Bladder cancer Flashcards
presentation - musc vs non musc inv, vs metastatic
75% non musc, 20% musc, 5% metastatic
cigaretter smoking dose threshold
dose dependent but 40 pk yrs is esp important. no risk plateau
4 things assd w bilateral upper tract ca
arsenic, balken nephropathy, bracken fern, aristolochia fangchi
2 polymorphisms confering higher suceptibility to environmental carcinogens
- slow acetylators, 2. glutathione s transferase M1 null
congential condition w higher risk of adnenoca
extrophy
iatrogenic condition w higher risk of adnenoca
ureterosigmoidostomy
signet cell adenoca significance
very bad
small cell/neuroendocrine markers - 3
synaptophysin, chromogranin, neuron speciic enolase
tx for small cell
VP-16 then cystectomy for ANY stage
3 premalignant lesions
- leikoplakia (20% risk of SCC), 2. cystitis glandularis (adenoca), 3. inverted papilloma (assd w TCC elsewhere)
benign lesions - 5
squamous metaplasia (50% females), nephrogenic adenoma (turbt), cystis cystica / follicularis, pseudosarcoma (spindle cell tumor), malacoplakia (rxn to chronic UTI)
significance of 9q loss
low grade tcc
significance of high p53, KI 67, matril metaloprotease
high grade
what is KI 67
marker of proliferation
tetraploidy significance
normal - found in umbrella cells
sig of low RB, e-cadgerin, p27
high grade
what is RB
“cell cycle brake” - loss promotes cancer proliferation
sig of high urokinase type pasminogen activator
high grade
nephrogenic adenoma sx
hematuria, dysuria, frequency
clinical stage for fixed vs palpable mass after turbt
fixed - T4, palpable - ct3
rate of understaging if no muscle in T1 specimen
50%
chance understaging in T1 with muscle in specimen or chance of leaving tumor behind
10-20% understaging, 30-50% residual tumor behind
retur?
all high grade T1 reduces understaging to < 10%
tumor in diverticulum - Ta vs T1
Ta - can be safely removed, T1 - may need partial cystectomy
2 situations where intraperitoneal perf can be managed conservatively
- small and late in TUR - switch to glycine, 2. large/ assd w bleeding or early in TUR - stop and retuen another time
absolute indication to e-lap in intraperitoneal bladder injury
bowel injury
LVI in T1 - prognostic sig - 3
88% chanc of understaging, increased occult LN mets, decreased survival
LVI mgmt in T1 - 2
early cystectomy with neoadjuvant chemo
risk of recurrence at 2 yrs vs 4 yrs for HG TCC
80% vs 20%
things primarily affecting recurrence - 4
prior recurrence > 1x/yr, multifocality, tumor > 3 cm, recurrence at 3 mo cysto
things affecting progression
CIS, stage (T1/CIS)
low risk bca - 3
low grade, solitary, Ta
progression risk for low risk
<5% @5 yrs
intermediate risk - 2
recurrent OR multifocal Ta/T1 low grade
progression risk for intermediate risk
10% at 5 yrs
high risk
any high grade (CIS, Ta, T1)
highest risk
multifocal T1G3+CIS
progression risk for high risk
25-50% @ 5 yrs
post TUR agents - 3
mitomicin, thiotepa, doxorubicin
when to give post TUR chemo
within 6 hrs
dwell time for post tur agents
30-60 minutes
what agent does not cause severe local tissue reaction/peritonitis with perforation
thiotepa
thiotepa risk with perf
myelosupression (lowest molecular weight)
benefit of post chemo agent
25-50% relative risk of recurrence, 15% absolute risk reduction
techniques for optimization of intravesical chemo (delayed) - 4
- relative dehydration, 2. empty bladder prior to instillation, 3. increase concentration (40 mg in 20 cc water), 4. alkalinize urine with po bicarb (reduces mitomicin degradation)
mitomycin toxicity
hypersensitivity, palmar rash, bladder contracture
thiotepa toxicity
myelpsupression- have to check weekly CBC
who is intravesical chemo best for
intermediate risk papillary, or if BCG is contraindicated
effect of intravesical chemo
recurrence only, no effect on progression
limitations of multidose chemo -3
- reduces recurrence only, 2. ineffective if prior bcg failure, 3. failure of 1 chemo agent increases failure likelyhood of another chemo agent
contraindications to BCG dose - 4
- traumatic cath, 2. recent gross hematuria, 3. unresolved UTI, 4. significant immunosupression or autoimmune disease
what are not contraindications to BCG - 4
- reflux, 2. hx treated TB, 3. positive PPD, 4. prosthetic devices
benefit to BCG
30% reduction in recurrence and progression
BCG MOA - 2
- T-helper type 1 immune response (inc IL2 and interferon gamma), 2. opposed by T helper type 2 response (increased IL-4 and IL-10)
1st steps to improve BCG tolerance
sx relieving drugs - antichol, pyridium
alternate methods of improving BCG toelrance - 3
- BCG dose reduction, 2. space tx out to 2 wks apart, 3. decrease dwell time to 30 mins
BCG sepsis meds - 2 steps
3-6 months with INH, or triple therapy (INH, ethambutol, rifampin) if severe case + steroids(!) in acute phase
supplementation with INH
B6, pyridoxine
mgmt of BCG prostatitis
anti tb meds
most common cause of BCG sepsis
traumatic catheterization
low, intermediate, high risk and chemo/BCG
low - postop chemo only, intermediate/high - postop chemo + 6 wk chemo or BCG + maintenance
indications for upfront cystectomy in nonmuscle invasive disease - 7
unfavorabel histology, LVI, bulky/incompletely resectable T1 HG, BCG failure x 2 in T1HG, prostatic stromal invasion, HGT1 in bladder diverticulum, bladder cripple with recurrent disease
unfavorable histology qualifying for upfront cystectomy
SCC, small cell, adenoca, nested or plasmacytoid, micropapillary
relative indications for RC
T1HG after repeat TUR, T1HG after BCG x 1, multifocal T1HG + CIS at presentation
upper tract studies - low risk, multifocal low risk, high risk
low risk - initial study only, multifocal low risk, every 2 yrs, high risk - q 1-2 yrs
delay in tx of small Ta with hx low/intermediate risk disesae
safe - 2 mm growth per mo
when is selective positive upper tract cytology unreliable
visible bladder tumor or bx + CIS - contamination
in female, if bladder workup negative for positive cytology
check gyn source
outcome if initial workup of positive cytology is negative
bladder source eventually in 80%
bcg failure vs chemo failure
bcg failure responds to 2nd line bcg (30-50% response) but not to chemo, chemo failure responds to bcg like untreated patient
most common cause of death in bladder ca
distant mets at the time of locoregional tx
what timeframe does progression of cancer happen after locoregional tx
within 2 yrs
small cell associated paraneoplastic syndromes - 3
ectopic ACTH, hypercalcemia, hypophosphatemia
T2a/b
Ta2 - inner muscle, b - outer muscle
T4a
t4b - prostate stroma (via SV, urethra, or bladder neck), vag, uterus, rectum. mobile. T4b - pelvic side wall, fixed
CIS of prostatic urethra or ducts and stage?
does not upstage as outcome is determined by primary bladder ca
most significant pathologic risk for progression
LN status
% upstaging from T1 at TUR to T2 at RC
40%
hydro on preop workup and cT stage
cT3
prostate prior to RC
always do prostate biopsies at 5/7 oclock. if neg, dont need to send urethral margin at RC
when to absolutely get CT chest other than abn cxr
T4, N+ on c stage
when to preserve uterus/vagina in F
better support when considering neobladder
when can a female not have orthotopic diversion
anterior vaginal wall invovlement b/c have to remove urethra
when not to preserve urethra in F and mgmt
poster based invasice ca. have to include a small strip of anterior vag for margin.
prostate/SV sparing RC
investigational as prostate is involved 40% of the time
extended LN dissection and survival
no current evicence extended LN dissection (to IMA) improves survival.
extended LN dissection and tumor involvement
involved in upto 50% of T3/4
4 situations to abort cystectomy
- LN disease unresectable, 2. extensive periureteral disease, 3. fixation to pelvic side wall, 4. invading rectum
when can you keep the urethra if there is tumor involvement
small, papillary tumors that have been resected
recurrent urethral TCC risk and diversion type
lower with orthotopic vs cutaneous diversion
how to preserve urethral innervation in female
limit dissection to above endopelvic fascia
nerve sparin cystectomy?
only if no evidence of local extension intraoperatively. 40% achieve erections. age dependent
CIS of ureter or prostate and outcome
not associated with poor outcome
noncontiguous vs contiguous involvement of prostate and outcome
contiguous = very bad, T4 disease
all of the following surgical LN characteristics impact survival: 5
LN, # LN positive, % LN positive, path stage of tumor, extranodal extension
death and women
upto 50% higher risk of death
timeframe to recurrence
most within 1st 3 yrs
who needs annual upper tract monitoring post cystectomy - 3
urethral margin, + ureteral margin, CIS
tumor location for partial cystectomy
dome of the bladder, away fro ureteral orifaces
partial cystectomy outcome
poorer outcome.
poor pronostic features in EBRT of bladder - 4
anemia, T3a> or T4, hydronephrosis, CIS (radioresistant)
benefit of neoadjuvant chemo
5% overall survival benefit
who benefits most from adjuvant
residual micromets
FGFR3 mutation and tcc type
Ta papillary
P53 chromosome location
short arm of 17
P53 pathway
DNA damage –> inc P53 –> P21 –> cell cycle arrest (G1-S)
RB gene location
chr 13q
where are mets most likely after chemo and why
cns - privelaged site
positive prognostic factors for chemo in mets - 2
LN only mets, asymptomatic
mgmt of solitary mets post chemo
resect
(absolute) criteria for neobladde - 5
live expectancy > 1 yr, manual dexterity (need for CIC), cr cl > 50 or cr < 2, normal bowel function, urethra not involved by cancer
study to do before using colon in reservoir
colonoscopy
who is not excluded from orthotopic neobladder - 3
> 80 yo, locally advanced disease, prior pelvic rsadiation
absolute contraindication for neobladder in F
ca at bladder neck or posterior bladder. must retain distal 2/3 urethra for nl urinary function
signifance of urinary retention in men post nb
likely suggests recurrence
bowel segment to use for cutaneous diversion if prior pelvic radiation
transverse colon
use fo turnbull stoma
eliminates risk of stomal stenosis
what is hematuria/dysuria syndrome
reduced HCL secretion = loss of feedback on gastrin secretion –> peptic ulcers, hematuria
cause of diarrhea after urinary diversion and mgmt
fat malabsorbtion and bile salt irritation of colon.
mgmt of persistent diarrhea after colon conduit
metamucil –> antimotility drugs –> cholestyramine
pathophys of increased renal calculi in diversion
decreased bile acids –> fat malabsorbtion and ca binding –> increased oxalate