allow the detection of small and
otherwise undetectable lymph node metastases .
39

Bone Scan/scintigraphy
• Single-photon scintigraphic imaging is performed using a bone-seeking
radiotracer 99mTc-methylene disphosphonate (99mTc-MDP).
• This radiotracer mimics high metabolic states of fast-growing cancer cells
align the nuclear camera to quantify these areas using a bone scan index.
• ↑ uptake in bone metastases, Osteoblastic.
• Location: Pelvis, thoracic and lumbar spine, ribs
• has relatively poor specificity (42%) for osteoblastic bone metastasis.
• False positive - Paget’s disease, prior trauma, infections, or metabolic
disorders such as hyperparathyroidism.
40

Consider Bone Scan if :
PSA > 20 ng/ml
Gleason grade > 7
Disease is locally Advanced (T3-T4)
CLINICAL SYMPTOMS
Post-treatment follow-up (biochemical recurrence post RP, or
increasing PSA or abnormal DRE after radiotherapy)
41

42

• PET
- used for cancer staging, assessing biochemicalfailure after radiotherapy,
or metastatic involvement
- used in conjunction with anatomical imaging in the form of PET/ MRI or
PET/CT
- different PET methods are characterizedby the choice of tracer used and
the targeted biological process:
- Metabolism : 18 F-fluodeoxyglucose/FDG (most common radiotracter
used to monitor glucose metabolism in tumor cell)
- cellular proliferation: 1-amino-3-fl uurine-18fluorcylobutane-1-carboxylic
acid/18-FACBC, 11C-choline, and 18 F-flurocholine.
- receptor binding: PMSA-basedradiotracers => 64 Cu-labeled aptomers
and 11C-, 18F-, 68Ga-, and 86Y-labeled low molecular weight inhibitors of
PSMA
43

○ 18F-FDG
– Limited for detection and staging of tumor (poor tumor uptake;
interferencefrom excretion into bladder)
○ 11C-choline; 18F-fluorocholine
– Role in restaging patients with biochemical failure (PSA relapse) after
treatment
• 18F-sodium fluoride (18F-NaF) PET or PET/CT shows similar specificity and
superior sensitivity to bone scan.
• unlike choline PET/CT, 18F-NaF PET does not detect LN metastases
• 68Ga-PSMA PET/CT - increased detection rates with respect to
conventional imaging modalities (bone scan and CT) .
• 68Ga- or 18F-labelled prostate-specific membrane antigen PET/CT (PSMA
PET/CT) provides excellent contrast-to-noise ratio, thereby improving the
detectability of lesions.
44

45

Pelvic lymphadenectomy
INDICATIONS:
• Gleason score greater than 8,
• extraprostatic extension on DRE,
• PSA value greater than 20 ng/mL,
• suspicion of enlarged lymph nodes on radiologic
evaluation
(is rarely performedin the contemporaryPSA era.)
46

ProstaScint scan
• It is a murine monoclonal antibody radioimmunoscintigraphy
(radiolabeled monoclonal antibody scan: In-111 capromab
pendetide)
• used for identification of microscopic cancer deposits in
regional and distant sites.
• Detection of recurrent disease
• Can be used as adjunct to CT and Bone scan in detection on
metastatic CrP
• Suboptimal PPV and Specificity
• It has got limited accuracy in the detection of lymph node
metastases because the antibody targets an intracellular
epitope that is exposed only in dying or dead cells. 47

Molecular staging
detection of circulating levels prostate cells
(CTC) in the peripheral blood of men with CaP
(CellSearch)
RT-PCR
uses peripheral blood samples & attempts to
identify the presence of the mRNA to PSA
(indirect evidence of prostate cells in the peripheral circulation)
48

Gene Expression – Tumor Marker
• Advances in proteomic technologies(SELDI-TOF, surface enhanced
laser desorption/ionization – Time of flight) mass spectroscopy offer the
potential to identify the presence of disease from human
serum and other body fluids and may also provide new targets
for diagnosis and therapy.
 α-Methylacyl Coenzyme A Racemase has been found to be upregulated
in prostate cancer tissues.
 Hepsin is a type II transmembrane serine protease
Immunohistochemical studies have shown abundant (90% cases)
staining of hepsin in tumor cell membranes.
 Expression of the DD3PCA3 protein has been localized to prostatic tissue
and has been found in 95% of prostate cancer and prostate metastasis
specimens
49

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52

• Clinical T stage only refers to DRE findings; imaging findings
are not considered in the TNM classification.
• Pathological staging (pTNM) largely parallels the clinical TNM,
except for clinical stage T1c and the T2 substages.
• All histopathologically confirmed organ-confined PCas after RP
are pathological stage T2
• current Union for International Cancer Control (UICC) no
longer recognises pT2 substages
• T3b disease does not distinguish between bilateral and
unilateral SVI (bilateralSVI was associatedwith markedly worse 5-year
biochemicalrecurrence-freesurvival.)
53

- SVI decreases long-term
survival in radical
prostatectomy patients.
- An early study on the
natural history of pT3b
disease without nodal
involvementor metastases
(T3bN0M0) demonstrated
that SVI decreased 7-year
survival rate from 67% to
32%.
Type1: MC, poor prognosis
Type3: least common
(IES – invaginated extraprostatic
space)
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Prostate carcinoma- diagnosis and staging

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