Bladder cancer 2 Flashcards
Structures removed with radical cystectomy
men = remove bladder + prostate, followed by urinary diversion
women = typically remove bladder + uterus, followed by urinary diversion
accuracy of staging cystoscopy and TURBT for muscle invasive
Not very accurate, so patients are often upstaged after radical cystectomy
Contraindications to trimodality therapy for bladder preservation
- extensive or multifocal CIS
-tumor-related hydronephrosis - good pre-treatment bladder function
- bunch of others….
What is Stage II anatomically?
The cancer has grown into the inner (T2a) or outer (T2b) muscle layer of the bladder wall, but it has not passed completely through the muscle to reach the layer of fatty tissue that surrounds the bladder.
Stage IIIA or IIIB implies
nodal involvement
what is MVAC?
methotrexate, vinblastine, adriamycin, cisplatin
clinical behavior of the variant histologies (squamous, adeno, micropapillary, nested, plasmacytoid, sarcomatoid)
- more aggressive
T2 disease means
muscle invasive
Management of muscle invasive bladder cancer (T2 disease) generally speaking
- neoadjuvant chemo then cystectomy
Management of patient with T1a disease who has TURBT and visually resected with path showing high grade NMIBC and negative margins
- Repeat TURBT (need to ensure patient does not have component of muscle invasive disease)
Indications for BCG
Intermediate or high risk, non-muscle invasive bladder cancer:
1) cTa, high grade, intermediate risk
2) Tis, AUA high risk disease
3) cT1
management of urothelial cancer of the prostate with stroma invasion
- cystoprostatectomy +/- urethrectomy +/- neoadjuvant chemotherapy
what is cystoprostatectomy
procedure in which the bladder and prostate gland are surgically removed,
Preferred perioperative regimens for MIBC + # of cycles
MVAC with GCSF x 3-4 cycles
Gem-cis x 4 cycles
T4a means
tumor outside bladder invading into surrounding structures (prostatic stroma, uterus, vagina, seminal vesicle)
T4b means
invading pelvic wall or abdominal wall
Evidence for carboplatin-based therapy in MIBC?
- carbo has not demonstrated a survival benefit and should not be substituted for cisplatin
other RF’s for bladder cancer
- aromatic amines and aromatic hydrocarbins
- aristolochia fangchi (herb)
management of MIBC with small cell, neuroendocrine features
- neoadjuvant cis-etoposide followed by XRT or cystectomy (need to use small cell lung cancer chemo regimen – cis-etoposide)
intravesical chemotherapy options for cTa + preferred option
- gemcitabine (preferred) and mitomycin
management of superficial bladder cancers (T1 or less)
TURBT and intravesical chemo within 24 hours
Management of positive urine cytology with negative cystoscopy
- cytology of the upper tract and ureteroscopy
Stage IIIA disease means in terms of N stage
N1 disease
Stage IIIB disease is in terms of nodal staging
> N1 disease
Management of N1 disease
Neoadjuvant cisplatin based combination chemo followed by cystectomy vs. concurrent chemoRT
Management of stage IIIB disease (multiple nodes involved)
- downstaging systemic chemo or concurrent chemoRT
efficacy of gem-cis vs MVAC
- equivalent OS and PFS benefit
preferred regimens for metastatic bladder cancer
Cis-gem (toxicity profile)
DDMVAC
management of patient who isn’t a cystectomy candidate
Trimodality therapy (TMT)
chemo regimens to be given with radiation in bladder + regimen for CKD patients
Cisplatin-taxol
Cisplatin alone
IF renal dysfunction, 5-Fu/mitomycin (MMC)
what are the high risk factors for non-invasive urothelial cancers warranting treatment
- T1
- CIS or Tis
- high grade greater than 3 cm
- high grade multifocal
what is the point of a TURBT in non muscle invasive
1) Diagnostic - rule out muscle invasion (must see muscle on path)
2) debulk as much of the tumor as possible
management of patient treated with NAC with cis-gem who has cystectomy and then is found to have widely metastatic disease
- pembro
*can’t use platinum because this group has platinum-refractory disease
Checkpoint inhibitors approved for locally advanced or metastatic bladder cancer
pembro + atezo
Drug for patients with FGFR mutations
erdafitinib
management of pure squamous cell bladder cancer
cystectomy or RT
PS permitting cystectomy
0-2 (confirm)
what does Tis mean?
urothelial carcinoma in situ
Management of low-risk non-muscle invasive cancer
- surveillance after TURBT
- single perioperative dose of intravesical mitomycin C or gemcitabine at time of TURBT (CONFIRM)
Very high risk features for cT1
1) LVI
2) Prostatic urethral involvement of tumor
3) Variant histology (micropapillary
Plasmacytoid, sarcomatoid
4) T1 with extensive CIS
Management of non muscle invasive disease with very high risk features
Cystectomy
First step in management of MIBC always
neoadjuvant chemo
2 primary neoadjuvant regimens
Dose dense MVAC with GSCF OR
gem-cis
Contraindications to bladder sparing approach
hydronephrosis + <6 cm in size + no concurrent extensive or multifocal Tis + bunch of others
when is adjuvant therapy indicated for MIBC?
pT3, NOT pT2
Node positive
management of ESRD patient and cisplatin
Give 50% of the dose
Dialysis within 3 hours after giving the dose
GFR and cisplatin contraindication
- variably defined
- some will not give if GFR is less than 60
- some will still give if GFR is less than 45
- some will use split dose cisplatin
adjuvant and Neoadjuvant management of bladder adenocarcinoma
- No proven role for neoadjuvant or adjuvant therapy
Major RFs for squamous cell cancer of the bladder
- schistosomiasis in the developing world
- prolonged indwelling catheters (particularly spinal cord-injured patients)
- chronic irritants (bacterial infections, foreign bodies, chronic bladder outlet obstruction)
primary treatment of non-muscle-invasive bladder cancer
TURBT
clinical features of plasmacytoid urothelial cancer + chemo sensitivity
- aggressive
- chemo resistant
- peritoneal spread
Gene alteration that is pathognomic of plasmacytoid + pattern of disease dissemination in plasmacytoid
CDH1 gene mutation (loss of E-cadherin permits enhanced cellular migration, likely explaining unique peritoneal pattern of disease dissemination)
Management of patient who progresses on MVAC
pembro (there are several immune therapy options for patients who progress on platinum-chemo, but pembro is preferred)
*key concept. this is platinum-refractory disease
Bladder Tis management
- TURBT
- intravesical chemo within 24 hours of TURBT
Preferred FGFR inhibitor
Erdafitinib
Management of recurrent Tis that is BCG unresponsive (BCG-refractory disease)
- cystectomy
- pembro if cystectomy refused
Recurrent Tis management if ineligible for surgery or pembro
Valrubicin
Second line if no EGFR mutation
- enfortumab vedotin
enfortumab vedotin mechanism + payload
ADC targeting Nectin-4, MMAE (microtubule inhibitor)
Dosing for split dose cisplatin/gemcitabine dosing?
35/35
sacituzumab govitecan mechanism + payload
ADC that targets Trop-2, a transmembrane glycoprotein highly expressed in most urothelial carcinomas, and is coupled with SN-38, an active metabolite of irinotecan.
Toxicity profile of Tivozinib (tivo)
best tolerance of TKI (approved for frontline in Europe) + has issues with tolerance
What are the drugable FGFR mutations?
2/3, 1 & 3 are also druggable
Primary EV contraindication to know
Uncontrolled DM2 (hyperglycemia)
Erdafitinib indication (based on molecular profiling)
FGFR3 or FGFR2/3 fusion
Management of muscle invasive small cell bladder cancer
Neoadjuvant cisplatin + etoposide followed by consolidation surgery or radiation for local control
Surgery for UTUC
NephroU
Adjuvant therapy for UTUC
4 cycles of gemcitabine/platinum
What is the continuum of risk in NMIBC?
Non–muscle invasive bladder cancers exist on a continuum of risk in patients, with T1 high-grade (T1Hg) bladder cancer at the aggressive end of the spectrum.
Ocular AE’s of erdafitinib
- dry eyes
- retinal pigment epithelium detachment
- central serous retinopathy, conjunctivitis
- increased lacrimation
EV side effects
fatigue, peripheral neuropathy (nerve damage resulting in tingling or numbness), decreased appetite, rash, alopecia (hair loss), nausea, altered taste, diarrhea, dry eye, pruritus (itching) and dry skin
EV payload
MMAE (monomethyl auristatin E), microtubule inhibitor
New gene therapy approved for NMIBC + mechanism
Nadofaragene firadenovec (adenovirus that delivers INF alfa cDNA into bladder epithelium)
Classification of NMIBC
Ta
Tis (or CIS)
T1
management of high risk NMIBC
Restaging TURBT in 4-6 weeks. If no indication for cystectomy, you give intravesical BCG
Intravesical BCG induction and maintenance
- Induction
- 3 years maintenance
- followed by surveillance.
What is split dose cisplatin? Dose reduction? Original dose?
50% dose reduciton, 35 mg/m2
Galsky criteria for cisplatin ineligibility
WHO or Eastern Cooperative Oncology Group performance status ≥2, or Karnofsky performance status 60–70%
Common Terminology Criteria for Adverse Events version 4 grade ≥2 peripheral neuropathy
Grade ≥2 audiometric hearing loss
New York Heart Association class III heart failure