3. Introduction
• Prostate cancer is the most common visceral cancer in males in Europe.
• Prostate cancer is the second most common cancer in men worldwide.
• second leading cause of cancer-related deaths in the United States.
• 3rd highest cause of cancer-related death (lung, colon) worldwide.
• Risk factors:
راجل
عجوز
من
إفريقيا
عيلته
فيها
وبيعمل
جميع
متع
الحياة
:
•
بيدخن
•
وباكل
دهون
كتير
•
وبيسكر
•
وبيمارس
الجنس
وقطع
ال
vas
فجاله
إلتهاب
فى
البروستاتا
4. Pathology of Pca
Precurses of prosatic adenocarcinoma:
• atypical small acinar proliferation (ASAP)
• Prostatic intraepithelial neoplasia “PIN”
ADENOCARCINOMA
Other prostatic tumors:
• Small cell carcinoma
• Squamous carcinoma
• TCC
• rhabdomyosarcoma
7. Grading System
Gleason score
• The most commonly used system for grading adenocarcinoma of the prostate
is the Gleason score.
• The system describes a score between 2 and 10, with 2 being the least
aggressive and 10 the most aggressive.
• This score is the sum of the two most common patterns (grades 1-5) of
tumour growth found.
8. Clinical picture:
Asymptomatic:
>80% asymptomatic (elevated PSA or abN DRE) as majority of PCa arises in
periphery
locally advanced:
LUTS, hydronephrosis, ED (N↑B invasion), hematospermia, decreasd ejaculate
volume
Metastatic disease:
bone pain, renal failure, lower limb edema, malignant RPF
Paraneoplastic syndromes as
anemia
hyperCa
hyperPO4
Cushing’s } ectopic ACTH
gynecomastia } increased βhCG
9. For diagnosis:
1. Digital rectal examination (DRE)
2. PSA
3. TRUS Biopsy
For staging:
local staging (T):
• CT scan
• MRI
Nodal staging (N)
• CT scan
• MRI
• laparoscopic pelvic LND
Metastasis (M)
• PXR
• bone scan
• CT scan
• MRI
• Positron-emission tomography.
10. 1 - Digital rectal examination (DRE)
• Most PCa are located in the peripheral zone of the prostate and may be
detected by DRE when the volume is about 0.2 mL or larger.
• The risk of a positive DRE turning out to be cancer is heavily dependent on
the PSA value.
11. 2 - Prostate-specific antigen (PSA)
• PSA is glycoprotein produced by the prostatic secretory epithelial cells which
line the acini and the ducts of the prostate gland.
• Is found in high concentrations in semen and is thought to cause liquefaction
of the seminal coagulum.
• Organ specific but not cancer-specific.
• PSA level is a better predictor of cancer than suspicious findings on DRE or
TRUS.
• Thus, the detection of non-palpable PCa is dependent on the serum level of
PSA.
• There is no universally accepted lower cut-off value, although > 4 ng/mL has
been used in many studies.
12. SOURSES
Prostatic sources
Non-prostatic sources:
• Breast: some types of breast cancers and secreted in breast milk
• Ovaries: some types of ovarian cancers
• Some 1ry lung carcinomas and renal cell carcinoma
• Amniotic fluid
In non prostatic tissues PSA exist in the free form and in clinically non
significant amount
13. • Serum levels may be elevated with BPH, prostatitis and other non-malignant
conditions.
• PSA level is a better predictor of cancer than suspicious findings on DRE or TRUS.
• Thus, the detection of non-palpable PCa is dependent on the serum level of
PSA.
• There is no universally accepted lower cut-off value, although > 4 ng/mL has
been used in many studies.
Risk of PCa in relation to low PSA values
PSA level(ng/mL) Risk of pCa
0-0.5 6.6%
0.6-1 10.1%
1.1-2 17.0%
2.1-3 23.9%
3.1-4 26.9%
14. The following modifications of serum PSA value, may improve the
specificity of PSA in the early detection of PCa:
PSA density
• serum PSA divided by prostatic volume in mL (as estimated by TRUS).
• PSAD > 0.15 determining the need for prostate biopsies.
Age-specific reference ranges
PSA molecular forms
serum PSA complexed antichymotrypsin (PSA-ACT)
Free alpha-2-macroglobulin (PSA-
AMG)
The free/total PSA ratio (f/t PSA) :
• most widely used in clinical practice to differentiate BPH from PCa.
• Cut off value: 25%
PSA velocity
• Rising of the serum PSA level per year.
• (PSAV > 0.75 determining the need for prostate biopsies)
PSA (ng/mL)
Age range (yr)
0-2.5
40-49
0-3.5
50-59
0-4.5
60-69
0-6.5
70-79
15. Other PCa Tumour Markers:
PSMA3 (prostate-specific membrane Ag).
PCA3:
detectable in urine sediments obtained after three strokes of prostatic
massage
Endoglin CD105 “under trial”
It is more accurate than PSA in discrimination of biopsy outcome
17. introduction
when selecting appropriate treatment for PCa you have to put in consideration
1) tumour’s potential aggressiveness
o staging } DRE, imaging, etc
o PSA } total, velocity, doubling time, density, free-to-total ratio, etc
o Gleason score
o N* of cores +ve
o volume of cancer in cores
o perineural or LV invasion
o ductal or neuroendocrine differentiation
2) patient’s general health/co-morbidities
3) patient’s life expectancy
4) QOL preferences of patient
18. Risk stratifi cation of clinically localized prostate cancer
Other
Clinical
stage
Gleason
sum
PSA
(ng/ml)
Risk group
<3 cores positive,
≤50 % tumor in any
core,
PSA density<0.15
T1c
6
<10
Very low
≤T2a
6
<10
Low
T2b
7
≥ 10 and < 20
Intermediate
Lymph node
positive
≥T2c
8
>20
High
20. Active surveillance
• The patient is followed up under close surveillance
until there is evidence of Progression
• intent to cure persists
• Goal is
o distinguish clinically insignificant PCa from life-threatening PCa while still
localized
o avoid overRx while administering curative Rx when indicated
• Recommendations for active surveillance no consensus
o DRE + PSA q3-6months
o repeat Bx 1yr from initial Bx
o Bx q1-2yrs thereafter
27. RADIATION THERAPY
A. external-beam radiotherapy.
B. Brachytherapy
A. External Beam
Technical points : some modification has been done improves local control,
without increasing the morbidity it include
• three-dimensional conformal radiotherapy (3D-CRT)
• intensity-modulated external-beam radiotherapy (IMRT) “gold standard”
B. Brachytherapy
It is implantation of radioactive seeds directly
in prostate to deliver high-dose radiation
28. Cryosurgery of the prostate (CSAP)
Idea uses freezing techniques to induce cell death.
30. Line of management in hormonal therapy
1. First-line hormonal treatment
long-lasting LHRH analogue or antagonist . “medical castration”
Orchidectomy “surgical castration”
2. 2nd line treatment Complete androgen blockade (CAB)
It is blocked adrenal androgens by adding an anti-androgen to either
surgical or pharmacological castration
31. COMPLICATIONS OF ANDROGEN ABLATION
1. Osteoporosis
2. hot flashes
3. sexual dysfunction (ED & loss of libido)
4. cognitive effects
5. Gynecomastia
6. Anemia
7. metabolic syndrome
32. Follow up regimen
• Ther routine follow up is by PSA measurement, disease-specific history
and DRE at the following intervals:
o 3, 6 and 12 months postoperatively,
o every 6 months thereafter until 3 years,
o then annually.
35. Incidence
*Fourth most common cancer in men
*Ninth most common cancer in women
*Represents 7% of all cancers and 3% of all cancer deaths
*Recurrence and routine surveillance/treatment make bladder cancer most
expensive malignancy to treat from diagnosis to death
*M:F = 3:1 (survival better in men)
*Peak incidence ages 60-70
*Majority (~93%) are urothelial cancer (transitional cell carcinoma)
37. Occupations at Risk
• Dry cleaners
• Painters
• Autoworkers
• Truck drivers
• Paper manufacturers
• Metal workers
• Plumbers
• Hairdressers
• Tire and rubber workers
• Chemical workers
• Petroleum workers
38. Pathology
*Transitional cell carcinoma (TCC) 90% of bladder cancers
1973 WHO grading
Urothelial papilloma
Grade 1: well differentiated
Grade 2: moderately differentiated
Grade 3: poorly differentiated
2004 WHO grading system
Papillary lesions:
o Urothelial papilloma (completely
benign lesion)
o Papillary urothelial neoplasm of low
malignant potential (PUNLMP)
o Low-grade (LG) papillary urothelial
carcinoma
o High-grade (HG) papillary urothelial
carcinoma
Flat lesions:
o Urothelial proliferation of uncertain
malignant potential (flat lesion without
atypia or papillary aspects)
o Reactive atypia (flat lesion with atypia)
o Atypia of unknown significance
o Urothelial dysplasia
o Urothelial CIS is always high grade
39. * Squamous cell carcinoma (SCC)
o ~ 5% bladder cancers
o Schistosomiasis esp Egypt (75%)
o Not chemosensitive or radiosensitive
oTreatment surgical – radical cystectomy
* Adenocarcinoma
o~ 2 % bladder cancers
oAssociated chronic UTI
oNot chemosensitive or radiosensitive
oTreatment surgical – radical cystectomy
41. * Carcinosarcoma
Aggressive, not chemosensitive or radiosensitive, 20% five year survival
* Small cell, neuroendocrine
Chemosensitive, Rx neo adjuvant chemo and cystectomy if responds, rare cure
* Leiomyosarcoma
Surgical treatment, cystectomy. 65% five year survival
* Pheochromocytoma
Younger, 20 – 40 years. Adrenergic blockade and care with TURBT
* Leukaemia and lymphoma
* Metastatic tumour
* Rare, more recently breast maetastases. Occasional direct infiltration colorectal
47. Presentation
• Gross hematuria most common
o Most commonly intermittent Gross 68-97%
o Microhematuria 11%
o Timing of hematuria Initial – suggests urethral source
o Terminal – suggests posterior urethra, bladder neck, prostate
o Continuous – suggests bladder etiology
• Irritative voiding symptoms (especially in absence of UTI)
• CP of complication:
o Kidney obstruction
loin pain
impaired renal function
o Chest and bone manifestation
48. Investigation:
Transabdominal US
characterisation of
o renal masses,
o detection of hydronephrosis, and
o visualisation of intraluminal masses in the bladder
Computed tomography urography
Gives more information than US (including status of lymph nodes and
neighbouring organs)
Urinary cytology
The examination of voided urine or bladder-washing specimens for
exfoliated cancer cells has high sensitivity in G3 and high-grade tumours
(84%), but low sensitivity in G1 and low-grade tumours (16%)
Diagnostic cystoscopy and biopsy
50. The diagnosis of papillary bladder cancer ultimately depends on
cystoscopic examination of the bladder and histological evaluation of the
resected tissue.
Perform TURB systematically in individual steps:
bimanual palpation under anaesthesia;
insertion of the resectoscope, under visual control with inspection of the
whole urethra;
inspection of the whole urothelial lining of the bladder;
biopsy from prostatic urethra (if indicated);
cold-cup bladder biopsies (if indicated);
resection of the tumour;
51. Perform resection in one piece for small papillary tumours (< 1 cm),
including part from the underlying bladder wall.
For tumours > 1 cm in diameter perform resection in fractions including:
• the exophytic part of the tumour,
• the underlying bladder wall with the detrusor muscle, and
• the edges of the resection area.
In patients with positive cytology, but negative cystoscopy, exclude:
• a UTUC, CIS in the bladder (random biopsies) and
• Tumour in the prostatic urethra (prostatic urethra biopsy).
52. Perform a second TURB in the following situations:
after incomplete initial TURB;
if there is no muscle in the specimen after initial resection, with the
exception of TaG1 tumours and primary CIS;
in all T1 tumours;
in all HG/G3 tumours, except primary CIS.
53. Disease management
1) Non muscle invasive bladder cancer
(NMIBC)
2) Muscle invasive bladder cancer (MIBC)
54. 1) Non muscle invasive bladder cancer (NMIBC)
Patient stratification into risk groups:
Depending on 6 criteria:
1. Number of tumours
2. Tumour diameter
3. Prior recurrence rate
4. Category Ta or T1
5. Concurrent CIS
6. Grade
55. Plane
Characteristics
Risk group
stratification
One immediate instillation
of intravesical
chemotherapy after TURB.
Primary, solitary, Ta, G1* (PUNLMP, LG), < 3
cm, no CIS
Low-risk
tumours
AS Low risk +
BCG treatment
Between low and high risk
Intermediate-
risk tumours
• Intravesical full-dose
BCG instillations for 1-3
years or
• cystectomy
Any of the following:
• T1 tumour
• G3** (HG) tumour
• CIS
• Multiple and recurrent and large (> 3 cm) Ta,
G1G2 tumours
(all conditions must be presented in this point)
High-risk
tumours
• Radical cystectomy
• intravesical full-dose
BCG instillations for 1-3
years.
T1G3/HG +
• bladder CIS,
• multiple and/or
• large T1G3/HG and/or
• recurrent T1G3/HG,T1G3/HG with CIS in
the prostatic urethra, unusual histology of
urothelial carcinoma, LVI
highest-risk
tumours
56. Effecacy
• Prevent reccurence not progression
• Cross linking agent inhibits DNA synthesis and other mechanisms (alkylating
agent)
• Higher response in CIS (58%) than papillary lesions (43%)
• Role of maintenance therapy uncertain
Side effects:
• Large molecule (334 kd) – minimal systemic absorption and effects
• Chemical cystitis: up to 40% pts
• Decreased bladder capacity
• Skin rash/palmer desquamation (contact dermatitis)
• Leukopenia or bladder contraction is rare
57. Mechanism of action:
Immunomodulatory agent induce inflammatory host response: release
of cytokines
Induction coarse:
• 1st instillation: 1-2 weeks after TURBT
• 6 weekly doses
Dwell time:
1-2 hours
Maintenance coarse:
3 weekly instillations at 3, 6 and 12 months then every 6 months for 3
years
60. Can decrease side effects 30-50% by one of following:
• Decrease dose to 1/3 or less
• Space intervals to 2 weeks instead of 1 week
• Decrease dwell time for BCG to 30 min
• Administer fluoroquinolone 6 and 12 h after each dose
• Use NSAID or COX-2 Inhibitor to potentiate favorable BCG immune response
Contraindication:
Absolute contraindications of BCG intravesical instillation are:
• during the first 2 weeks after TURB;
• in patients with visible haematuria;
• after traumatic catheterisation;
• G3 side effect.
61. Follow-up
The follow-up of Ta, T1 tumours and CIS is based on regular cystoscopy:
Patients with low-risk tumours:
• cystoscopyat 3 months.
• If negative, subsequent cystoscopy is advised 9 months later,
• then yearly for 5 years.
Patients with high-risk tumours:
• cystoscopy and urinary cytology at 3 months.
• If negative, subsequent cystoscopy and cytology should be repeated
every 3 months for a period of 2 years,
• and every 6 months thereafter until 5 years,
• and then yearly.
Patients with intermediate-risk tumours:
should have an in-between follow-up scheme using cystoscopy and cytology.
63. Muscle invasive bladder cancer (MIBC)
• Neoadjuvant chemotherapy
• Pre- and post-operative radiotherapy in MIBC
• Radical surgery and urinary diversion
• Unresectable tumours (T4b)
• Bladder-sparing treatments for localised disease
• Adjuvant chemotherapy
• Metastatic disease
64. Neoadjuvant chemotherapy
T2-T4a, cN0M0 bladder cancer
Cisplatin combination chemotherapy with at least one additional
chemotherapeutic agent eg Methotrexate, vinblastine, adriamycin plus
cisplatin (MVA(E)C)
• Tolerability of chemotherapy and patient compliance are expected to be
better pre-cystectomy.
• Patients might respond to NAC and reveal a favorable pathological status,
determined mainly by achieving pT0, pN0 and negative surgical margins.
65. Pre- and post-operative radiotherapy in MIBC
it can result in tumour downstaging after 4-6 weeks.
• In locally advanced BC (T3- T4, N0/N1, M0),
• the local recurrence rate seems to decrease with post-operative RT.
66. Radical surgery and urinary diversion
Indications
• Patients with MIBC T2-T4a, N0-Nx, M0.
• Other indications include:
o High-risk and recurrent superficial tumours,
o BCG-resistant Tis,
o T1G3as well as
o Extensive papillary disease that cannot be controlled with TURB and
intravesical therapy alone.
• Salvage cystectomy is indicated in:
o Non-responders to conservative therapy,
o Recurrence after bladder sparing treatment,
• Non-urothelial carcinoma
67. Technique and extent
• In men:
Standard RC :
Includes removal of the bladder, prostate, seminal vesicles, distal ureters,
and regional lymph nodes.
• In women:
standard RC:
Includes removal of the bladder, entire urethra and adjacent vagina,
uterus, distal ureters, and regional lymph nodes.
• Standard lymphadenectomy :
o cranially up to the common iliac bifurcation,
o with the ureter being the medial border, and
o including the internal iliac, presacral, obturator fossa and external iliac
nodes
68. Three alternatives are currently used after cystectomy:
• Abdominal diversion: Such as
o Ureterocutaneostomy,
o Ileal or colonic conduit, and
o Various forms of a continent pouch;
• Urethral diversion:
orthotopic urinary diversion
• Rectosigmoid diversions:
Such as uretero- (ileo-)rectostomy.
69. Conduits (small bowel or large bowel)
• Advantages:
o Simple and quick procedure (less OR time)
o Few inherent complications
o Time tested – longest F/U data
o Can compensate for short ureters
• Disadvantages:
o Visible stoma
o Negative body image
o Need for lifelong stoma care (external appliance)
o Anxiety of urinary leakage/odor
70. Continent Urinary Diversion
Patient Selection:
• Serum creatinine < 2
• Adequate Liver function
• Adequate bowel function
• Able and willing to perform self-catheterization
• Patient compliance (agrees to lifelong f/u)
• Absence of short gut syndrome/IBD Colonoscopy prior to using any colon
for diversion
77. ** Palliative cystectomy
** Supportive care
Obstruction of the UUT
• PCN
• Ureteral stenting
• Urinary diversion
Bleeding and pain
• Treatment of general causes
• Transurethral (laser) coagulation
• Radiation therapy
• Non-conservative options (Embolisation)
78. • Indication:
o PT3/4 and/or
o Lymph node positive (N+) disease
o ? Without clinically detectable metastases (M0).
o (If no neoadjuvant chemotherapy has been given).
• Regimen:
Three or four cycles of (cisplatin-based combination):
79. Chemotherapy:
Treatment of bone metastases
• Bisphosphonates:
• Zoledronic acid (ZA)
• Aggressive calcium and vitamin D supplementation
Targeted Therapy
80. 1) Initiation
• Mutation of Protooncogen
• Tumor suppressor gene
• Gene controling DNA repair
• Gene regulating apoptosis
2) Promotion
• Growth factors
• Angiogenesis
• Tolemerase
3) Progression
• Loosening of tumor cells
• Att of tumor cells to basement membrane
• Local degeneration of BM
83. • The most common type of kidney cancer is Renal Cell Cancer,
• also called Renal Adenocarcinoma or Hypernephroma.
• RCC represents 2% of overall cancer incidence and mortality
• 50,000 cases diagnosed and 13,000 deaths annually in the US
84. Epidemiology
Male predominance (1.6:1.0 M:F)
Highest incidence between age 60-80
• Median age of diagnosis is 66 years
• Median age of death 70 years
Highest incidence in Scandinavia and North America, lowest in Africa
No racial differences in the US
85. Risk Factors
Majority of RCC occurs sporadically
Tobacco smoking contributes to 24-30% of RCC cases
- Tobacco results in a 2-fold increased risk
Occupational exposure to cadmium, asbestos, petroleum
Obesity, HTN
Chronic phenacetin or aspirin use
Acquired polycystic kidney disease due to dialysis results in 30%
increase risk
86. Genetic Factors
VHL gene mutation associated with 60% sporadic RCC
2-4% of RCC associated with inherited disorder
Von Hippel-Lindau disease
AD familial cancer syndrome of
• retinal angiomas,
• CNS hemangioblastomas,
• pheochromocytomas and
• clear cell RCC.
87. Clinical Presentation
Variety of symptoms, most asymptomatic
Hematuria present 40% of patients
Classic triad: flank pain, hematuria, palpable abdominal mass occur
in 9% of patients
45% present with localized disease, 25% with locally advanced
disease, 30% with metastatic disease
Paraneoplastic syndromes
88. Paraneoplastic syndromes
Anemia- anemia of chronic disease 29-88%
Hepatic dysfunction in the absence of mets 21%
Hypercalcemia 15%
Cachexia and Fever 20%
Erythrocytosis: 1-5% produce erythropoietin
Secondary AA amyloidosis 3-5%
89. Diagnosis
No screening for the general population
Radiographic evaluation
Ultrasound: solid vs. cystic lesions
Contrast CT: test of choice to evaluate tumor size, location,
lymph node involvement
MRI: to evaluate collecting system and IVC involvement
90. Tissue Diagnosis
Tissue diagnosis obtained from
nephrectomy or biopsy of
metastatic lesion
Surgery indicated for solid renal
masses >1.5cm
Tumors <1.5cm require periodic
follow-up
95. Plane
1-localized disease: T1,T2,T3a
1. Radical nephrectomy
2. Laparoscopy
3.Nephron sparing surgery
4. Minimal invasive therapy
• Cryosurgery
• RFA
• Micro wane thermotherapy
• High intensity focused US
• Interstitial laser therapy
• High energy shock wave
96. 2- RCC with venous extension: T3B,T3C
• Radical nephrectomy
• Tumor thrombectomy
• Adjuvant immunotherapy
3- Locally invasive RCC T4
• Surgery
o Extended Radical nephrectomy. i.e: radical + excision of involved
(bowel,spleen, abdominal wall)
o Partial excision of large primary tumor (debulking)
5 year survival 5 %
• Pre & post operative radiotherapy replaced by immune
• Immunotherapy
• Trans arterial immbolization
(radioactive seed & chemotherapeutic agent)
97. 4- Metastatic RCC M1
Surgical:
• If tumor deposites are resectable( Radical nephrectomy, excision
of deposites)
• If not resectable
o Palliative nephrectomy if ( sever pain, hematuria,
paraneoplastic syndrome, compression of surrounding)
o Or trans arterial immbolization
Systemic
-immunotherapy
- chemotherapy
- radiotherapy
-hormonal therapy
98. Immunotherapy
Immunotherapy with IL-2 activates immune response against RCC
resulting in tumor remission rates 10-20% with median duration of
19-91 months
Severe toxicity including hypotension, MI, renal insufficiency,
pulmonary edema, hepatic dysfunction, CNS dysfunction
Treatment requires ICU monitoring
Used for patients that can tolerate side effects
99. Chemotherapy
RCC is only minimally responsive to chemotherapy
83 clinic trials involving over 4000 pts, overall response rate is only
6%
On-going clinical trials of combination chemotherapy including
Gemcitabine and 5-FU
Limited data reveals some response in non-clear cell RCC to
Carboplatin, Cisplatin plus Gemcitabine
100. Radiation Therapy
RCC relatively radioresistant
XRT has limited use in metastatic disease
-Painful bone or recurrent abdominal metastases
-Brain metastases