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Medical oncology > Bladder CA > Flashcards

Bladder CA Flashcards

1
Q

What is the most common presenting symptom in bladder cancer?

A

Painless haematuria

Seen in >80% of patients

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2
Q

What is the most common histology of bladder carcinomas?

A

Transitional cell carcinomas

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3
Q

Besides transitional cell carcinomas, what are the other histologies?

A 
Lymphoepithelioma-like
Sarcomatoid carcinomas
Micro papillary or nested variants
Primary squamous cell carcinomas
Adeno carcinomas
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4
Q

What is the standard treatment of muscle-invasive bladder cancer?

A

Radical cystectomy with extended lymphadenectomy

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5
Q

What supports the use of CDDP-based neoadjuvant chemotherapy for bladder cancer?

A

Advanced Bladder Cancer Meta-analysis collaboration published in Eur Urology in 2005

A meta-analysis of 11 RCTs with 3000 patients

5% absolute increase in 5-year OS
9% absolute increase in 5-year DFS

This is compared with Radical cystectomy alone

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6
Q

What is the evidence for adjuvant chemotherapy for bladder cancer?

A

Leow et al. 2013 updated meta-analysis in Eur Urol 2014

Updated meta-analysis of 9 RCTs including 950 patients for usage of CDDP-based adjuvant chemotherapy

OS benefit with HR 0.8 and DFS benefit with HR 0.65
- DFS benefit more apparent in those with Positive lymph node involvement.

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7
Q

What are the clinical indicators that determine if a patient is suitable for bladder preservation?

A

Early tumor stage

- including high-risk T1 disease, T2

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8
Q

What are the 5 bladder tumor marker tests?

A 
BTA-Stat
BTA-TRAK
NMP-22
uCyt+
UroVysion

Non shown to be superior to Urine cytology and cystoscopy

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9
Q

What are the risk factors for Bladder CA?

A

1) Age
2) Toxins
- Smoking
- Aniline-containing dyes, arsenic
- Phenacetin
- Arsenic
3) Chronic inflammation
- Chronic cystitis/UTI
- Schistosomiasis (S.Haematobium –> SCC)
4) Cytotoxic agents
- Pelvic RT
- Cyclophosphamde

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10
Q

Tell me about the bladder cancer staging for T.

A

Ta = Non-invasive papillary carcinoma

T1 = Tumor invades sub epithelial connective tissue

T2 = invades muscle

  • T2a=invades superficial muscle (inner half)
  • T2b=invades deep muscle (outer half)

T3 = invades perivesical tissue

  • T3a=microscopically
  • T3b=Macroscopically with extravehicular mass

T4=Tumor invades any of the following: prostate, vagina, pelvic wall/abdominal wall

  • T4a=invades prostate, uterus, vaginalis
  • T4b=invades pelvic wall/abdominal wall
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11
Q

Tell me about the N staging for bladder cancer

A

Regional LN are those within true pelvis.
All others are distant lymph nodes

N1 = mets in a single LN, 2cm or less

N2 = Single lymph node, >2cm, but 5cm or smaller; OR
- multiple LN, but none >5cm

N3 = Mets in a LN >5cm

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12
Q

How does completeness of TURBT relate to OS?

A

Completeness of TURBT is a strong prognostic factor for OS for both superficial and muscle-invasive disease

R0 = 10y OS 50%
R1 = 10y OS 30%
R2 = 10y OS 20%
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13
Q

What are the characteristics that are a/w higher chance of recurrence?

A

High Grade
Diffuse Tis alone or in a/w papillary tumors
>3 bladder lesions (any >3-5cm)
Vascular invasion
T1b - invasion of the deep portion of the lamina propria
Multiple recurrences within a short period of time (eg >2 in a year)
Incomplete resection due to diffuse bladder involvement or unfavorable location
Presence of tumor within 3-6 months after initial TUR

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14
Q

What is considered intermediate and high risk disease?

A

Multifocal Tis
G3 Ta or T1 with Tis
Rapidly recurring after TURBT

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15
Q

When do you treat with prophylactic intravesical chemotherapy ?

A

Immediately after TURBT (within 24 hours) for ALL superficial bladder cancer

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16
Q

What is the usual treatment for prophylactic intravesical chemo?

A

Usually Mitomycin-C

40mg in 40 Mls

Evidence comes from meta-analysis of 1500 patients of 7 RCTs over 3.5 years
- Sylvester 2004 in J Urol

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17
Q

What is the additional therapy for intermediate and high risk disease?

A

BCG most commonly used
Alternatives: Mitomycin C, or Epirubicin

Induction course of BCG once every week for 6 weeks–>
Intermittent maintenance cycles of e-week courses repeated Q3-6monthly –>
Q6-monthly up to 3 years
- This provides a 20% absolute reduction in recurrence rate
- Saint et al 2001 Urology

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18
Q

What are the agents used in intravesical treatment?

A

1) Intravesical BCG
2) Intravesical Chemotherapy
- Thiotepa
- Mitomycin-C
- Epirubicin/Doxorubicin

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19
Q

How would you monitor a patient after TURBT?

A

1) Cystoscopy
2) Urinary Cytology
3) Image upper urinary tract every 12-24 months as there is a 5% lifetime risk for development of upper tract tumor after Dx of bladder cancer

Cystoscopy/cytology:

  • every 3 months for 2 years
  • 6-monthly for 2 years
  • yearly indefinitely
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20
Q

What are the side-effects of BCG?

A 
Frequency (70%)
Cystitis (70%)
Fever (25%)
Haematuria (25%)
BCG-osis = BCG-sepsis (very rare, but can be fatal)
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21
Q

What is the role of maintenance BCG?

A

Lamm et al.

Many experienced Significant G3 toxicity
Only 16% completed treatment
3-week courses every 3-6 months, then every 6 months for up to 3 years

Provides a 20% absolute reduction in recurrence rate

22
Q

What is the side-effect of intravesical thiotepa ?

A

Significant systemic absorption and toxicities of myelosuppression
Irritating voiding symptoms

23
Q

What are the general complications of intravesical treatment?

A

Dysuria
Frequency
Urgency
Bladder fibrosis and contracture

24
Q

What are the treatment modalities for muscle-invasive disease?

A

1) Surgery
2) Neo-adjuvant chemotherapy
3) Adjuvant chemotherapy
4) Bladder-Sparing approaches

25
Q

What does radical Cystectomy entail removal of?

A

1) Bladder
2) Prostate
3) Seminal vesicles
4) Proximal urethra
5) Fallopian tubes
6) Ovaries
7) Anterior vaginal wall
8) Bilateral pelvic LN dissection

  • Recent data shows that removal of prostate may be spared when there is no direct extension of tumor to urethra, prostatic duct or stroma
  • Improved potency ad urinary incontinence
26
Q

What are the methods of urinary diversion that you know of?

A

1) Ileal conduit
2) Continent Cutaneous diversion
- Pouch made of aperistaltic bowel segment
- requires CIC
- no stoma
3) Orthotopic neo bladder

27
Q

What is the minimum number of LN tt should be removed?

A

10

From retrospective data from INT 0080, those with >10 LN removed had significantly better outcome

28
Q

When is chemo radiotherapy an option for bladder preservation?

A

More effective in:
Solitary T2 or early T3
Tumors

29
Q

How is chemo radiotherapy done?

A

CDDP or Carboplatin
- CDDP 40 mg/m2 or Carboplatin AUC2. Weekly for 6/52

Alternative radiosensitizers:

  • Capecitabine
  • Paclitaxel
  • Gemcitabine

Outcome of local control dependent on goal RT dose. ~60-70Gy

Requires repeat TURBT with multiple biopsies 6weeks after chemo radiotherapy.

30
Q

When is neoadjuvant chemotherapy considered?

A

Operable T2-4a muscle-invasive disease

This came about because failure rate of 30-45% after surgery

31
Q

What are the advantages and disadvantages of neoadjuvant chemotherapy?

A

Advantages:

  • delivered early when burden of micromet expected to be low
  • Allows evaluation of response (Chemosensitivity of tumor tested)
  • Tolerability of chemo likely to be better before surgery

Disadvantages:

  • delay cystectomy
  • S/e of chemo may affect outcome of surgery
  • error in staging may lead to over treatment
32
Q

What is the evidence for neoadjuvant treatment?

A

1) MRC/EORTC Lancet 1999

N=1000 for curative surgery or radical RT
2 arms:
1) neoadjuvant chemo with CMV
2) No neoadjuvant.

Neoadjuvant chemo

  • Cisplatin, methotrexate, Vinblastine
  • q21days X 3 cycles

Results:
pT0 after CMV = 32% in cystectomy group (55% of all patients)
Initially no survival improvement seen, but data reached significance are 8y f/u showing 15% reduction in risk of death with neoadjuvant chemo.

But difficult to compare outcomes as groups are unbalanced. Those who got RT tended to have poorer PS, earlier T and N stage and were older. 
========
2) Grossman NEJM 2003 
Planned for radical cystectomy. N=300 
2 arms:
1) Radical cystectomy alone
2) 3# of MVAC --> Radical cystectomy

Chemo Cycle Q28days

RESULTS:

  • med OS 45m vs 75m (neoadjuvant)
  • 5y OS 55% vs 40%
  • improvement in survival a/w absence of residual cancer in cystectomy specimen.
  • pCR Rae 40% vs 15% (no chemo)
33
Q

Under what circumstances may TURBT alone be curative?

A

Solitary lesion

34
Q

Describe the Tri-modality approach of TURBT+ChemoRT

A

As part of bladder preservation, uses TURBT, Chemotherapy and RT

1) TURBT
- as complete as possible
2) ‘adjuvant’ CRT with either approach:
- Concurrent CRT
- Induction chemo –> Concurrent ChemoRT
3) Restaging TURBT
4) 2 scenarios:
- Consolidative Therapy in responding patients
- Cystectomy in non-responders if residual tumor still present

35
Q

What is the outcome of Tri-modality treatment ?

A

Typical 5-yr survival is 50%

- 80% of whom has an intact bladde

36
Q

Any role for CDDP-free RT sensitization?

A

Yes BC 2001
NEJM 2012

N=360
>80% T2 tumors
All N0

2 arms:

1) ChemoRT
2) RT alone

Chemo:

  • 5FU 500/day X 5 days Week 1 and 4
  • MMC 12 D1

Results:
No OS difference, likely due to salvage Sx in RT alone patients.
PEP met: 2y LR DFS 60% vs 50%
5y OS 50% vs 35% (trend)

37
Q

What are the poor prognostic factors in metastatic bladder cancer in second line setting?

A

PS >0

Hb

38
Q

What are the CDDP-containing chemo options?

A

1) MVAC
2) Gem-CDDP
- or Gem-Carbo

39
Q

What is the expected RR with MVAC

A

About 70% with CR 50%
But very toxic
Sternberg J Urol 1985

Not as tolerable as cf CDDP/Gem

Other series show MVAC>CDDP
RR about 40% vs 10% with OS 12.5m vs 8m

40
Q

Between HDMVAC and MVAC. Which is better?

A

HDMVAC >MVAC in terms of increased RR by 1.5x.

But OS seems equivalent.

41
Q

Any rose for ddMVAC as opposed to MVAC?

A

Yes. Borderline statistically significant relative reduction in risk of PD and death

EORTC 30924 by Sternberg Eur J Cancer
- updated 2006

Differences show up in 7y update.

N=260
Met
Unresectable T3-4
Chemo-naive

RESULTS:
CR 20% vs 10%
PR ~40% 
5y OS 22% vs 13.5% (MVAC)
Med Survival 15.1m vs 14.9m (MVAC) 
7y med PFS 9.5m vs 8m
42
Q

Gem/CDDP vs MVAC. What is the result?

A

GC=MVAC
Von dear Maase JCO 2000

T4b
N2-3
Muscle invasive
No prior chemo 
N=400
2 arms:
1) Gem/CDDP
- Gem (1000 D1,8,15) Q28d
- CDDP (70) D2 Q28d
2) MVAC
- MTX (30) D1, 15, 22
- Vinblastine (3) D2, 15, 22
- Doxorubicin (30) D2
- CDDP (70) D2
Q28days

RESULTS:

  • no substantial difference in Overall RR ~45%
  • no difference in OS 15m (MVAC) vs GC 14m (trend)
  • 5y OS 13% vs 15% (MVAC) (trend)
  • med PFS 7.7m vs 8.3m (MVAC)
  • no diff in TTP/Tx failure either
  • Gem/CDDP has fewer side effects than MVAC
43
Q

Any value in addition of Paclitaxel to met Bladder CA chemo?

A

ORR improved 55% vs 45%
MOS no different 15m vs 12m (trend)
FN rate 13% vs 4%

Bellmunt JCO 2012 
2 arms:
1) Gem (1000) D1,8,15, CDDP (70) D2 
- Q28days
2) Pac (80) D1,8
CDDP (70) D1
Gem (1000) D1,8 
- Q21.
44
Q

How about ddMVAC and ddGC?

A

Bamias JCO 2011

Outcomes almost the same. 
ddGC = better tolerated
- Gemcitabine 2500
- CDDP 70
- Q14d

RESULTS:
ORR 47% (ddMVAC) vs 47% (ddGC)
OS 18.5m vs 21m (ddGC)

45
Q

Is Carbo = CDDP in Bladder CA?

A

No
Data suggests CDDP > Carbo in terms of efficacy
- MA Galsky Annals 2011 CDDP>Carbo in terms of CR, ORR

46
Q

What is the definition of those unfit for CDDP?

A

ECOG 2

CCT

47
Q

What are possible 2nd line chemotherapy?

A

No standard

1) Taxanes
2) Pemetrexed
3) ?Eribulin
4) Vinflunine

RR 10-20%

48
Q

Tell me the evidence for Vinflunine

A

Bellmunt JCO 2009
Phase 3 study with 370 patients

Vinflunine > BSC
320mg/m2 Q21days

RR 10% vs 0%
PFS 3m vs 1.5m
Med OS 7m vs 4m
Significant hematological toxicities

Vinflunine is a vinca alkaloid, inhibits micro tubules

49
Q

How about the evidence for Gem-Pac as 2nd line

A

Albers in Ann Onco 2011

N=100

6# Gem/Pac > vs Gem/Pac until PD

ORR 40% with PFS 3.5m and OS 8m

50
Q

Why in first line do we elect to use Gem/CDDP?

A

MVAC >CDDP
MVAC = ddMVAC
MVAC = GC (Von der Masse JCO 2000)
PGC = GC

Medical oncology (53 decks)

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