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Urology Residency Flash Cards > Bladder Tumors > Flashcards

Bladder Tumors Flashcards

Wieders Review

1
Q

What are the types of primary bladder tumors?

A
  1. Urothelial CA (TCC) (more than 90%)

Non-Urothelial:

  1. Squamous cell carcinoma (5%)
  2. Adenocarcinoma (1%)
  3. Small cell carcinoma
  4. Rhabdomyosarcoma (most commonly seen in children)
  5. Bladder pheochromocytoma
  6. Bladder lymphoma
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2
Q

Where do secondary (metastatic to bladder) bladder cancers come from in order of most common to least?

A

melanoma > colon > prostate > lung > breast

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3
Q

List 7 risk factors for bladder cancer?

A
  1. Smoking (carcinogenic ingredient is aromatic amines)
  2. Chronic cystitis (increased risk of SCC) ( causes = catheters, UTI’s, chronic bladder stones, schistosoma haematobium (bilharzial) infection.
  3. Chemical exposures (aromatic amines) - professions (hairdressers, dye workers, leather workers, painters, dry cleaners)
  4. Phenacitin
  5. Radiation to the bladder
  6. Pioglitazone (diabetic medication)
  7. Cyclophosphamide (chemotherapeutic)
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4
Q

What can cyclophosphamide cause and through what mechanism? How can you prevent this?

A

Hemorrhagic cystitis and increased risk of bladder cancer. Causes this via its metabolite - ACROLEIN.

MESNA should be given with cyclophosphamide as it will bind to ACROLEIN and facilitate its excretion.

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5
Q

What is a nephrogenic adenoma and what should you do about it?

A

A rare benign lesion in the bladder that is a metaplastic response to trauma or inflammation. Treat with transurethral resection and long term antibiotics (one year). They have a high recurrence rate.

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6
Q

What are the histological findings of a nephrogenic adenoma?

A

A single layer of cuboidal epithelium. Classic microscopic finding is HOBNAIL epithelial cells.

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7
Q

How does a nephrogenic adenoma present?

A

Dysuria, frequency and history of UTI

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8
Q

How do bladder tumors present?

A
  1. Most common is hematuria (microscopic or gross)
  2. Irritative LUTS (frequency, urgency, and dysuria) usually associated with high grade tumors or CIS
  3. Patients with advanced cancer may have bone pain (mets) or flank pain (ureteral obstruction, retroperitoneal mets)
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9
Q

How do you work up a bladder tumor?

A
  1. History and physical exam
  2. Cystoscopy
  3. CT urogram or KUB U/S
    4 Urinary cytology
  4. If there is high metastatic risk - order: LFT’s CT chest/abdomen/pelvis, bone scan if elevate ALP or bony pain
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10
Q

How do you diagnosis bladder cancer?

A

Transurethral resection of bladder tumor (TURBT)

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11
Q

What maneuver is important to perform in the clinical staging of bladder cancer?

A

Bimanual exam - clinical staging is based on bimanual exam AFTER turbt

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12
Q

What should be the goals of a successful TURBT?

A
  1. Remove enough tissue to determine depth of invasion
  2. Completely resect all visible tumor
  3. Do not perforate bladder
  4. Obtain good hemostasis following resection
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13
Q

When should you NOT resect all the tumor on TURBT?

A
  1. Extensive CIS is present - extensive resection or fulguration can lead to a contracted bladder
  2. The tumor appears unresectable via a transurethral approach
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14
Q

Who requires a repeat TURBT and why?

A

Anyone with TaHG or T1HG on initial resection - second TURBT finds residual disease in 25% of resections and upstages the pathology in 30% - ESPECIALLY if MUSCULARIS PROPRIA is absent.

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15
Q

How does fluorescence cystoscopy with hexaaminoleuvulinic acid (HALA) (heme precursor) work? How do you use it? Who should it be used in?

A
  1. HALA absorbed into urothelial cells where it is converted to protoporphyrin IX (PPIX). PPIX fluoresces under blue light and accumulates in malignant cells hence bladder cancer fluoresces
  2. Instillation intravesically
  3. May help improve detection of UC (especially CIS) but inflammation can generate high false positive rate.
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16
Q

What is an alternative enhanced visualization method to improve detection of bladder tumors that does NOT require any intravesical bladder instillation?

A

Narrow band imaging (NBI) - filters white light into blue and green regions. Blue and green absorbed by hemoglobin enhancing visualization of highly vascular tissues.

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17
Q

What is the obturator reflex?

A

Obturator reflex - obturator nerve runs near lateral walls of bladder. Resection in this area can stimulate nerve resulting in sudden leg adduction and resultant bladder perforation.

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18
Q

How can you avoid the obturator reflex?

A
  1. General anaesthesia with neuromuscular blockade (paralysis)
  2. Avoiding bladder over distension (may keep the nerves further away)
  3. Lowering the resection current
  4. Obturator nerve block with local anaesthesia
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19
Q

What are methods to reduce the risk of bladder perforation when performing a TURBT?

A
  1. Use caution when resecting tumors in a diverticulum (has no muscularis layer)
  2. Avoid the obturator reflex
  3. Avoid bladder overdistension
  4. Avoid deep resection of low grade tumors that seem low grade and superficial
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20
Q

What should you do about tumors at the ureteral orifice?

A
  1. Avoid extensive cauterization at the UO - can cause a distal ureteral stricture. If it is required use minimal low-current focal pinpoint cautery
  2. Cutting current over the UO is unlikely to cause postoperative UO obstruction secondary to stricture or edema. If patient has solitary kidney can consider placing a stent.
  3. Perform a renal scan, urogram, or U/S 3-6 weeks after resection over UO to ensure no obstruction.
  4. Resection of the UO can cause VUR. In patients with known VUR and UC there is 15-22x increased risk of UTUC hence upper tract surveillance should be initiated
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21
Q

Is it okay to perform a TURBT and TURP in the same operation?

A

Yes. Simultaneous TURP + TURBT for Ta or T1 bladder CA does not appear to increase the risk of subsequently developing UC in the prostatic urethra compared to TURBT alone.

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22
Q

What are the indications for a prostatic urethra biopsy?

A
  1. Multifocal UC of the bladder
  2. Tumor at bladder neck
  3. CIS of the bladder
  4. A visible abnormality suspicious for tumor in the prostatic urethra
  5. Unexplained positive urine tumor marker
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23
Q

If prostate invasion suspected how do you take the biopsies?

A

loop resection at 5 and 7 o’clock. If invasion not suspected cold cup biopsies can be taken.

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24
Q

What are the indications for random bladder biopsies?

A
  1. Planned partial cystectomy
  2. Abnormal urine tumor marker without tumor in the bladder
  3. Urine cytology shows high grade cells but biopsy shows low grade UC.
  4. After intravesical therapy for CIS to evaluate for complete response.
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25
Q

How do you grade bladder cancer?

A
  1. PUNLMP (papillary urothelial neoplasm of low malignant potential)
  2. Low grade (well differentiated)
  3. High grade (poorly differentiated)
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26
Q

What is the T-staging for bladder CA (AJCC 2010)?

A 
Tx - cannot be assessed
T0 - no evidence of cancer
Ta - superficial bladder cancer
Tis - carcinoma in situ
T1 - invasive into lamina propria 
T2 - invasive into muscularis propria
        T2a - invasive into inner half 
        T2b - invasive into outer half 
T3 - invasive into perivesical fat
       T3a - microscopic invasion
       T3b - macroscopic invasion
T4 - Tumor invades into an adjacent structure (prostatic stroma, seminal vesicle, uterus, vagina, pelvic wall, abdominal wall.
        T4a - Tumor invades into prostatic stroma, uterus, 
                  vagina
        T4b - Tumor invades into pelvic wall or abdominal 
                  wall
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27
Q

What is the N-Staging and M-Staging for bladder CA (AJCC 2010)?

A

Nx - Regional lymph nodes cannot be assessed
N0 - No regional lymph node metastases
N1 - Single regional lymph node metastases in the true pelvis (hypogastric, obturator, external iliac, or presacral)
N2 - Multiple regional lymph node metastases in the true pelvis (hypogastric, obturator, external iliac, presacral)
N3 - Lymph node metastases to the common iliac

M0 - No distant mets
M1 - Distant mets

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28
Q

Why is SCC of the bladder more common in Egypt?

A

Schistosoma infection - bilharzial infections associated with SCC

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29
Q

Is the prognosis of SCC better or worse than UC?

A

Worse (except bilharzial SCC - well differentiated and low incidence of metastases)

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30
Q

How do you treat SCC of the bladder?

A

Less responsive to chemotherapy and radiation in comparison to UC. Treat localised bladder SCC with radical cystectomy, PLND, +/- urethrectomy

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31
Q

How do you classify bladder adenocarcinoma?

A
  1. Primary - arising from the bladder itself
  2. Urachal - arises from urachus
  3. Metastatic - from elsewhere
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32
Q

How do you work-up someone with adenocarcinoma found in the bladder?

A 
Need to ensure not metastatic disease:
(Possible sites of origin include: colon, stomach, lung, prostate, breast, endometrium and ovary)
Investigations:
1. CT abdo/pelvis with contrast
2. Chest imaging
3. Upper and lower GI endoscopy
4. In males PSA and DRE
5. In females: pelvic exam, CA-125, and mammogram
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33
Q

What is the prognosis of adenocarcinoma of the bladder in comparison to UC of the bladder?

A

Worse. Responds poorly to chemo or rads. No intravesical treatment options

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34
Q

How do you treat adenocarcinoma of the bladder?

A

Radical cystectomy with en bloc removal of the urachus, pelvic lymphadenectomy +/- urethrectomy. Treat metastatic adenocarcinoma based on primary.

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35
Q

What is specifically noted in the urine in urachal adenocarcinoma? What serum test may be abnormal?

A

Mucin (15-35% of the time), CEA

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36
Q

Where is localised urachal adenocarcinoma usually found in the bladder and how do you treat it?

A

Bladder dome (can be found on anterior wall as well) - treat with partial or radical cystectomy with en bloc resection of the urachus and umbilicus + PLND

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37
Q

What is the mean 5 year cancer free survival in urachal adenocarcinoma? What percentage of patients have local recurrence after excision?

A

55%, 20-50%

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38
Q

What is the confirmatory histological stain for small cell carcinoma of the bladder?

A

Stain positive for chromogranin A and synaptophysin (all other bladder cancers stain negative for this)

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39
Q

Small cell carcinoma is the most aggressive bladder cancer - what percentage of patients present metastatic?

A

50% - all patients with small cell carcinoma of the bladder should have a metastatic workup (CT abdominal/pelvis, chest imaging, Bone scan (if bony pain or elevated ALP), LFT’s)
OS < 50% @ 5 years

40
Q

How do you treat small cell carcinoma of the bladder?

A

SYSTEMIC CHEMOTHERAPY
M0: systemic etoposide and cisplatin. If patients respond consolidate therapy with radical cystectomy and or pelvic radiation
M1: systemic chemo

41
Q

What are the sites of bladder cancer metastases from most common to least?

A

Pelvic lymph nodes > liver > lung > bone

42
Q

In what percentage of patients with CIS is urinary cytology positive?

A

95%

43
Q

What kind of voiding symptoms does CIS produce?

A

Irritative LUTS

44
Q

What is the likelihood of CIS recurring and progressing following BCG?

A

Recurrence - 30% after BCG

Progression - 20% after complete response to BCG

45
Q

What are the characteristics of CIS with respect to its shape, grade and level of invasiveness?

A

Flat, high grade, and non-invasive

46
Q

What is the first line treatment for CIS?

A

BCG induction (6 cycles) 3-4 weeks after TURBT

47
Q

How and when do you check if CIS responded to BCG induction? If it is eradicated what should you do? if remains what should you do?

A
  1. Six weeks after completion of BCG - bladder biopsy and urine cytology at time of biopsy for persistence
  2. If eradicated after 1-2 induction courses of BCG maintenance BCG recommended
  3. If persistent CIS options include cystectomy or repeat BCG - if repeat induction BCG fails should consider subsequent cystectomy
48
Q

What is the surveillance schedule for eradicated CIS?

A

Cystoscopy every 3-6 months for 2 years than less often if negative. Cytology is optional. Obtain CT urogram every 1-2 years (or IVU, retrograde pyelogram)

49
Q

What are the rates for progression and recurrence for Ta lesions?

A

Progression - 5% progress to muscle invasion within 1 year of TURBT

Recurrence - 50% recur within 1 year of TURBT

50
Q

What are the EORTC criteria used for their algorithm to predict recurrence and progression in Ta and T1 lesions ?

A
  1. Number of tumors: 1, 2-7, more than 8
  2. Tumor size: less than 3cm, greater than 3cm
  3. Primary recurrence rate: less than one year, more than
    one year
  4. T category: Ta or T1
  5. CIS: Y, N
  6. Grade: high or low
51
Q

For first time TaHG lesions what should be the next step in management?

A

Re-resection TURBT - ensure correct stage and complete resection.

52
Q

When is surveillance +/- fulguration of a Ta lesion an appropriate management strategy?

A

Low Risk TaLG lesions - TaLG tumor, benign urinary cytology, and current tumor appears small, low grade and Ta.

53
Q

What are risk factors for recurrence of Ta lesions?

A
  1. Size greater than 2cm
  2. Recurrence less than 1 year from TURBT
  3. Incomplete resection
  4. Multiple tumors
54
Q

If TaLG lesion is has a high risk of recurrence how should it be managed?

A

6 weeks of intravesical chemotherapy (mitomycin, thiotepa, epirubicin) administered 3-4 weeks after TURBT. If fails (recurrence) consider BCG

55
Q

How should a TaHG lesion be managed?

A

6 weeks of BCG induction 3-4 weeks after TURBT

56
Q

How should you follow up a TaLG lesion that has been treated adequately?

A

cystoscopy at 3 months and 9 months after TURBT than yearly. If any untreated tumors than cytology should be obtained

57
Q

How should you follow up on a TaHG lesion that has been treated adequately?

A

Cystoscopy and urinary cytology every 3-6 months for two years and then less often.

58
Q

In managing Ta bladder CA when do you consider upper tract imaging with CT urogram, IVU, or retrograde pyelogram?

A
  1. Every 1-2 years if tumor is high grade

2. When there are frequent recurrences

59
Q

What are the recurrence and progression rates of T1 lesions?

A

Recurrence - 50-70% recur after treatment

Progression - 30-40% progress to muscle invasive disease after TURBT

60
Q

What is the next step in management for a first presentation of a T1 lesion?

A

Re-resection TURBT to confirm stage and complete resection

61
Q

What is first line treatment for a T1 tumor?

A

Induction (6 cycles) of BCG; 3-4 weeks after TURBT

62
Q

When would you consider an upfront partial or radical cystectomy for T1 lesions?

A

High grade, associated CIS, multifocal T1 tumor, LVI, or tumor cannot be completely excised

63
Q

What are your options if 6 weeks following BCG induction administration there is noted biopsy confirmed T1 tumor?

A
  1. Repeat induction BCG

2. Cystectomy

64
Q

How should you manage a patient that is tumor free following induction BCG?

A

Maintenance BCG

65
Q

How should you surveil a patient with T1 lesions that are treated with BCG?

A

Cystoscopy and urine cytology q3-6 months x 2 years than less frequently. CT urogram (or IVU/ Retrograde pyelogram q1-2 years)

66
Q

For patients with T2-T4 N0M0 disease what are their treatment options?

A
  1. NACT followed by radical cystectomy, urinary diversion, and pelvic lymphadenectomy (Gold standard)
  2. Radical cystectomy, PLND, and urinary diversion (if cannot tolerate NACT)
  3. Bladder preservation therapies
67
Q

How do you treat bladder cancer patients that present with T4b N1-3, M1 disease?

A

Systemic chemotherapy +/- EBRT for local control

68
Q

Is systemic chemotherapy for UC curative?

A

No

69
Q

What are first line chemotherapeutic regimens for treatment of UC?

A
  1. Gemcitibine and Cisplatin (GC)
  2. Dose dense methotrexate, vinblastine, adriamycin, cisplatin (DDMVAC)
    * similar survival between two regimens but GC less toxic*
70
Q

What is the most effective chemotherapeutic agent against UC?

A

Cisplatin

71
Q

What are types of urothelial CA with variant histologies?

A

UC can mutate into variant histology giving hybrid urothelial CA (glandular differentiation, squamous differentiation). Still treated as UC. Worst variant histology = micropapillary or nested.

72
Q

What are the principles of managing urothelial CA in a diverticulum?

A
  1. Minimise elevated risk of perforation with resection
  2. CIS can be treated with fulguration and BCG
  3. Low grade papillary can be treated with TURBT +/- intraveical therapy
  4. Recurrent or high grade tumors should be treated with a diverticulectomy or partial or radical cystectomy
73
Q

What are the principles of managing urothelial CA in the prostatic urethra?

A
  1. Non-invasive TCC can be treated with TURBT +/- TURP + BCG
  2. If tumor recurs in prostate (especially high grade or invasive) consider radical cystectomy and urethrectomy
  3. If UC invading into prostatic stroma - treatment is radical cystectomy and urethrectomy.
74
Q

What are the two types of intravesical chemotherapy?

A
  1. Chemotherapy (mitomycin, thiotepa, epirubicin)

2. Immunotherapy (BCG, interferon)

75
Q

What are the three main indications for intravesical therapy?

A
  1. Eradication of CIS with or without an associated papillary tumor
  2. Eradication of residual papillary tumor after incomplete resection.
  3. To reduce the recurrence and progression of completely resected tumors
76
Q

What is the MAJOR difference in terms of prognosis (recurrence and progression) between BCG and intravesical chemotherapy?

A

BCG decreases recurrence AND progression whereas intravesical chemotherapy only decreases recurrence.

77
Q

BCG is superior to intravesical chemotherapy for what kind of bladder lesions?

A
  1. CIS
  2. High grade tumors
  3. T1 tumors
78
Q

How long must you wait after a TURBT before giving BCG?

A

2 weeks minimum

79
Q

When can intravesical chemotherapy first be given?

A

Single dose within 24h after TURBT (ideally within 6 hours) - recommended for Ta tumors (mitomycin or epirubicin in the ABSENCE of bladder perforation because it decreases recurrence by 13%)

80
Q

What bladder tumors can be treated with intravesical chemotherapy and with what regimens?

A

Ta lesions with risk factors for recurrence.

  1. Induction: 6-9 doses once weekly 3-4 weeks after TURBT
  2. Maintenance: started right after induction 1 cycle every 1-3 months for up to one year.
81
Q

What are contraindications to giving intravesical chemotherapy?

A
  1. Gross hematuria
  2. Urinary infection
  3. Bladder perforation
  4. Traumatic catheterization
82
Q

How do you optimize the effects of intravesical mitomycin?

A

Alkalanize urine to pH>6 (mitomycin more effective at this pH)

83
Q

What is the technique for instilling intravesical chemotherapy within 6 hours after TURBT?

A
  1. CANNOT do if there is a bladder perforation
  2. Empty bladder, place catheter and install chemo into bladder and then clamp catheter.
  3. Hold in bladder for 2 hours or until patient becomes uncomfortable
  4. Can remove catheter after draining
84
Q

What investigations need to be performed before instilling intravesical chemotherapy?

A

U/A - check for gross hematuria and UTI

85
Q

What are principles of instillation of intravesical chemotherapy?

A
  1. Empty bladder prior to instillation
  2. Instillation through catheter.
  3. Attempt to hold in bladder for 2 hours.
86
Q

How does mitomycin C work?

A

Alkylating agent (inhibits DNA synthesis)

87
Q

What is the usual dose of mitomycin C?

A

40mg in 20cc sterile water administered intravesically

88
Q

What are the side effects of intravesical mitomycin C?

A
  1. Contact dermatitis

2. Irritative LUTS

89
Q

Why is systemic absorption of mitomycin rare? What can happen if it is absorbed?

A

It has a high molecular weight. Can cause myelosuppression

90
Q

What are the indications for intravesical thiotepa? (only FDA approved intravesical chemotherapeutic agent)

A

Ta, T1 and CIS bladder cancer

91
Q

How does thiotepa work?

A

alkylating agent (inhibits DNA synthesis)

92
Q

What is the dose of thiotepa?

A

60mg in 30-60cc of NS instilled weekly for 6 weeks than monthly for up to one year

93
Q

What are the possible side effects of thiotepa?

A

irritative LUTS, myelosuppression (higher than mitomycin as thiotepa has lower molecular weight) need to check complete blood count prior to every instillation.

94
Q

How does Epirubicin work?

A

Anthracycline - intercalating agent that inhibits DNA synthesis

95
Q

What is the dose of epirubicin?

A

40-100mg in 40-100cc of NS

96
Q

What are the side effects of epirubicin?

A

Irritative voiding symptoms. If absorbed systemically (low chance high molecular weight) can cause myelsuppression

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