NEOPLASMS OF

GENITOURINARY TRACT
Introduction
 Common sites:
 Prostate
 Bladder
 Kidney
 Others:
 Testes: rare, in younger adults
 Ureter, urethra and penis- rarer
RENAL CARCINOMA
 Also Known as
 Hypernephroma
 Grawitz’s tumor
 third most common genitourinary
neoplasm
 most common: adenocarcinoma
(90%)
 males, 7th decade
Etiology of Renal Cell Carcinoma
 estrogens
 diet- fats, obesity
 renal failure
 hemodialysis
 von hippel lindau disease
 cigarette smokers
 metals- lead and cadmium
Histologic types of RCC
 CONVENTIONAL (70 t0 80%)
 (A)Clear cell carcinoma
 round/polygonal cell, abundant cytoplasm with glycogen
 (B)Granular cell carcinoma (12%) :
 Granular cytoplasm with abundant mitochondria
 (C)Sarcomatoid(1-5%) :
 spindle/pleomorphic cell, worst prognosis
 PAPILLARY ( 10-15%)
 CHROMOPHOBE (4-5%)
 COLLECTING DUCTS (<1%)
 MEDULLARY CELL (<1%)
 ONCOCYTOMA (3-7%):
 large number of mitochondria, rare
CLINICAL PRESENTATION
 ASYMPTOMATIC  Paraneoplastic
 Classical clinical triad syndromes(20%)
(<10%) Elevated ESR
 Hematuria (60%) Hypertension
 Abdominal pain (40%) Anemia
 Palpable mass (45%) Cachexia, Weight Loss
 Secondaries: Pyrexia
 bones and lungs Abnormal LFT ( Stauffer’s
 liver Synd)
 adrenals, brain Hypercalcemia
Polycythemia
Neuromyopathy
Amyloidosis
TNM Staging
 T1: <7cm
 T2: >7cm
 T3:
 T3a- adrenal/ perinephric
 T3b- RV/IVC
 T3c- IVC above diaphragm
 T4- invades beyond Gerota’s fascia
 N1: single LN
 N2: >1 node
 M1: distant metastasis
ROBSON CLASSIFICATION
 STAGE I: TUMOR
WITHIN CAPSULE
 STAGE II: TUMOR
INVASION OF
PERINEPHRIC FAT
 STAGE III: TUMOR
INVOLVES REGIONAL
LN &/OR RV, IVC
 STAGE IV: ADJACENT
ORGANS OR DISTANT
METASTASIS
INVESTIGATIONS
 X-ray abdomen:
 10-20% renal carcinoma show calcification
 IVU:
 solid/cystic
 renal vein/ IVC involvement
 FNAC
 CT:
 most efficient for diagnosis and staging including
secondaries in adrenal/liver
 Angiography
 MRI
Treatment of RCC
 Radical nephrectomy
 kidney, ipsilateral adrenal gland, gerota’s fascia
 treatment of choice for localised disease
 Renal artery embolisation
 Pre-operative shrinkage of large tumours
 controls bleeding
 Vena caval involvement:
 20% renal vein
 5% IVC
 surgical excision gives favourable prognosis
 even tumours extending to atrium can be removed
 NEPHRON Sparing Surgery: Indications
B/L RCC
Solitary Functioning Kidney
Treatment Of Metastatic RCC
 Nephrectomy
 Hormonal Therapy
 Chemotherapy
 Radiation Therapy
 Immunotherapy
Postoperative Surveillance
 Pathological Stage:
T1 N0 M0 – Hist, Exam, Bld test YEARLY
T2N0M0 – H,E,Bt yearly + CXR Yearly
+Abdominal CT 2 yearly
T3abcN0M0 – H,E,Bt 6 mthly + CXR 6
mthly + Abdominal CT yearly
Carcinoma of renal pelvis
 Transitional cell carcinoma
(85%)
 Etiology:
 analgesics: aspirin,
phenacetin
 Balkan nephropathy
 Treatment:
 Nephroureterectomy
 Squamous cell carcinoma:
Chr. Inflam., leukoplakia from
stone. Radiosensitive.
Metastasise early
 Adenocarcinoma
BALKAN NEPHROPATHY
 TRANSITIONAL CELL TUMORS OF
UPPER URINARY TRACT WITH
PRIMARY NEPHROPATHY
 CONSUMING GRAINS STORED IN
DAMP ENVIRONMENT
 CONSERVATIVE SURGERY IN
VIEW OF IMPAIRED OVERALL
RENAL FUNCTION
Carcinoma bladder
 second most common genitourinary
neoplasm
 Male:Female- 3:1
Carcinoma bladder
 Types:
 Transitional cell carcinoma (90%)
 Papillary/exophytic type- most common,
less invasive
 Sessile- more solid and invasive
 Carcinoma in-situ
 Squamous cell carcinoma(7-8%)
 Etiology
 Schistosomiasis
 Bladder calculi
Carcinoma bladder
 Types: (…contd.)
 Adenocarcinoma(1-2%)
 urachal remnants
 Etiology:
 aniline dyes
 Benzidine
 Smoking
 Analgesics, cyclophosphamide, radiation
Carcinoma bladder
 Symptoms:
 Gross painless hematuria (80%)
 Dysuria (20%)
 UTI (30%)
 Metastatic disease(10%)
 Investigations:
 Cystoscopy: for multicentric involvement, biopsy and
staging
 Urinary cytology
 Flow cytometry
 Bladder tumour antigen
 IVU: filling defect
 Pelvic USG, CT scan
Carcinoma bladder
 Staging:
 Ta: non-invasive papillary
cancer
 Tis: carcinoma in-situ
 T1: sub-epithelial tissue
 T2a: superficial muscle
 T2b: deep muscle
 T3a: microscopic perivesical
tissue
 T3b: macroscopic invasion
 T4a: prostate, uterus, vagina
 T4b: pelvic and abdominal wall
 N1: single LN <2cm
 N2: >1LN, <5cm diameter
 N3: >1LN, >5cm diameter
 M1: metastasis
Carcinoma bladder
 Treatment:
 Stage Ta/T1:
 Transurtheral resection of bladder tumour (TURBT)
 Intravesical chemotherapy
 Immunotherapy with intravesical BCG
 Follow up cystoscopy
 BCG refractory: intravesical interferon-alfa 2b
 Stage T2a:
 Radical cystoprostatectomy with pelvic LN dissection
and ileal loop diversion
Carcinoma bladder
 Treatment: (…contd)
 Stage T2b, 3a, N+ve:
 Radical cystectomy with urinary diversion
 with adjuvant chemotherapy- cisplatin
 Metastasis +ve:
 Palliative measures
PROSTATE CANCER
Incidence & etiology
 2nd most common malignancy in male adults
 Chance of acquiring prostate cancer is 15%
during lifetime
 Incidence is 50% greater in blacks than whites,
relatively uncommon in Asians
 Exact etiology is unknown
Incidence & etiology
Associations of prostate cancer
 Genetic influences - risk increased 2 - 3 times if father
or brother has had the disease
 Hormonal factors - some degree of androgen
dependence, does not occur in eunuchs
 Chemical factors -
• workers in rubber , fertilizer, textile industries
• Exposure to cadmium
• Diet high in saturated fat and cigarette smoking
 Other factors -
• More sexually active
• More promiscuous
• Exposure to venereal disease
Prostate cancer
Tumor histology and grading
 >95% of prostate cancer are adenocarcinoma
 Arise from prostatic aciner cell in the periphery
of gland
 BPH develops from inner periurethral tissue
 Sq. cell ca & transitional cell Ca. occur rarely
Diagnosis ….
a) Prostate biopsy or aspiration cytology
- transperineal, transrectal (diagnostic
sensitivity increases with TRUS)
c) Routes of spread -
Lymphatics - external iliac (obturator group),
internal iliac, presacral, supraclavicular
(occasionally via thoracic duct)
Hematogenous - bone, lung , liver , kidney
Diagnosis……
a) Tumor markers -
o PSA (prostate specific antigen) -
• A glycoprotein
• Produced only by prostate cells
• Specific to prostate but not to prostate cancer
• Measured in various ways - PSA density , PSA
velocity, age specific PSA, free PSA
Diagnosis……….
Tumor markers
 PSA measurement for:
 Screening asymptomatic men (along with DRE)
 As an aid in staging prostate cancer
 Follow response to radical prostatectomy and
radiotherapy
 Prostatic acid phosphatase - rarely
used today
Diagnosis…..
a) Bone scan -
• Detects metastatic disease
• Bony metastasis - 80% osteoblastic, 5%
osteolytic, 15% mixed
• Phosphate labelled with technetium99m used
• More sensitive than skeletal radiography (detect
lesions 6 months before apparent on x - rays)
• But less specific than radiography
• Increased uptake seen in arthritis, fractures,
pagets disease, hyperparathyroidism, recent
trauma
Diagnosis….
a) CT scan -
• Assess gross local extension and nodal
metastasis> 2cm in size
• Sensitivity very low (27 - 75%)
o TRUS (transrectal ultrasound)
• Detect small lesion
• Guide biopsy procedure
• Accurate in assessing capsular invasion esp.
seminal vesicle
Diagnosis….
a) Pelvic lymphadenectomy -
• Most accurate staging method available
• Performed in conjunction with radical
retropubic prostatectomy
• Ext. iliac, obturator, internal iliac lymph
node dissected on b/l side for pathology
examination
Diagnosis….
a) Molecular staging -
• PCR amplification for PSA mRNA in blood
or bone marrow
• High false positive and false negative
b) Other newer techniques -
• Endorectal coil MRI
• Monoclonal antibodies
Grading of Tumor
Depends on cytology and /or glandular morphology
2. Mostofi system
3. The M.D.Anderson hospital system
4. Gleason system
 Most widely used today
 Ignores cytologic features
 5 grades of glandular morphology
 Two most prominent glandular patterns are graded 1 - 5
 Sum of these 2 grades will range from 2 - 10
 2 represents - most differentiated
 10 represents –most anaplastic
Staging of prostate cancer
AJCC stage
Primary Tumor
Tx – tumor cannot be assessed
T0 – no evidence of tumor
T1a - tumor found incidentally at TURP (<5% of resected tissue)
T1b - tumor found incidentally at TURP (>5% of resected tissue)
T1c - non palpable tumor identified because of an elevated PSA value
T2a - tumor involves one lobe
T2b - tumor involves both lobes
T3a - extracapsular extension (unilateral/bilateral)
T3b - seminal vesicle involvement
T4 - tumor invades the bladder neck, external sphincter, levator muscle, or
pelvic side wall
- elevated PAP
Staging of prostate cancer
AJCC STAGE
LYMPH NODES
Nx – regional nodes not assessed
N0 – no regional lymph node metastasis
N1 – metastasis to regional (pelvic)
lymph nodes
Metastasis
M1a –metastasis to non regional lymph nodes
M1b –metastasis to bone
M1c –metastasis to other sites
hormone - refractory metastatic disease
Treatment modalities in localized
prostate cancer
1. Radical prostatectomy
- perineal approach
- retropubic approach
- transcoccygeal approach
2. Radiation therapy
• External beam alone
• Interstitial radiation
-I 125 alone with ext. beam radiation
- Pd103 alone or with ext. beam radiation
Treatment modalities in localized
prostate cancer
1. Hormone manipulation
• Bilateral orchiectomy
• Estrogen therapy (diethylstilbestrol)
• Progestational agents (megestrol acetate)
• Luteinizing hormone - releasing hormones
analogs (leuprolide, goserelin)
• Antiandrogens (cyproterone acetate,
flutamide, bicalutamide, nilutamide)
2. Cryosurgery
Approach to treatment by stage of
disease
 Stage T1a -
- no definitive treatment, careful follow up is
appropriate
- within3 months of initial diagnosis of stageT1a,
residual cancer should be ruled out by needle
biopsy, fine - needle aspiration, transurethral
resection
 Stage T1b -
- should be treated aggressively
- either ext. beam radiation or radical
prostatectomy
Approach to treatment by stage of
disease
 Stage T2 -
a) Radical prostatectomy
- ideal candidate if pelvic node involvement is absent
- neoadjuvant hormone therapy is useful to down stage
tumors
- incontinence and impotency are common side effects
e) Ext. beam radiotherapy
- equivalent survival rates to radical prostatectomy at 5 -
10 years following diagnosis
- 6 - 8 weeks required for therapy
- complications - proctitis, cystitis, urethral stricture,
impotence (esp. with pre existing vascular disease)
 Interstitial irradiation (brachytherapy)
- Iodine 125, Pallidium 103
- periodic PSA measurement and DRE are essential for
follow up
Approach to treatment by stage of
disease
 Stage T3
b) Ext. beam radiotherapy
- use of neoadjuvant hormonal therapy with irradiation
are synergistic
c) Brachytherapy with ext. beam radiation with
neoadjuvant hormone
d) Hormonal therapy (androgen deprivation
therapy)
Approach to treatment by stage of
disease
 Stage N+, M+
Androgen deprivation therapy (ADT)
1. Hormonal therapy
2. Bilateral orchiectomy
3. Medical castration
4. Combined androgen blockade -
combined surgical or medical castration
Approach to treatment by stage of
disease
Androgen deprivation therapy (ADT)
2. Anti - androgen
- as monotherapy
- intermittent androgen ablation delay emergence of androgen
refractory clone
- anti androgen withdrawal syndrome
• Decrease PSA level
• Both with non - steroidal and steroidal anti androgen
o Patient counseling - healthy diet, regular weight bearing
exercise, smoking cessation, moderation of alcohol intake
o Bisphosphonates – for clinical evidence of decreased BMD (bone
mass density) or fracture
o Calcium and vit. D
Approach to treatment by stage of
disease
 Hormone refractory prostate cancer
Mechanism of acquiring hormonal resistance
• Androgen receptor (AR) gene amplification
• Altered AR phosphorylation
• AR mutations
• AR reactivation through other signaling pathway
• Altered activity of AR co - regulators
Approach to treatment by stage of
disease
 Hormone refractory prostate cancer
• Chemotherapy -
- docetaxel regime (every 3 week regime)
- previously mitoxantrone and prednisone was used
• Local control -
- external beam radiation therapy
- bone seeking radiopharmaceuticals eg. Strontium89,
samarium 153, rhenium180

• Bisphosphonates and calcium and vit. D

• Pain management - NSAIDS, opioids,
acetamenophen
Future innovations in treatment
of advanced prostate cancer
1. Anti angiogenic therapy
- targets endothelial cells rather than cancer cell, loss of
tumor vasculature
3. Immune base therapy
- passive immunotherapy

(eg. cytokines, antibodies, lymphocytes)

- active immunotherapy (vaccines)

7. Gene therapy
Carcinoma penis –rare
 Etiology:
 Uncircumcised males – chronic smegma irritation
 Human Papilloma Virus
 Dysplastic conditions:
 Leukoplakia
 Balanitis xerotica
 Carcinoma in-situ:
 Erythroplasia of Querat
 Bowen’s disease
 Squamous cell carcinoma (98%): most common.
 verucous carcinoma in 5% cases.
 giant condyloma of Bushcke and Lowenstein
 Basal cell carcinoma
 Metastatic: Genitourinary origin in 75% of cases.
Carcinoma penis
 Spread:
 Lymphatic:
 Prepuce- superficial and deep inguinal LN
 Glans, urethra- deep inguinal and external
iliac LN
 Blood borne:
 lung
 liver
 bone
Carcinoma penis
 Most common site: Glans penis
 Presentation
 Papillary/Ulcerative
 not painful
 Foul smelling discharge
 At presentation 50% have inguinal LN
involvement.
Carcinoma penis
 Staging: Jackson/AJCC
 Primary:
 T1: subepithelial tissue
 T2: invasion of corpus
 T3: invasion of urethra/ prostate
 T4: invasion of adjacent structures
 Lymph nodes:
 N1: single superficial inguinal LN
 N2: multiple or bilateral inguinal LN
 N3: deep inguinal/pelvic LN
 Metastasis:
 M1: distant secondary
Carcinoma penis
 Treatment:
 Partial penectomy: with a disease free margin of 2 cm
 Total penectomy/perineal uretherostomy if involvement of
shaft/base.
 Regional lymphadenectomy
 Radiation
 Iridium brachytherapy
 T1 + palpable adenopathy:
 antibiotics x 3wks
 if adenopathy subsides: follow-up
 if adenopathy remains: LN dissection
 Survival rate (5yr):
 localised: 60-90%
 inguinal LN: 30-50%
 Pelvic: 20%
TESTICULAR AND EXTRAGONADAL
GERM CELL CANCER
Testicular & Extragonadal germ cell
tumour
INCIDENCE:
 Testes cancer is the most common tumour in boys
and men of ages 15 to 35
 1-2 % of all male malignancies
 12% of cancer deaths in patients b/w age 20-35 years
are due to testicular cancer
 H/o cryptorchidism has a 40-70 fold increase in
incidence of testicular cancer, regardless of whether
orchidopexy was done
 Approx. 5% of Germ cell cancer arise in extragonadal
sites, particularly in mediastinum and
retroperitoneum.
CLASSIFICATION OF TESTES
TUMOURS
1. Germ cell tomours
a. Seminoma
- Classic ,Anaplastic , Spermatocytic

d. Embryonal
-adult
-juvenile( yolk –sac tumour)
e. Teratocarcinoma ( teratoma and embryoma)
f. Teratoma
-mature , immature
h. Choriocarcinoma
2. Gonadostromal tumours
a. leydig’s (interstitial) cell
b. Sertoli’s cell
c. Granulosa cell
3. Secondary (metastatic) tumours
Lymphoma , prostate , melanoma , lung
DIAGNOSIS
 Usually present as an asymptomatic
swelling or mass in scrotum
 All mass arising from testes should be
considered carcinoma until proved
otherwise
 Testicular pain is present in only 20 % of
patient
 Gynaecomastia(due to hormone
production) in 5% of cases
 Average delay in diagnosis is 4-6 months
DIAGNOSIS
 Scrotal ultrasound is useful in
differentiating a testicular mass from
epididymitis,hydrocele,spermatocele,
testicular torsion, and inguinal hernia
 Other findings include
lymphadenopathy,abdominal mass, and
chest abnormalities
 Extragonadal tumours often present with
pulmonary complaints (mediastinal
tumours) or back pain or abdominal mass
(retroperitoneal tumours)
DIAGNOSIS & STAGING
 TUMOUR MARKERS
 Primary role of serum tumour markers is not in
staging but in monitoring disease progression or
response to therapy
2. Alpha feto protein (AFP)
 A glycoprotein produced by fetal yolk sac, liver
and GIT
 AFP is not elevated in pure seminoma or
choriocarcinoma
 Metabolic half-life of AFP is 5 days
 False- positive results can occur with hepatoma,
hepatitis, bronchogenic , stomach or pancreatic
cancer
Contd..
 Hcg (human chorionic gonadotropin)
 A glycoprotein produced by
syncytiotrophoblastic cells
 Two subunits-
 Alpha subunit –identical with that of LH
 Beta subunit –unique to hCG
 Serum B-subunit is elevated in 100% of
patients with choriocarcinoma
 Half-life of hCG is 24-36 hours
Contd..
3. Lactic dehydrogenase
 Isoenzyme 1 is elevated in advanced
seminoma & non-seminomatous disease
 Useful for monitoring treatment when
levels of AFP and hCG are normal or
have normalised
2. Placental alkaline phosphatase
 Most sensitive marker for metastatic
seminomatous disease and for relapse
Frequency of elevated tumour
markers in testes cancer

histology Incidenc hCG AFP

e% elevate elevated
d% %
Pure seminoma 35 5 0
Embryonal 20 60 70
Teratocarcinoma 10 60 60
Teratoma 5 25 40
choriocarcinoma 1 100 0
Contd..
 Abdominal CT
 For pre operative staging and metastatic
workup
 It is excellent for nodal involvement
measuring more than 2cm
 Chest CT
 Will identify a small subset of patients
with normal findings on chest x-ray films
but low-level pulmonary metastasis
STAGING OF TESTICULAR CANCER
AJCC Memorial Sloan-Kettering
staging systems

Primary tumour

Tx primary tumour cannot be assessed

T0 no evidence of primary tumour
Tis intratubular tumour(carcinoma in situ) A
T1 limited to testis, including rete testis A
T2 extends beyond tunica albuginea or
shows vascular-lymphatic invasion
T3 invades spermatic cord (with or without
vascular-lymphatic invasion)
T4 invades scrotum(with or without vascular-
lymphatic invasion)
STAGING OF TESTICULAR CANCER
AJCC Memorial Sloan-kettering
stage
Lymph nodes
N1 regional lymph node involvement, <2cm in
diameter and/or 5or fewer nodes involved
B1
N2 regional lymph node involvement, none
>5cm in diameter and/or more than 5 nodes B2
involved
N3 one or more regional lymph nodes involved,
B3 >5cm in diameter
Metastases
M1a nonregional lymph nodes involved or
C
pulmonary metastases
M1b other distant metastases
C
ROUTES OF SPREAD
 Testicular tumours metastasize in predictable, orderly
fashion via retroperitoneal lymphatics
 Tumours of right testes metastasize primarily to
lymph nodes b/w aorta & vena cava below right renal
vein
 Tumours of left side metastasize to pre- aortic & para
aortic lymph nodes on left side
 Right side tumours, unlike left side can cross midline
 Hematogenous spread to lungs may be seen with
choriocarcinoma or bulky nodal disease
MANAGEMENT
1. Testicular tumours
 Radical inguinal orchiectomy is indicated in
most cases as first therapeutic maneuver even
with extensive metastatic disease
 Transscrotal exploration or needle biopsy of
testes is avoided for fear of contaminating the
lymphatic channels of the scrotal skin
2. Extragonadal tumours
 For primary extragonadal seminoma ,
radiotherapy is the primary treatment
 For non-seminomatous tumours, primary
chemotherapy is given with surgical excision of
residual mass
TREATMENT after orchiectomy
 SEMINOMA
 Stage A
 Prophylactic ext. beam radiation to ipsilateral
retroperitoneum (iliac and para aortic nodes
upto the diaphragm)in dose of 25-30 Gy- cure
rate of 90%
 Relapses are salvageable by chemotherapy or
by further radiotherapy to site of relapse
 Other than radiation , treatment option after
radical orchiectomy include surveillance and
adjuvant single agent chemotherapy
TREATMENT after orchiectomy
a. Stage B1 &B2
 Treatment is same as in stage A with addition of
10-15 Gy to site of nodal involvement
b. Stage B3 & C(high –volume disease)
 Radiation therapy has not been very successful
 Combination chemotherapy has now become
the primary therapy for high vol. disease
regardless of histologic type
 Two most commonly used combination are-
 BEP- bleomycin,etoposide,cis-platinum
 VAB-6 –vinblastine,actinomycin
D,bleomycin,cis-platinum,cyclophosphamide
TREATMENT after orchiectomy
 NON-SEMINOMATOUS GERM CELL
TUMOURS
 Shows only little radiosensitivity
 Treatment consists of retroperitoneal lymphadenectomy with
or without combination chemotherapy
b. StageA
 Cure rates avg. 90% in pathologic stage A disease after
RPLND
 Relapse respond well to chemotherapy
 Many centres recommend close surveillance after orchiectomy
without RPLND (watchful waiting)
 Certain high risk pathologic features within orchiectomy
specimen such as presence of embryonal element, vascular &
lymphatic invasion, tunica invasion &epididymal involvement
& absence of yolk sac element argue against surveillance
 Follow up is necessary
TREATMENT after orchiectomy
a. Stage B1 & B2
 RPLND is routinely performed for accurate staging
 Two cycles of combination chemotherapy (platinum
based) following RPLND are given with relapse of 2%
versus 50% without chemotherapy
b. Stage B3 & C( high vol. disease)
 Primary chemotherapy treatment
 Platinum based regimes causes 80% cure
 If CT scan reveals evidence of persistent nodal
disease after chemotherapy, surgical exploration is
used to establish the histologic pattern
 Salvage chemotherapy is necessary for viable
malignancy