Principles of Renal Cell Carcinoma and Bladder Cancer

1. Renal Cell Carcinoma
Bladder Carcinomas
DR. Jwan Ali Ahmed AlSofi

2. Introduction and differential
diagnosis
65 year male patient present with red color urine , no pain , no fever
, no lut sx , no history of trauma, no history of stone , he denied
eating any beet or blackberry , no any recent medications , no
history of bleeding tendency -ve .
Past medical and past surgical history .
What is your differential diagnosis:
1. Renal cell carcinoma
2. Bladder urothelial cancer
3. Renal pelvic urothelial cancer
4. Benign renal tumor
in this lecture we will discuss renal cell ca and urothelial bladder
cancer in detail .

3. ADENOCARCINOMA OF THE
KIDNEY
(RCC)

4. Introduction
Roughly 2.8% of adult cancers.
Constitutes approximately 85% of all
primary malignant renal tumors.
 RCC occurs most commonly in the
fifth to sixth decade.
 Has a male–female ratio of 2:1.
The incidence of renal cancer may
vary based on race, with black men
demonstrating a higher incidence.
Asians appear to have the lowest
incidence of RCC.

5. 1. Cigarette smoking- 2x increase in risk for the development
of RCC in smokers
2. Occupational exposures - asbestos, solvents, and
cadmium
3. Hereditary RCC - RCC occurs in two forms, inherited and
sporadic
4. Acquired cystic disease of the kidneys
- is a well-recognized entity of multiple bilateral cysts in the native kidneys
of uremic patients
- Most RCC cases have been described in patients undergoing
hemodialysis
5. Hypertension.

6. PATHOLOGY
RCC originates from the proximal renal
tubular epithelium,
RCCs originate in the cortex
 tend to grow out into perinephric tissue,
causing the characteristic bulge or
mass effect that aids in their detection
by diagnostic imaging studies.
Grossly, the tumor is characteristically
yellow to orange because of the
abundance of lipids, particularly in the
clear cell type.
RCCs do not have true capsules but
may have a pseudocapsule of compressed
renal parenchyma, fibrous tissue, and
inflammatory cells.

7. PATHOLOGY
• RCCs are classified into one of the
following histologic subtypes:
1. conventional clear cell,
2. papillary (chromophilic),
3. chromophobe,
4. collecting duct,
5. neuroendocrine,
6. unclassified.

8. Pathogenesis
• RCCs are vascular tumors that tend to spread either
1. by direct invasion through the renal capsule into perinephric
fat and adjacent visceral structures
2. or by direct extension into the renal vein.
• Approximately 25–30% of patients have evidence of
metastatic disease at presentation.
• The most common site of distant metastases is the lung.
• However, liver, bone (osteolytic), ipsilateral adjacent
lymph nodes and adrenal gland, brain, the opposite
kidney, and subcutaneous tissue are frequent sites of
disease spread.

9. Paraneoplastic Syndromes
1. Erythrocytosis.
– RCC is the most common cause of paraneoplastic erythrocytosis,
– 3–10% of patients with RCC
– In patients with RCC, the elevated erythrocyte mass is physiologically
inappropriate
– may result either from enhanced production of erythropoietin from the tumor
or as a consequence of regional renal hypoxia promoting erythropoietin
production from non-neoplastic renal tissue.
2. Hypercalcemia
– 20% of patients with RCC
– may be due to production of a parathyroid hormone-related peptide that
mimics the function of parathyroid hormone or other humoral factors such as
osteoclast-activating factor, TNF, and TGF-alpha.
3. Hypertension
– 40% of patients with RCC
– renin production by the neoplasm has been documented in 37%.
– The excess renin and hypertension associated with RCC are typically
refractory to antihypertensive therapy but may respond after nephrectomy.

10. Paraneoplastic Syndromes
4. Stauffer’s syndrome
– a reversible syndrome of hepatic dysfunction in the absence of hepatic
metastases associated with RCC.
– Occurs in the absence of hepatic metastasis
– Hepatic function abnormalities include:- ↑ alkaline phosphatase and bilirubin,
hypoalbuminemia, prolonged prothrombin time, and hypergammaglobulinemia.
– fever, fatigue, and weight loss
– typically resolves after nephrectomy
– It may be due to overproduction of granulocyte-macrophage colony stimulating
factor by the tumor.
•A paraneoplastic syndrome present at the time of disease diagnosis
does not, in and of itself, confer a poor prognosis.
•However, patients whose paraneoplastic metabolic disturbances fail
to normalize after nephrectomy (suggesting the presence of clinically
undetectable metastatic disease) have very poor prognoses .

11. PRESENTATION
 Symptoms and Signs.
 With the routine use of CT scanning for evaluation of nonspecific findings,
asymptomatic renal tumors are increasingly detected incidentally (>50%).
 The classically described triad of gross hematuria, flank pain, and a
palpable mass occurs in only 7–10% of patients and is frequently a
manifestation of advanced disease.
 Patients may also present with hematuria, dyspnea, cough, and bone pain that
are typically symptoms secondary to metastases.

12. • Historically, RCC was known as the
internist’s tumour, because of its
presentation with the classical triad.

13. CLINICAL FINDINGS
1. Loin mass.
2. Rapid developing
varicocele due to
compression on
gonadal vein.

14. LABORATORY FINDINGS
• Laboratory abnormalities associated with the various RCC
paraneoplastic syndromes,
• Anemia,
– Occurs in 30% of RCC patients.
– The anemia typically is not secondary to blood loss or hemolysis
– is commonly normochromic.
– The serum iron and total iron-binding capacity are usually low, as in the
anemia of chronic disease.
– Iron therapy is usually ineffective;
– surgical removal of early-stage tumors usually leads to physiologic correction
of the anemia.
– The potential role of recombinant erythropoietin for patients with unresectable
disease repre-sents a potential, but untested, option.
• Hematuria
– Gross or microscopic hematuria can be seen in up to 60% of patients presenting with
RCC.
• ↑ ESR
– 75% in RCC

15. IMAGING
• US examination is a noninvasive,
relatively inexpensive technique
able to further delineate a renal
mass.
• It is approximately 98%
accurate in distinguishing simple
cysts from solid lesions.
• Strict ultrasonographic criteria
for a simple cyst include:
1. through transmission,
2. a well-circumscribed mass
3. without internal echoes,
4. adequate visualization of a strong
posterior wall.

16. CT SCAN
CT scan is more sensitive than US or IVU for
detection of renal masses and now is consider gold
standard .
 method of choice in staging of tumor .
A typical finding of RCC on CT is :
mass that becomes enhanced with the use of intravenous
contrast media .

17. MRI
 MRI is equivalent to CT for staging of RCC

18. RADIONUCLIDE SCAN
 Imaging Determination
of metastases to bones
is most accurate by
radionuclide bone scan,
although the study is
nonspecific and requires
confirmation with bone
x-rays of identified
abnormalities to verify
the presence of the
typical osteolytic
lesions.

19. CXR
• Detect lung
secondary.
• Cannon ball.

20. RENAL BIOPSY
 Needle biopsy of renal
masses is not
recommended, since the
result may be misleading
and complications include
hemorrhage and seeding
of the biopsy tract.
 Indication renal mass
biopsy:-
1. Metastatic malignant
disease .
2.Renal lymphoma .
3.Renal abscess .

21. TUMOR STAGE

23. DIFFERENTIAL DIAGNOSIS

24. TREATMENT

25. 1- LOCALIZEDDISEASE
- RADICAL NEPHRECTOMY -
 0pen Radical nephrectomies or Laparoscopic or robotic
radical nephrectomy are the primary treatments for localized RCC.
 Various open incisions provide optimal access for the radical
nephrectomy, including an anterior subcostal (unilateral chevron) or
thoracoabdominal incision, and, occasionally, a midline incision or the
classic flank incision.
 The likelihood of local recurrence after radical nephrectomy is 2–3%

27. - PARTIAL NEPHRECTOMY-
aka - Nephron-sparing surgery-
 Partial nephrectomy and wedge resection with an adequate margin
of normal parenchyma is considered standard primary surgical
therapy for patients with tumors <7 cm in size, even in the
presence of a normal contralateral kidney.
 Local recurrence of tumor in the same kidney ranges from 0% to
10%.
 INDICATION
1. T1 tumor.
2. Bilateral RCC .
3. Single kidney .
 Complication
( bleeding , leak , injury to surrounding structure ).

28. 2- ADVANCED DISEASE
 Approximately 30% of patients with RCC will present with advanced
disease.
 Metastatic RCC has a variable natural history, with 5-year survival
rates typically <10%
A. Surgery—radical nephrectomy used as a palliative procedure in
the setting of metastatic disease for managing patients with severe
hemorrhage or unremitting pain.
B. Radiation therapy—Radiation therapy is an important method
in the palliation of patients with metastatic RCC. Despite the belief
that RCC is a relatively radioresistant tumor, effective palliation of
metastatic disease to the brain, bone, and lungs is reported in up to
two-thirds of patients.
C. Chemotherapy- Chemo-resistant.
D. Biologic response modifiers ( immune therapy).

29.  RCC the most common primary renal malignant tumor , mostly occur in
5th- 6th decade
 Mostly diagnosed incidentally , classical triad of loin mass , pain ,
hematuria only present in 7-10% and may indicate advanced disease
 CT scan is gold standard diagnostic modality
 Radical nephrectomy is primary surgical treatment for localized RCC ,
partial nephrectomy indicated for T1 RCC, bilateral RCC, RCC in single
kidney.

31. BLADDER CANCER

32.  Incidence Bladder cancer is the second most
common cancer of the genitourinary tract .
 Men 2.5 times more likely than women to develop
the disease and die from it.
 Age increases risk; it is most commonly diagnosed
in the eighth decade and is rare in those <50
years of age.
 Race: Black people have a lower incidence than
that of White people, but inexplicably they
appear to carry a poorer prognosis.
 The average age at diagnosis is 65 years. At that
time:
 75% of bladder cancers are localized to the bladder
 25% have spread to regional lymph nodes or distant sites

33. RISK FACTORS
1. Cigarette smoking accounts for 65% of cases in men and 20–30% in women.
the association appears to be dose related.
2. Occupational exposure accounts for 15–35% of cases in men and 1–6% in
women. .
3. Patients who have received cyclophosphamide (Cytoxan) for the management
of various malignant diseases are also at increased risk .
4. Ingestion of artificial sweeteners has been proposed to be a risk factor,
but several studies have failed to confirm any association .
5. Physical trauma to the urothelium induced by infection, instrumentation,
and calculi increases the risk of malignancy
6. Pelvic radiotherapy for other malignancies such as prostate, rectal or
cervical cancer
7. Chronic inflammation of bladder mucosa: bladder stones, long-term
catheters, and the ova of
8. Schistosoma haematobium (bilharziasis) are implicated in development of
squamous cell carcinoma of the bladder.
9. genetic etiology The most common cytogenetic abnormality is loss of
chromosomes 9p, 9q, 11p 13q, and 17q

34. HISTOPATHOLOGY
 98% of all bladder cancers are epithelial malignancies, with the
predominant majority being transitional cell carcinomas
(TCCs) 90% .
 About 5% are adenocarcinomas or squamous cell carcinomas.
1. These tumors most commonly appear as papillary this group is usually
superficial in nature,
2. exophytic lesions less commonly, they may be sessile or ulcerated ,
sessile growths. are often invasive.
3. CIS (carcinoma insitu ) is recognizable as flat, anaplastic epithelium.

35. Nontransitional Cell Carcinomas
1. Adenocarcinoma—Adenocarcinomas account for <2% of all bladder cancers.
Primary adenocarcinomas of the bladder may be preceded by cystitis and
metaplasia.
2. Squamous cell carcinoma—Squamous cell carcinoma accounts for between 5%
and 10% of all bladder cancers in the United States and is often associated here
with a history of chronic infection, vesical calculi, or chronic catheter use
may also be associated with bilharzial infection owing to Schistosoma haematobium.
3. Rare Epithelial and Nonepithelial Cancers
Rare epithelial carcinomas identified in the bladder include villous adenomas,
carcinoid tumors, carcinosarcomas, and melanomas.
Rare nonepithelial cancers of the urinary bladder include pheochromocytomas,
lymphomas, choriocarcinomas, and various mesenchymal tumors (hemangioma,
osteogenic sarcoma, and myosarcoma)

36. CLINICAL FINDINGS
Symptoms
Hematuria
 is the presenting symptom in 85–90% of patients with bladder cancer.
 Painless
 It may be gross or microscopic – usually gross-
 intermittent rather than constant.
 Irritative voiding symptoms
 In a smaller percentage of patients, it is accompanied by symptoms of
vesical irritability: frequency, urgency, and dysuria.
 Irritative voiding symptoms seem to be more common in patients with
diffuse CIS.
Symptoms of advanced disease include bone pain from
bone metastases or flank pain from retroperitoneal
metastases or ureteral obstruction.

37. SIGNS
As most patients have superficial localized disease, signs are generally
absent.
General examination may reveal pallor, indicating anemia due to chronic
renal impairment or blood loss in more advanced disease.
Abdominal examination may reveal a suprapubic mass in the case of locally
advanced disease.
Digital rectal examination may reveal a mass above or involving the
prostate.
If bladder not mobile that suggests fixation of tumor to adjacent
structures by direct invasion.
Hepatomegaly and supraclavicular lymphadenopathy are signs of
metastatic disease.
Lymphedema from occlusive pelvic lymphadenopathy may be seen
occasionally.
Patients may also present with back pain or pathologic fracture from
bony metastases.
On rare occasions, metastases can occur in unusual sites such as the skin
presenting as painful nodules with ulceration

38. LABORATORY FINDINGS
1. Routine testing
• The most common laboratory abnormality is
hematuria.
• It may be accompanied by pyuria, which on
occasion may result from concomitant urinary
tract infection.
• Azotemia may be noted in patients with
ureteral occlusion owing to the primary bladder
tumor or lymphadenopathy.
• Anemia may be a presenting symptom owing
to chronic blood loss, or replacement of the
bone marrow with
metastatic disease.
3. Tumor markers
• To overcome the shortcomings of urinary
cytology such as the low sensitivity for low-
grade superficial tumors and inter-observer
variability.
• These tests have been demonstrated to
enhance detection of bladder cancer when used
either individually or in combination with
cytology e.g. the bladder tumor antigen (BTA)
NMP22 assay ImmunoCyt and UroVysion.
2. Urinary cytology
• Exfoliated cells from normal and
neoplastic urothelium can be readily
identified in voided urine.
• Large quantities can be obtained by gentle
irrigation of the bladder through catheter
or cystoscopy or by direct voiding.
• Cytological examination maybe especially
useful in detecting cancer in
asymptomatic patients and a the
detection rate is higher in high grade
tumors and CIS but not as much low grade
superficial tumors.

39. 1. Increase in nuclear-to-cytoplasmic ratio
2. Multiple atypia and mitoses
3. Increase in number of nucleoli

40. IMAGING
 Although bladder cancers may be detected by
various imaging techniques, their presence is
confirmed by cystoscopy and biopsy.
 Imaging is therefore used to:-
1. evaluate the upper urinary tract and, when
infiltrating bladder tumors are detected,
2. to assess the depth of muscle wall infiltration
3. the presence of regional or distant metastases.

41. • Superficial (Ta, Tis) bladder cancers
staged with a properly performed TUR and
examination under anesthesia do not
require additional imaging of the bladder
or pelvic organs.

42. Intravenous urography
• Intravenous urography used to
be one of the most common
imaging tests for the evaluation
of hematuria.
• However, it has virtually been
replaced by (CT) urography,
which is more accurate, for
evaluation of the entire
abdominal cavity, renal
parenchyma, and ureters in
patients with hematuria.

43. CT & MRI
• Both CT and MRI have
been used to:-
1. characterize the extent
of bladder wall
invasion
2. detect enlarged pelvic
lymph nodes.

44. chest x-ray / radionuclide
bone scan
• Because invasive
bladder cancers may
metastasize to the
lung or bones,
staging of advanced
lesions is completed
with chest x-ray and
radionuclide bone
scan.

45. CYSTOURETHROSCOPYANDTUMOR RESECTION
• The diagnosis and initial staging of bladder cancer is made by
cystoscopy and transurethral resection (TUR).
• Cystoscopy can be done with either flexible or rigid
instruments, although the former is associated with less discomfort
and only requires local anesthesia.
• Superficial, low-grade tumors usually appear as single or multiple
papillary lesions.

46. Higher grade lesions are larger and
sessile.
CIS may appear as flat areas of
erythema and mucosal irregularity.
• The objectives are
1. tumor diagnosis,
2. assessment of the degree of bladder
wall invasion (staging),
3. complete excision of the low-stage
lesions amenable to such treatment.

47. TURBT

48. TNM STAGING
• Simple staging is helpful in
determining treatment and
prognosis into
1. Superficial disease ( no
muscle-invasion )
(Ta , T1 , CIS )
2. Muscle-invasive disease
T2 and above.

50. TREATMENT SELECTION
 Superficial disease Ta , T1 , CIS
1. Endoscopic resection (TURBT) is the preferred treatment
for superficial disease (i.e. Ta and some T1 and Tis).
2. Intravesical immunotherapy (BCG) or chemotherapy can be
used to prevent recurrence & progression.
3. These patients require permanent, repeated urinary cytology
and endoscopic review to monitor progress.

51. • Most agents are administered weekly for 6 weeks except when being
used prophylactically where a single dose is administered immediately
following TUR.
• Maintenance therapy (ie, monthly or bimonthly intravesical therapy)
may decrease recurrence rates further.
• Local toxicity is relatively common—primarily irritative voiding
symptoms—
• Systemic toxicity is rare because of the limited absorption of drugs
across the lumen of the bladder.

52.  Muscle-invasive disease T2 and above
1. Deeper tumours extending into the detrusor muscle need surgical
resection with Radical Cystectomy and Urinary Diversion of
ureters to an ileal conduit or in some circumstances to a neobladder
created from a bowel segment.
2.Trimodality therapy:- Endoscopic resection of bladder
tumor with a subsequent combination of Radiotherapy
and Chemoherapy.
– May be used as primary therapy in muscle-invasive disease with or
without chemotherapy,
– is more often reserved for those unfit for radical surgery.
– Chemoherapy might be helpful for metastatic disease.

54. - Bladder cancer is the second most common cancer of the genitourinary tract.
- Age increases risk; it is most commonly diagnosed in the eighth decade and is rare in
those <50 years of age.
- Cigarette smoking accounts for 65% of cases in men and 20–30% in women.
- transitional cell carcinomas (TCCs) 90% . About 5% are adenocarcinomas or
squamous cell carcinomas.
- Hematuria is the presenting symptom in 85–90% of patients with bladder cancer
- Endoscopic resection (TURBT) is the preferred treatment for superficial disease
(i.e. Taand some T1 and Tis).
- Deeper tumours extending into the detrusor muscle need surgical resection with
Radical Cystectomy and Urinary Diversion

56. REMEMBER
 Haematuria in RCC  painful
 Haematuria in Bladder Ca  painless, gross,
intermittent.
 How you differentiate between ureteric stone
and RCC since both may be associated with
haematuria + ureteric colick?
-Uretric stone  First there is ureteric colick then
haematuria occurs.
-RCC  First there is haematuria followed by the ureteric
colick.
(( Haematuria  clot  ureteric obstruction  ureteric
colick))

57. All the following are true about renal cell cancer RCC except:
a) RCC occurs most commonly in the fifth to sixth decade .
b) The classical triad of gross hematuria, flank pain, and a
palpable mass occurred in most of cases.
c) Approximately 25–30% of patients have evidence of
metastatic disease at presentation.
d) RCC originates from the proximal renal tubular epithelium .
e) Acquired cystic disease of the kidneys in uremic patients is
risk factor.
Answer: b

58. Which point is wrong about urothelial bladder cancer :
a) Is the second most common cancer of the genitourinary
tract .
b) Cigarette smoking depend on duration but not intensity of
smoking .
c) Irritative voiding symptoms seem to be more common in
patients with diffuse CIS .
d) CIS (carcinoma in situ) is recognizable as flat, anaplastic
epithelium and very aggressive.
e) Most patients have superficial localized disease, signs are
generally absent .
Answer: b

59. 65 year male patient present with red color urine , rt
loin pain, no fever, no lut sx, no history of trauma, no
history of stone, he deny eating any beet or blackberry,
any recent medications, no history of bleeding
tendency, on exam palpable rt loin mass.
All the following action you have to do except :
a) ESR
b) Chest x-ray
c) No need to do renal biopsy
d) Liver function test
e) Ct-scan of abdomen and pelvis native film
Answer: e - CT scan should be with contrast

60. Which of the following is true about urothelial bladder
cancer :
a) Bladder cancers presence is confirmed by CT scan.
b) Tumor markers very specific for bladder cancer.
c) The diagnosis and initial staging of bladder cancer is
made by cystoscopy and transurethral resection (TUR).
d) Transitional Cell Carcinoma Approximately 10% of all
bladder cancers.
e) Muscle invasive bladder cancer include T1 , T2 and T3.
Answer: c

61. All the following true about Renal cell cancer except :
a) We can very easily differentiate between benign and
malignant renal tumor radiologically.
b) Renal cell carcinoma is radio and chemoresistant.
c) Ct scan both native and contrast is gold stander in
management RCC.
d) The only potentially curative therapy available for RCC
patients is surgical removal.
e) Renal cell carcinoma is the most lethal urological
tumor.
Answer: a

62. All the following true about bladder Cancer except :
a) Most common presentation painful gross hematuria.
b) Urine Cytology of exfoliated cells very useful for
detection of bladder cancer.
c) Bilharzial infection owing to Schistosoma haematobium
is risk factor for bladder tumor.
d) Non muscle invasive managed by TURBT and
intravesical chemotherapy.
e) Radical Cystectomy and Urinary Diversion in case T2
bladder cancer.
Answer: a – it is gross, painless, and intermittent

63. Thanks