Malignant tumors of bladder and their management

1. Dr.P.Viswakumar,M.S
Assistant professor,
Dept of General Surgery,
PSGIMSR
NEOPLASM OF BLADDER

2. Anatomy of Bladder
 The bladder is the most anterior element of the pelvic
viscera.
 The empty bladder is shaped like a three-sided pyramid .
 It has an apex, a base, a superior surface, and two
inferolateral surfaces.
Apex: The apex of the bladder is directed toward the top of
the pubic symphysis.
Base: The base of the bladder is shaped like an inverted
triangle and faces posteroinferiorly.
The inferolateral surfaces of the bladder are cradled between
the levator ani muscles of the pelvic diaphragm and the
adjacent obturator internus muscles above the attachment of
the pelvic diaphragm.

4. Normal Histology
 The mucosal surface of the renal pelvis, ureters,
urinary bladder, and urethra is lined by a
multilayered epithelium.
 The most superficial of which consists of
“umbrella cells”.
 This epithelial lining has historically been called
“transitional epithelium,” it is currently
preferentially referred to as urothelium.
 The wall of the urinary bladder is formed of four
layers: (a) epithelium (urothelium), (b) lamina
propria, (c) muscularis propria, and (d) adventitia
or serosa.

6. Urothelial neoplasm
 The urotheliumof the bladder is traditionally
considered to be lined by transitional cells,
can transform into a variety of benign and
malignant tumors.
 Therefore the list of bladder tumors is long
and includes those derived from the
urotheliumand mesenchyme

7. Benign Tumors of the Bladder
 There are numerous benign tumors of Bladder
Common ones :
1) Epithelial metaplasia,
2) Leukoplakia
3) Inverted papilloma
4) Nephrogenic adenoma
5) Leiomyoma
6) Cystitis cystica
7) Cystitis glandularis.

8. Epithelial metaplasia:
 Focal areas of transformed urotheliumwith
normal nuclear and cellular architecture.
 Located in trigone either squamous or glandular
metaplasia.
 As white flaky knobby appearance in case of
Squamous metaplasia and raised red areas in
case of Glandular ones.
 Appx 40% of women and 5% of men had
squamous metaplasia.
 Usually related to trauma,Infection and surgery.
 No treatment necessary.

9. Leukoplakia
 Similar to squamous metaplasia but addition
to keratin deposition
 Appears as a white flaky substance floating in
the bladder.
 Benign lesion, and no treatment is necessary

10. Inverted Papilloma
 Associated with chronic inflammation or
bladder outlet obstruction and can be located
throughout the bladder but most commonly
on the trigone.
 Inverted papillomas behave in a benign
fashion with only a 1% incidence of tumor
recurrence.
 FISH to differentiate it from Urothelial
malignancy.
 TRUP treatment of choice.

11. Papilloma
 Benign proliferative growth in the bladder
that is composed of delicate stalks lined by
normal-appearing urothelium.
 Papillomas had previously been categorized
as grade 1 Ta tumors of the bladder which
latter classified as non invasive malignancy of
bladder.
 Papillomas may recur, but they do not
progress or invade.

12. Nephrogenic Adenoma
 Rare tumor caused by chronic irritation of the
urothelium.
 Trauma, previous surgery, renal transplantation,
intravesical chemotherapy, stones, catheters, and
infections predispose to it.
 The lesion may be vascular, which explains the
presence of gross hematuria in most cases.
 The most frequent presenting symptom is gross
hematuria, often in conjunction with a urinary tract
infection.
 Transurethral resection and elimination of the
chronic irritation.

13. Cystitis Cystica and
Glandularis
 Common finding in normal bladders, usually
associated with inflammation or chronic obstruction.
 Represent cystic nests that are lined by columnar or
cuboidal cells.
 Cystitis glandularis may develop into or coexist with
intestinal metaplasia, which are benign tumors
characterized by goblet cells that are histologically
similar to colonic epithelium.
 The most common presenting feature of cystitis
cystica or glandularis is irritative voiding symptoms
and hematuria.
 Treatment is transurethral resection and relief of the
obstruction or inflammatory condition.

14. Leiomyoma
 Most common nonepithelial benign tumor of the
bladder composed of benign smooth muscle.
 Most commonly in women of childbearing age and
are histologically similar to leiomyomas of the
uterus.
 Leiomyomas appear as smooth indentations of the
bladder.
 Imaging, especially with magnetic resonance
imaging (MRI), can confirm the diagnosis.
 Surgical resection is required if the leiomyoma is
large or painful.

16. Cancer of Bladder
Topic of discussion for any malignancy
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

17. Cancer of bladder
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

18. Urothelial cancer
Why urothelial cancer is important ?
 Urothelial cancer is a cancer of the environment and
age.
 The incidence and prevalence rates increase with
age, peaking in the 8th decade of life.
 There is a strong association between environmental
toxins and urothelial cancer formation.
 Unfortunately, the incidence rate is rising the fastest
in underdeveloped countries where industrialization
has led to carcinogenic exposure.
 7% of all cancers.

19.  Bladder cancer is the 9th most common
cancer worldwide, with 357,000 cases
recorded in 2002.
 Bladder cancer is the 13th most common
cause of death, accounting for 145,000
deaths worldwide.
 The incidence rate of bladder cancer has been
rising in Asia and Russia because of an
increased prevalence of smoking.

20. Cancer of bladder
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

21. Etiology/Risk factors
Genetic - N-acetyl transferase (NAT) detoxifies
nitrosamines, a known bladder carcinogen.
 Specifically, NAT-2 regulates the rate of acetylation of
compounds such as caffeine, which are related to bladder
cancer formation.
 The slow NAT-2 polymorphism is related to bladder
cancer with an odds ratio of 1.4 compared with the fast
polymorphism.
 Glutathione-S-transferase (GSTM1) conjugates several
reactive chemicals, including arylamines and
nitrosamines.
 The null GSTM1 polymorphism is associated with an
increased bladder risk with a relative risk of 1.5.
 The null GSTM1 and slow NAT-2 lead to high levels of 3-
aminobiphenyl and higher risk of bladder cancer.

22. External risk factors
 The bladder is the main internal organ affected
by occupational carcinogens after skin and Lung.
 The primary culprits are the aromatic amines
that bind to DNA.
 Among the first chemical agents implicated in
the formation of bladder cancer in dye and
rubber workers were benzidine and β-
naphthylamine.
 Other industrial agents implicated in bladder
cancer formation include polycyclic aromatic
hydrocarbons (PAH), diesel exhaust, and paint
substances.

23.  Smoking - Accounts for 60% and 30% of all
urothelial cancers in males and females,
respectively.
 Nutritional factors - moderately higher in
coffee and tea drinkers, but this may be
compounded by smoking or other dietary factors
associated with people who drink coffee or tea.
 Less fluid intake.
 Alcohol : No association has been proved.
 Acetaminopen : Commonly used analgesic-increased
risk of renal and bladder cancer.

24.  Inflammation/ Infection:
1) Schistosoma hematobium – Squamous cell
ca of bladder.
2) HPV.
3) Bacterial – Chronic infection esp with E.Coli
and Pseudomonas.

25.  Radiation exposure : Urothelial cancer
formation after radiation is not age related,
but the latency period is 15 to 30 years.
 Chemotherapy – Only agent
Cyclophosphamide.
 Hereditary

26. Cancer of bladder
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

27. Pathology
 90% of bladder cancers are of urothelial
origin, 5% are squamous cell carcinomas, and
less than 2% are adenocarcinoma or other
variants.
 At initial presentation, 80% of urothelial
tumors are non–muscle invasive.

28. WHO grading of Non invasive
tumors
 Hyperplasia (flat and papillary)
 Reactive atypia
 Atypia of unknown significance
 Urothelial dysplasia (low-grade intraurothelial neoplasia)
 Urothelial carcinoma in situ (high-grade intraurothelial
neoplasia)
 Urothelial papilloma
 Urothelial papilloma, inverted type
 Papillary urothelial neoplasm of low malignant potential
 Noninvasive low-grade papillary urothelial carcinoma
 Noninvasive high-grade papillary urothelial carcinoma

29. WHO grading of Invasive tumors
 Lamina propria invasion
 Muscularis propria (detrusor muscle) invasion

30. Precusor lesions
 Hyperplasia (flat and papillary)
 Reactive atypia
 Atypia of unknown significance
 Urothelial dysplasia
 Urothelial carcinoma in situ
 Urothelial papilloma
 Urothelial papilloma, inverted type
 Papillary urothelial neoplasm of low malignant potential
 Noninvasive low-grade papillary urothelial carcinoma
 Noninvasive high-grade papillary urothelial carcinoma

31. Papilloma Carcinoma in situ

32. Low grade papillary tumor High grade papillary
tumor

33. Cancer of Bladder
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

34. Clinical features
 Often vague
 Gross or microscopic hematuria.(Most common).
 Increased urinary frequency due to irritation of
bladder. (20-30%)
 Less commonly UTI or upper urinary tract
obstruction symptoms in advanced cases.
 Pelvic or bony pain, lower-extremity edema, or
flank pain - In patients with advanced disease.
 Palpable mass on physical examination - Rare in
superficial bladder cancer.

35. Cancer of Bladder
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

36. Investigation and Diagnosis
Urine studies include the following:
 Urinalysis with microscopy
 Urine culture to rule out infection, if suspected
 Voided urinary cytology
 Urinary tumor marker testing
Urinary cytology:
 Standard noninvasive diagnostic method
 Low sensitivity for low-grade and early stage
cancers
 Fluorescence in situ hybridization (FISH) may
improve the accuracy of cytology

37. Investigation and Diagnosis
Cystoscopy
 The primary modality for the diagnosis of bladder
carcinoma
 Permits biopsy and resection of papillary tumors
Upper urinary tract imaging
 Necessary for the hematuria workup
 American Urologic Association Best Practice Policy
recommends computed tomography (CT) scanning of the
abdomen and pelvis with contrast, with preinfusion and
postinfusion phases
 Imaging is ideally performed with CT urography, using
multidetector CT
 Ultrasonography is commonly used, but it may miss
urothelial tumors of the upper tract and small stones

38. Urinary tumor markers
 More than 30 urinary biomarkers have been reported
for use in bladder cancer diagnosis.
 Only few available for commercial use others still in
experimental phase.
 They are
 urine cytology,
 fluorescence in-situ hybridization (FISH),
 nuclear matrix protein (NMP-22),
 BTA STAT, (Bladder tumor Antigen)
 BTA TRAK,
 ImmunoCyt/uCyt+,
 CertNDx, and
 CxBladder.( Uses 5 mRNA markers)

39. Cystoscopy

40. Interpretation of Results
The diagnostic strategy for patients with
negative cystoscopy is as follows:
 Negative urine cytology and FISH - Routine
follow-up
 Negative urine cytology, positive FISH -
Increased frequency of surveillance
 Positive urine cytology, positive or negative
FISH - Cancer until proven otherwise

41. Cancer of bladder
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

42. TNM Staging
 Primary Tumor (T)
 TX Primary tumor cannot be assessed
 T0 No evidence of primary tumor
 Ta Noninvasive papillary carcinoma
 Tis Carcinoma in situ: “flat tumor”
 T1 Tumor invades subepithelial connective tissue
 T2 Tumor invades muscularis propria
 pT2a Tumor invades superficial muscularis propria
 (inner half)
 pT2b Tumor invades deep muscularis propria (outer half)
 T3 Tumor invades perivesical tissue
 pT3a Microscopically
 pT3b Macroscopically (extravesical mass)
 T4 Tumor invades any of the following: prostatic
 stroma, seminal vesicles, uterus, vagina, pelvic wall,
 abdominal wall
 T4a Tumor invades prostatic stroma, uterus, vagina
 T4b Tumor invades pelvic wall, abdominal wall

43. Regional Lymph Nodes (N)
 Regional lymph nodes include both primary and secondary
drainage regions. All other nodes above the aortic
bifurcation are considered distant lymph nodes.
 NX Lymph nodes cannot be assessed
 No lymph node metastasis
 N1 Single regional lymph node metastasis in the true
pelvis (hypogastric, obturator, external iliac, or
presacral lymph node)
 N2 Multiple regional lymph node metastasis in the
true pelvis (hypogastric, obturator, external iliac,
or presacral lymph node metastasis)
 N3 Lymph node metastasis to the common iliac
lymph nodes
Distant Metastasis (M)
 M0 No distant metastasis
 M1 Distant metastasis

45. Treatment Protocol
 Treatment protocols for bladder cancer
includes those of
1) Surgery
2)Chemotherapy,
3)Immunotherapy,
4)Systemic neoadjuvant
5)Adjuvant therapy.

46. Non-muscle invasive bladder
cancer (Ta, Tis, T1)
 Non-muscle invasive bladder cancers are divided
into 3 groups: Ta, Tis, and T1
 Ta are noninvasive papillary lesions confined to the
urotheliumand have not penetrated the basement
membrane.
 Standard treatment for non-muscle invasive bladder
cancer is a complete transurethral resection of the
bladder tumor (TURBT).
 Intravesical chemotherapy is generally used as
prophylactic or adjuvant therapy after complete
endoscopic resection
 It is rarely used as therapy to eradicate residual
disease that could not be completely resected.

47. Postoperataive adjuvant intravesical chemotherapy
for non-muscle invasive bladder cancer[1, 2] :
 One postoperative intravesical dose (within 24h,
but usually immediately after resection) has
been shown to reduce recurrence, but not
progression, of disease
 Mitomycin 40 mg in 20 mL sterile water or
 Epirubicin 80 mg in 40 mL sterile water or
 Thiotepa 30 mg in 15 mL sterile water or
 Doxorubicin 50 mg in 20 mL sterile water

48. High grade or T1 disease:
 Management of T1 tumors with TURBT is generally
not adequate enough; use of intravesical bacillus
Calmette-Guerin (BCG) after TURBT is
recommended
Intravesical adjuvant immunotherapy for non-muscle
invasive bladder cancer[1, 3, 2] :
 BCG 81 mg (TheraCys) or 50 mg (TICE BCG) in 50
mL sterile saline instilled into the bladder through a
catheter and held for 2h; it is instilled into the
bladder weekly for 6wk
 Maintenance therapy: 81 mg intravesically given on
Days 1, 8, and 15 of Months 3, 6, 12, 18, 24, and 36
after initiation

49. Muscle invasive bladder cancer
The treatment of muscle-invasive bladder
cancer is as follows:
 Radical cystoprostatectomy in men
 Anterior pelvic exenteration in women
 Bilateral pelvic lymphadenectomy (PLND),
standard or extended
 Creation of a urinary diversion
 Neoadjuvant chemotherapy - May improve
cancer-specific survival

50. Chemotherapeutic regimens for metastatic
bladder cancer include the following:
 Methotrexate, vinblastine, doxorubicin
(Adriamycin), and cisplatin (MVAC)
 Gemcitabine and cisplatin (GC)

51. Cancer of bladder
1) Incidence and prevalence.
2) Etiology/ Risk factors.
3) Pathology.
4) Clinical features.
5) Investigation and diagnosis.
6) Staging and Management.
7) Prognosis

52. Prognosis
 The recurrence rate for superficial TCC of the
bladder is high. As many as 80% of patients
have at least 1 recurrence.
 The most significant prognostic factors for
bladder cancer are grade, depth of invasion,
and the presence of CIS.
 In patients undergoing radical cystectomy for
muscle-invasive bladder cancer, the presence
of nodal involvement is the most important
prognostic factor.

53. Prognosis
 Non–muscle invasive bladder cancer has a good
prognosis, with 5-year survival rates of 82-100%. The
5-year survival rate decreases with increasing stage,
as follows:
 Ta, T1, CIS – 82-100%
 T2 – 63-83%
 T3a – 67-71%
 T3b – 17-57%
 T4 – 0-22%
 Prognosis for patients with metastatic urothelial
cancer is poor, with only 5-10% of patients living 2
years after diagnosis.

54. Other types of Bladder
Cancer
Squamous Cell Ca:
 The second most common cell type associated with
bladder cancer in industrialized countries.
 However, SCC is the most common form of bladder
cancer, accounting for 75% of cases in developing
nations.
 In developing nations, SCC is often associated with
bladder infection by Schistosoma haematobium.
 The overall 5-year survival rate was 56% for pT1 and
68% for pT2 tumors. However, the 5-year survival
rate for pT3 and pT4 tumors was only 19%

55. Other types of Bladder
Cancer
 Approximately 2% of bladder cancers are
adenocarcinomas.
 Nonurothelial primary bladder tumors are
extremely rare and may include small cell
carcinoma, carcinosarcoma, primary
lymphoma, and sarcoma.
 Small cell carcinoma of the urinary bladder
accounts for only 0.3-0.7% of all bladder
tumors.

56. Conclusion
 Urinary tract is lined by multilayered epithelium called
‘Urothelium’
 Urothelium can transform into wide variety benign and
malignant neoplasms.
 Most common malignancy of bladder is Urothelial carcinoma
followed by squamous cell carcinoma.
 It is a common malignancy due to occupation hazard for those
working in chemical esp., Dyeing industry.
 Genetic factors such NAT and Glutathione deficiency states and
smokers are more prone for urothelial cancer.
 Schistasomiasis leading cause of SCC in developing world.
 80% cases at presentation are non muscle invasive
 Hematuria is the most common presenting complaint

57. Conclusion
 Cystoscopy, urine tumor markers,USG and CT
abdomen are the investigations used in diagnosis
and staging of the tumor.
 Muscle non invasive cancers include Ta,Tis and T1
stage tumors.
 Such cases treated with TURBT and intravesicle
chemotherapy depending on grade
 Others are treated with radical surgery and follow up
adjuvant chemotherapy.
 Prognosis of superfiscial bladder cancer is good
touching 80-100% 5 yr survival rate and prognosis
worsens with increasing depth of invasion.