HYU Onc - Bladder and Upper Tract Flashcards
Microhematuria definition
> or = 3 RBCs/hpf on microscopic evaluation of a single, properly collected urine specimen
Evaluation should not change based on presence or absence of AC/anti-plt meds
Microhematuria: Low-Risk
Must meet ALL of the following criteria:
Women < 50yo
Men < 40yo
<10 pack-years
3-10 RBCs/hpf
No prior episodes of MF
No other risk factors
Microhematuria: Intermediate Risk
If you meet ANY of the following criteria:
Women 50-59 yo
Men 40-59 yo
11-30 pack years
11-25 RBCs/ hpf
Presence of additional risk factors
Previously low-risk without prior evaluation and 3-25 RBCs/hpf
Microhematuria: Intermediate Risk
If you meet ANY of the following criteria:
Women 50-59 yo
Men 40-59 yo
11-30 pack years
11-25 RBCs/ hpf
Presence of additional risk factors
Microhematuria: High Risk
If you meet ANY of the following criteria:
Man or woman >60yo
>30 pack years
>25 RBCs/hpf
History of gross hematuria
Previously low-risk without prior evaluation and >25 RBCs/hpf
Management of low-risk microhematuria
Shared decision making
Can repeat UA within 6 months or
Cysto + US
Management of intermediate-risk microhematuria
Cysto + RUS
Management of high-risk microhematuria/gross hematuria
Cysto (for all)
CTU > MRU > retrograde pyelograms and noncon axial imaging or RUS
Additional risk factors for urothelial carcinoma
Irritative LUT voiding symptoms
History of cyclophosphamide of ifosfamide chemotherapy
Family history of US or lynch syndrome
Occupational exposure to benzene chemicals or aromatic amines
History of chronic indwelling foreign body in the urinary tract
Imaging when microhematuria in a patient with family history of RCC or known genetic renal tumor syndrome
Perform upper tract imaging regardless of risk stratification
When use urine cytology and markers in MH patients?
Do not use in initial MH evaluation
Can use cytology for patients with persistent MH + irritative LUTS or RFs for CIS after a negative initial MH workup
MH follow-up after negative evaluation
Repeat UA in 12 months
If UA negative, discontinue further evaluation
If UA persistent MH, shared decision making regarding need for initial evaluation
After negative evaluation, initiate further evaluation if new gross hematuria, increasing degree of MH, or new urologic symptoms
Bladder Cancer Staging
Tis = mucosa
T1 = lamina propria
T2 = Muscularis propria
- a = inner
- b = outer
T3 = Perivesical tissue/fat
- a = microscopic
- b = macroscopic
T4 = Extravesical
- a = adjacent organs
- b = body wall
Ta: This refers to noninvasive papillary carcinoma. This type of growth often is found on a small section of tissue that easily can be removed with TURBT.
Low risk bladder cancer
LG solitary Ta less than or = to 3 cm
PUMLUMP
Intermediate Risk Bladder Cancer
Recurrence of LG Ta within 1 year
Solitary LG Ta >3cm
Multifocal LG Ta
HG Ta < or = to 3 cm
Any LG T1
High Risk Bladder Cancer
HG T1
Any Recurrent HG Ta
HG Ta > 3 cm or multifocal
Any CIS
Any BCG failure in HG patient
Any variant histology (micropapillary, sarcomatoid, plasmacytoid)
Any LVI
Any HG prostatic urethral involvement
Positive cytology with normal cysto in a patient with a history of NMIBC
Consider upper tract imaging, prostatic urethral biopsies, blue light cysto, ureteroscopy, random bladder biopsies
Variant histology, extensive squamous or glandular differentiation, + LVI
Obtain GU pathologist review
Offer restaging TURBT 4-6 weeks after diagnostic TURBT (if attempting to spare bladder)
Or, offer up front radical cystectomy
When is the use of urine markers appropriate?
For NMIBC, can use biomarkers to assess response to BCG and to adjudicate equivocal cytology
- Should NOT use in lieu of cytology
- Should NOT use for surveillance of low risk patients with with normal cytology
- SHOULD use cytology with surveillance cystoscopy for IR and HR disease
When do you perform a restaging TURBT?
Within 6 weeks of initial TURBT
If incomplete resection
If pathology is high-risk HG Ta OR HG T1
Must get muscle in specimen
Single dose intravesical MMC or gemcitabine use?
Postop
Consider in suspected/known LG disease within 24 hours of TURBT, except in cases of suspected perforation or extensive resection
When do you use BCG?
Don’t use in LR
Consider in IR
Use in HR
If it works, maintenance BCG (3 weekly doses starting 3 months after induction) for 1 year in IR and 3 years in HR
What is maintenance BCG dosing/timing?
If it works, maintenance BCG (3 weekly doses starting 3 months after induction) for 1 year in IR and 3 years in HR
What do you do for persistent/recurrent NMIBC s/p 1 induction course of BCG?
- Ta?
- CIS?
- HG T1?
Ta - Second induction course of BCG
CIS - Second induction course of BCG
RC w/o NAC also an option for both of these
HG T1 - RC
Persistent/recurrent HG or CIS within 6 months of 2 induction courses BCG or induction + maintenance BCG?
No more BCG
Unwilling or unfit for RC after 2 courses of BCG with recurrence within 12 months –> clinical trial vs other intravesical therapy (valrubicin, gemcitabine, docetaxel), vs. systemic pembro for CIS
Cystoscopy follow-up for bladder cancer patients
After initial evaluation/treatment, first surveillance cysto should be within 3-4 months
If this is negative, the frequency of subsequent surveillance cysto (w/ cytology if IR/HR) varies based on risk stratification
Low-risk NMIBC surveillance cysto schedule
After initial evaluation/treatment, first surveillance cysto should be within 3-4 months
Next cysto 6-9 months later
Then yearly
Shared decision making after 5 years
*In-office fulguration is an option for LG Ta disease with <1cm papillary recurrence
Intermediate-risk NMIBC surveillance cysto schedule
After initial evaluation/treatment, first surveillance cysto should be within 3-4 months
Cysto/cytology q3-6 months x2 years
q6-12 months x2 years
Then yearly
Consider surveillance upper tract imaging every 1-2 years
High-risk NMIBC surveillance cysto schedule
After initial evaluation/treatment, first surveillance cysto should be within 3-4 months
Cysto/cytology q3-4 months x2 years
q6 months x2 years
Then yearly
Consider surveillance upper tract imaging every 1-2 years
Treatment for BCG sepsis
- MOA for the drugs?
Corticosteroids + NSAIDs + Isoniazid 300mg + Rifampin 600mg + Ethambutol 1200mg daily
Isoniazid inhibits mycobacterial cell wall formation
Rifampin inhibits RNA polymerase
Ethambutol inhibits mycobacterial cell wall formation
Pyridoxine (B6) is administered with Isoniazid to prevent peripheral neuropathy
Persistent fever without sepsis or UTI following BCG
Isoniazid x 3 months
Timing of BCG and TURBT
Don’t give BCG until >1 week after TURBT due to risk of BCG sepsis
Can you give BCG in immunocompromised patients?
BCG is safe in immunocompromised patients
- Including patients with autoimmune disease, transplant patients, and patients undergoing systemic chemotherapy
BCG is dependent on an intact immune system, so use MMC (DNA x-linker) for intravesical therapy in patients on immunosuppression (chronic steroids for RA or anti-TNFa for Crohn’s)
Urothelial CIS of the prostatic urethra during TURP?
Repeat BCG Tx to reduce recurrence of CIS
Positive cytology and negative cysto?
Prostatic urethral biopsies should include at 5 and 7 o’clock positions, where the ejaculatory ducts insert
These are most common sites of occult disease
Granulomatous prostatitis
Common following iBCG
No intervention needed
mBCG can continue
Valrubicin uses
Valrubicin is FDA approved for BCG-refractory CIS and HR disease in a non-cystectomy candidate
Recurrent tiny (<1cm) low grade Ta after BCG
fulgurate and observe
Persistent CIS after induction in a high risk patient
Repeat induction BCG
Best method for detecting recurrent CIS after induction BCG
blue-light cysto
Hexaminolevulinate
BCG-unresponsive
Persistent/recurrent NMIBC must undergo iBCG + at least one mBCG to be ‘BCG-unresponsive’
Anktiva
IL-15 superantagonist - used with BCG in BCG- unresponsive CIS +/- Ta/T1
Side effects of MMC
9% rash (contact dermatitis)
6-41% chemical cystitis
How to optimize MMC effectiveness
Void/CIC prior
Dehydration to prevent dilution
Alkalinization with Na-bicarb
Increase drug concentration (want 40mg/20mL)
Not helpful: abx, NSAIDs, antimuscarinics
T1 tumors with aggressive features
(>3 cm, micropapillary/variant histology, concomitant CIS, LVI)
Up front cystectomy without NAC
When do you treat asymptomatic ileal conduit urine cultures?
Asymptomatic IC cultures are >75% positive
Only need to be treated if culture grows proteus or pseudomonas due to risk of stone formation
Risk of LN metastasis at time of RC performed for recurrent T1 or CIS
10-15%
Nephroureterectomy in a patient with one kidney and prior RC/IC
Leave IC in place for use with future renal transplant
Persistent disease (any) on mid-cycle TURBT during chemoradiation
Proceed to RC
Urine Assay: UroVysion FISH
Detects aneuploidy from chromosome 3, 7 and 17 and homozygous loss of chromosome 9p21
Can adjudicate equivocal urine cytology
Urine Assay: ImmunoCyt
Immunohistochemistry for urothelial antigens
Can adjudicate equivocal cytology
Urine Assay: BladderCheck
Enzyme innunoassay for NMP22
Used with cytology for Dx and surveillance
Urine Assay: BTA
Enzyme immunoassay for bladder tumor antigen
Nephrogenic Adenoma
- What is it?
- Sxs?
- Tx?
Rare benign metaplastic response to urothelium injury
Hematuria and irritative voiding sxs
Cystoscopy looks like low-grade papillary tumor
TUR + > or = 1 years of antibiotic suppression
Inverted papilloma of the ureter
Can behave malignantly, so survey bladder and upper tracts
Conservative management with surveillance for at least two years is recommended
Instillation of periop chemo after complete TURBT only works if given within how long?
24 hours after surgery
5mm filling defect in distal ureter + biopsy shows LG UC
Ureteroscopic tumor ablation
Risk of upper tract UC in patient with bladder Ca diagnosis?
10%
Risk of bladder cancer in patients with UTUC diagnosis?
~40%
How to follow cystitis glandularis?
Could have risk of transformation to adenocarcinoma
Survey with cysto or UA
Lit: SWOG 8216
1991
Intravesical BCG > Doxorubicin for preventing NMIBC recurrence
RCT
BCG = immune system activator
Doxorubicin = DNA intercalator
Lit: BCG Complications
1992
Intravesical BCG is generally well tolerated but can lead to serious adverse effects
2.9% fever
0.9% granulomatous prostatitis
0.7% PNA/hepatitis
0.5% arthralgias
1% hematuria
0.3% rash
0.3% ureteral obstruction
0.4% epididymitis
0.2% contracted bladder
0.1% renal abscess
0.4% sepsis
0.1% cytopenia