Campbell Management Strategies for NMIBC Flashcards
Low-grade Ta lesions recurrence rate ____ and progression rate ____.
Ta Recurrence rate 50-70% and Progression rate less than 5% of cases
High-grade T1 lesions recurrence rate ____ and progression rate ____ .
High-grade T1 recurrence rate 80%
Progression rate 50% in 3 years
Prognosis correlates with: (5)
Tumor size Multiplicity Papillary vs sessile configuration Presence or absence of LVI Status of remaining epithelium
High grade and low grade CAs may essentially be considered ___.
Different diseases
Chromosomal alterations –> oxidative DNA damage –> 2 separate genetic pathways in UC development
____ tumors could almost be considered benign in contrast to ___ tumors.
Papillary Ta tumors = almost considered benign compared to high-grade tumors.
____ of Ta tumors are high grade.
Most important risk factor for progression is ___, NOT ____
2.9% to 18% are high grade.
Most important risk factor for progression is GRADE, NOT stage.
CIS is regarded as a precursor to the development of ____.
Invasive high-grade cancer
Lesions interpreted as ____ are regarded as being the same entity as CIS.
Severe/high-grade dysplasia
____ % of patients with CIS develop muscle invasion if untreated, especially if associated with papillary tumors.
40-83% of CIS develop MIBC, esp. if associated with papillary tumors.
T1 tumors = usually papillary with a narrow stalk.
A ___ appearance suggests deeper invasion.
Nodular or sessile appearance
Deep penetration into the ____ increases the risk of ___ and ___.
Lamina propria, muscularis mucosae
Increases risk of recurrence and progression
These also increase risk of progression and recurrence in T1 tumors: (3)
LVI
Pyuria
Bladder neck involvement
____ often indicated muscle invasion.
Hydronephrosis
CT urography is commonly performed BEFORE TUR to: (2)
Identify other sources of hematuria
Assess extravesical urothelium (field change nature of UC)
Resection is performed using ____ irrigation and resectoscope, with bladder filled _____.
This minimizes: (3)
Continuous flow
Only enough to visualize bladder contents
(3)
Bladder wall movement
Lessens thinning of detrusor due to overdistention
Reduces risk of perforation
____ tumors can be removed without the use of electrical energy.
___ lessens the chance of perforation.
Friable, low-grade tumors
Lifting the tumor edge away from detrusor
** minimizes chances of bladder perforation and unnecessary cautery damage
After visible tumor is resected, an additional pass of the cutting loop or cold-cup biopsy can be obtained to ____.
…determine the presence of muscle invasion.
Non-muscle invasive bladder CA is the term for malignant urothelial tumors that ___.
… have NOT invaded the detrusor muscle of the bladder.
** Encompasses the relatively benign course of low-grade papillary tumors, the more aggressive clinical course of high-grade tumors including urothelial carcinoma in situ (CIS), and high-grade Ta and T1 tumors
Approximately ____ of bladder tumors are non–muscle invasive at presentation with:
____ as stage Ta
____ as T1, and approximately
____ as CIS
Approximately 70% to 80% of bladder tumors are non–muscle invasive at presentation with 60% to 70% as stage Ta, 20% to 30% as T1, and approximately 10% as CIS
____ is the most common presenting symptom of NMIBC.
The presence of ____ in the absence of ____ is also associated with CIS with some studies reporting rates of up to ___ %.
Painless hematuria (either visible or non-visible).
** Patients with visible hematuria have reported rates of bladder cancer much higher than that observed in patients with non-visible (>3 RBC/hpf on microscopic urinalysis) hematuria.
The presence of irritative voiding symptoms in the absence of UTI; up to 80%
____ and ____ are indicated in patients with hematuria and/or unexplained irritative symptoms.
Cystoscopy and upper tract imaging are indicated in patients with hematuria and/or unexplained irritative symptoms.
** In a review of 600 patients diagnosed with interstitial cystitis, 1% of the patients had a missed diagnosis of urothelial carcinoma, although the majority of these patients did not have hematuria.
Resection of diverticular tumors presents significant risk for ___.
Accurate staging is difficult because of ____.
Therefore: low grade diverticular tumors are best treated with ____ + ____ , followed by ____ if high-grade.
Bladder wall perforation
The absence of underlying detrusor.
**Invasion beyond the diverticular lamina propria immediately involves perivesical fat (stage T3a by definition)
Combined resection + fulguration of the base
Followed by repeat resection if high-grade
** High-grade requires adequeate sampling of tumor base despite near certainty of perforation –> leave IFC for several days to allow for urothelial healing.
Partial or radical cystectomy should be strongly considered for high-grade diverticular lesions because _____.
…tumors can penetrate extravesically with relative ease given the lack of a muscularis layer in the diverticula
Tumor near the ureteral orifice:
____ causes minimal scarring and may be safely performed, including resection of the orifice if necessary.
Pure cutting current
*** Resection of the intramural ureter may lead to complete eradication of some tumors but risks reflux of malignant cells. The clinical implications of this are unclear
** As long as resection of the ureteral orifice is performed with pure cutting current, scarring is minimal and obstruction unlikely.
____ resection of bladder tumors represents another alternative, relatively novel resection technique that can be performed with the traditional loop electrode, Hybrid-Knife, holmium laser, Thulium laser, or KTP lase.
En bloc
***This technique involves excision of the entire tumor with underlying segment of muscle with the specimen being resected and extracted intact, rather than piecemeal. The benefit of this derives from less cautery artifact, thereby allowing more accurate assessment of muscle invasion by pathology.
If a tumor appears to be muscle invasive, may be performed in lieu of complete resection, given the likelihood of subsequent cystectomy.
Biopsies of the borders and base to establish invasion
TURBT: Perforations tend to occur in ___ with ___, particularly in cases involving previous treatment with multiple courses of intravesical therapy
Perforations tend to occur in elderly patients with large posterior wall tumors, particularly in cases involving previous treatment with multiple courses of intravesical therapy.
The incidence of perforation can be reduced by attention to technical details (3):
- Avoiding overdistention of the bladder
- Anesthetic paralysis during the resection of significant lateral wall lesions to lessen an obturator reflex response
- Large, bulky tumors and those that appear to be muscle invasive are often best resected in a staged manner
TURBT: Majority of perforations are ____, but ____ is possible when tumors are resected at the dome.
Majority = extraperitoneal Dome = intraperitoneal
- The risk of tumor seeding from perforation appears to be low
- ** Bladder perforation during TUR does appears to be associated with greater risk of recurrence and worse disease-free survival in a series published by Comploj et al. (2014)
TURBT: Extraperitoneal bladder perforation during TURBT can typically be managed ____. Intraperitoneal perforation is less likely to close spontaneously and usually requires ____.
Extraperitoneal = prolonged urethral catheter drainage.
Intraperitoneal = open or laparoscopic surgical repair.
In the setting of high-grade T1 tumors, ____ is recommended within ____ of initial TURBT based on the well- established risk of identifying worse prognostic findings or upstaging to muscle-invasive disease in up to ____% of repeat TURBT specimens.
Repeat TURBT
6 weeks
25-30% of repeat TURBT specimens
- This is especially important if no muscle is identified on initial pathology, where repeat resection of patients with T1 disease can identify upstaging to muscle-invasive disease in up to 49% of cases
The efficacy of BCG in preventing recurrence and progression appears to be higher in patients with high-grade papillary tumors and CIS if ____.
a restaging TURBT was performed before instillation of BCG.
If residual stage T1 is noted on repeat TURBT, risk of progression has been demonstrated to be as high as ___, thereby suggesting potential benefit of ____ in these patients.
80%
Early cystectomy
AUA guidelines recommend ____, within ____ of the initial TURBT in patients with incomplete initial resection, and patients with stage T1 disease. These guidelines also recommend consideration of repeat TURBT in patients with high-risk, high- grade Ta tumors
repeat TURBT of primary tumor site, to include muscularis propria
6 weeks
The current consensus is that random biopsies are not indicated in _____, but there remains no consensus with regard to patients with high-grade disease, and many urologists perform random biopsies in this setting particularly if urine cytology is positive.
in low-risk patients (i.e., those with low-grade papillary tumors and negative cytology)
Can you perform TURP and TURBT at the same setting?
YES, if bladder tumor is low-grade. Traditional teaching is that TURP and TURBT of a low-grade bladder tumor may be performed at the same setting but that resection of a high-grade bladder tumor should not be performed coincident to TURP to avoid tumor seeding and possible intravasation of tumor cells likely to metastasize.
*Despite anecdotal reports of low- grade tumors implanting in the prostatic urethra after simultaneous resection, this risk appears to be small
Laser Resection
The most significant complication of laser therapy is ____.
Forward scatter of laser energy to adjacent structures, resulting in perforation of a hollow, viscous organ such as overlying bowel.
**Limiting energy to 35 W precludes exceeding 60°C on the outer bladder wall, minimizing the risk of perforation
Many patients with ____ can be managed safely in the office setting with use of diathermy or laser ablation.
Small (typically <0.5–1 cm), low-grade recurrences
** Instillation of viscous or injectable 1% to 2% lidocaine mixed with bicarbonate through a catheter and a dwelling time of 15 to 30 minutes yields mucosal analgesia, although pain with fulguration of 1- to 5-mm tumors is often acceptable without analgesia.
*** many small, low-grade tumors can be safely observed until they exhibit significant growth because of the minimal risk of progression
BLC: _____ accumulate preferentially in neoplastic tissue. Under blue light they emit red fluorescence.
Dye: _____
Photoactive porphyrins
Hexaminolevulinic acid
***When blue light technology is used, small papillary tumors and almost one-third more cases of CIS overlooked on cystoscopy are identified
NBI: NBI light is composed of two specific wavelengths that are absorbed by hemoglobin; ____ penetrates only the superficial mucosal layers, whereas _____ penetrates more deeply.
Dye: _____
415-nm light = superficial mucosal layers
540-nm light = deeper layers
Dye: NONE
*** Narrow band imaging (NBI) is an optical image enhancement technology intended to improve the visibility of blood vessels inherent to neoplastic processes.
- Initial studies suggest that about 13% more tumors could be diagnosed by NBI
It is believed that _____ immediately after transurethral resection is responsible for many early recurrences.
Initial tumors are most commonly found on the ____ of the bladder, whereas recurrences are often located near ____ as a result of “flotation”.
Thus intravesical chemo- therapy to kill such cells before implantation has been used for decades.
Tumor cell implantation
Initial tumors: floor and lower sidewalls
Recurrences: near the dome, due to “flotation”
____ appears to be the most effective adjuvant intravesical chemotherapeutic agent perioperatively.
A single dose administered within ____ lessens recurrence rates, whereas a dose ____ does not
Mitomycin C (MMC) Within 6 hours lessens recurrences 24 hours later does NOT
** MMC maintenance therapy does NOT reduce the risk further (therefore, walang MMC maintenance)
Phase III RCT by SWOG: Gemcitabine demonstrated a _____% reduction in the likelihood of tumor recurrence with a very favorable side-effect profile. Hence gemcitabine remains an alternative option for perioperative intravesical chemotherapy.
34% reduction
Although _____ are the most common complications of postoperative instillation.
Chemotherapy should be withheld in patients with _____.
BCG can NEVER be safely administered immediately after TUR because the ____.
Local irritative symptoms
Extensive resection or when there is concern about perforation.
BCG immediately after TUR: Risk of bacterial sepsis and death is high.
Intravesical BCG: Treatments are typically started _____ after tumor resection, allowing time for re-epithelialization of the bladder after TURBT, thereby minimizing the potential for intravasation of live bacteria.
A ____ is usually performed immediately before instillation.
In the event of a _____, the treatment should be delayed for at least several days.
2 to 4 weeks
UA, to further confirm absence of infection or significant bleeding to decrease the likelihood of systemic uptake of BCG.
Traumatic catheterization
BCG: After instillation, the patient should retain the solution for at least _____.
Some clinicians have advocated that the patient turn from side to side to bathe the entire urothelium, but there is _____.
_____ before instillation limits dilution of the agent by urine and facilitates adequate retention of the agent for 2 hours
1 to 2 hours
NO scientific support for this practice
Fluid, diuretic, and caffeine restriction
BCG Mechanism of Action: _____
Initial step: _____
Intravesical immunotherapy results in a robust local immune response characterized by induced expression of cytokines in the urine and bladder wall and by an influx of granulocytes and mononuclear and dendritic cells.
Initial step: direct BINDING TO FIBRONECTIN within the bladder wall, subsequently leading to direct stimulation of cell-based immunologic response and an antiangiogenic state.
BCG MOA: The observed pattern of cytokine induction with preferential upregulation of _____ reflects induction of a ____.
IFN-γ, IL-2, and IL-12
T-helper type-1 (Th1) response
** This immunologic response activates cell-mediated cytotoxic mechanisms believed to underlie the efficacy of BCG and other agents in the prevention of recurrence and progression
BCG tumor free response rates:
Initial: ____%
4 year durable response: ____%
10 years: ____%
BCG tumor free response rates:
Initial: 84%
4 year durable response: 50%
10 years: 30% free of tumor progression or recurrence
The current AUA guidelines panel recommends BCG as the preferred initial treatment option for _____ and as a potential option either up front or preferably after intravesical chemotherapy for _____.
High-risk bladder tumors
intermediate-risk tumors
Intravesical BCG can effectively treat residual papillary lesions but _____.
… should not be used as a substitute for surgical resection.
Impact of BCG:
Meta-analyses have concluded that BCG reduces ____.
The risk of progression
***Superior results with BCG were concentrated in trials using BCG maintenance therapy. In contrast, no chemotherapy trials have achieved a significant reduction in progression
SWOG Regimen:
__________
Estimated median recurrence-free survival was _____ in the maintenance arm and ____ in the control arm.
6-week induction course followed by 3 weekly instillations at 3 and 6 months and every 6 months thereafter for 3 years.
- 8 months
vs. - 7 months
Short-term use of a _____ such as _____ for 24 to 48 hour post-BCG can reduce the cystitis-related side effects of BCG instillation in up to ____% of patients with the most significant reduction in side effects grade II or higher seen in patients after the fourth instillation.
Quinolone antibiotic, such as ofloxacin or prulifloxacin
20%
Post-instillation use of quinolones also reduced treatment delays and discontinuations while not affecting recurrence or progres- sion rates.
- Many urologists use this routinely as part of BCG instillation protocol
ABSOLUTE Contraindications to BCG Therapy (6)
ABSOLUTE Contraindications to BCG Therapy (6)
Immunosuppressed and immunocompromised patientsa Immediately after transurethral resection on the basis of the risk
of intravasation and septic death
Personal history of BCG sepsis
Gross hematuria (intravasation risk)
Traumatic catheterization (intravasation risk) Total incontinence (patient will not retain agent)
RELATIVE Contraindications to BCG Therapy (5)
RELATIVE Contraindications to BCG Therapy (5)
Urinary tract infection (intravasation risk)
Liver disease (precludes treatment with isoniazid if sepsis
occurs)
Personal history of tuberculosis (risk theorized but unknown) Poor overall performance status
Advanced age
Management of BCG Toxicity: GRADE 1
Mild or moderate irritative voiding symptoms, mild hematuria,
fever <38.5°C
Assessment
Possible urine culture to rule out bacterial urinary tract infection
Symptom Management
Anticholinergics, topical antispasmodics (phenazopyridine), analgesics, nonsteroidal anti-inflammatory drugs
(Asymptomatic prostatic granulomas that occur after
BCG therapy can occasionally mimic prostate
cancer clinically and/or radiographically. There is
no evidence to support treatment in this setting
Management of BCG Toxicity: GRADE 2
Severe irritative voiding symptoms, hematuria, or symptoms
lasting >48 h
All maneuvers for grade 1, plus the following:
Assessment
Urine culture, chest radiograph, liver function tests
Management
Consider dose reduction to one-half to one-third of dose when instillations resume.
Treat culture results as appropriate.
Can also consider pre-treating with a single dose of isoniazid
before each subsequent instillation
Antimicrobial Agents
Administer isoniazid and rifampin orally until symptom resolution.
Also use vitamin B6 or pyridoxine.
Do not use monotherapy.
Observe for rifampin drug-drug interactions (e.g., warfarin). Monitor liver function tests.
Management of BCG Toxicity: GRADE 3
Allergic Reactions (Joint Pain, Rash)
Perform all maneuvers described for grades 1 and 2, plus the
following:
Isoniazid and rifampin, depending on response. Also use vitamin B6 or pyridoxine.
Solid Organ Involvement (Liver, Lung, Kidney)
Stop BCG instillations. Initiate antimycobacterial therapy with isoniazid, rifampin. If symptoms persist, consult with Infectious Disease specialist with expertise in anti- tuberculous therapy. Can add ethambutol.
Cycloserine often causes severe psychiatric symptoms and is to be strongly discouraged.
BCG is almost uniformly resistant to pyrazinamide, so this drug has no role.
Consider prednisone when response is inadequate or for septic shock (never given without effective antibacterial therapy).
_____ is the only chemotherapeutic agent approved by the FDA specifically for the intravesical treatment of papillary bladder cancer.
Thiotepa (triethylenethiophosphoramide)
** In the NCCN Guidelines, it is NOT recommended (does not appear to be effective).
_____ is anthracycline antibiotic that acts by binding DNA base pairs, inhibiting topoisomerase II, and inhibiting protein synthesis.
Doxorubicin (Adriamycin)
** In a review, doxorubicin demonstrated a 13% to 17% improvement over TUR in preventing recurrence but no advantage in preventing tumor progression (15.2% vs. 12.6%)
____ is a semisynthetic analogue of doxorubicin that was approved by the FDA for treatment of BCG-refractory CIS in patients who cannot tolerate cystectomy;
Valrubicin
** In a cohort of 90 patients with BCG-refractory CIS, only 21% demonstrated a complete response.
Optimization of MMC delivery can result in halving of the recur- rence rate in some studies.
What are the ways to optimize MMC delivery?
Eliminating residual urine volume
Fasting overnight
Sodium bicarbonate to reduce drug degradation
Increasing concentration to 40 mg in 20 mL
Electromotive intravesical MMC (4-7 fold improvement in delivery)
Synergo-RITE (intravesical heating/chemohyperthermia)
Hyperthermic intravesical chemotherapy (HIVEC)
Electromotive intravesical MMC
The electromotive current is usually delivered as a pulsed current of 40 to 60 mA/sec to a maximum of 20 mA over 30 minutes through two cathode electrodes placed over the gel-smeared skin of the lower abdominal wall.
Synergo-RITE
Heating the bladder along with mitomycin instillation to incite a mild inflam- mation of the bladder wall, which potentiates the action of mitomycin but can also improve the effectiveness of BCG.
The interior of the bladder can be heated to a temperature of about 42°C using radiofrequency needles emerging from the tip of a urethral catheter.
Intravesical heating enhances the absorption and activity of mitomycin C similar to when the electric current is delivered transabdominally.
HIVEC
Hyperthermic intravesical chemotherapy (HIVEC) can be delivered using the Bladder Recirculation System (BRC).
Involves instilling a solution of mitomycin that is heated to 42°C into the bladder in the form of a continuously recirculating irrigation.
Combination/sequential therapy: Gemcitabine + Mitomycin
Gemcitabine is instilled first at a dose of 1000 mg and left in place for 60 to 90 minutes —> DRAIN —> mitomycin C in the dose of 40 mg for another 60 to 90 minutes.
It is important to instill the mitomycin second because it is a vesicant (irritant), and irritation caused by the mitomycin can make it hard for the patient to retain the gemcitabine as well as resulting in significantly greater local side effects.
There is a high positive predictive value with cystoscopy because _____
The endoscopic appearance cannot reliably predict tumor stage or grade, although _____ and _____ suggests high-grade disease likely to be invasive.
Most lesions believed to be malignant are proven so pathologically.
Sessile morphology and/or the presence of necrosis
Surveillance cystoscopy:
____ and ____ on initial resection (single or multiple) provide the most predictive information with regard to recurrence in several studies.
____ on the 3-month surveillance cystoscopy in patients with Ta low-grade tumors is associated with recurrence rates so low that annual cystoscopy appears safe even at that point (beginning 12 months after the initial resection)
Tumor recurrence on initial 3-month cystoscopy and number of tumors
Absence of recurrence
Its ____ is the most important feature of cytology because a positive reading regardless of cystoscopic or radiographic findings suggests ____.
High specificity
The existence of malignancy in the vast majority of patients.
BTA stat (qualitative) BTA TRAK (quantitative)
Detect human complement factor H–related protein.
The overall sensitivity of these tests ranges from 50% to 80%, whereas the specificity is between 50% and 75%.
These tests are more sensitive than cytology particularly for low-grade tumors, but their results can be falsely positive in patients with inflammation, infection, or hematuria
ImmunoCyt
A hybrid of cytology and an immunofluorescence assay. Three fluorescent-labeled monoclonal antibodies are targeted at a UC variant of carcinoembryonic antigen and two bladder mucins.
Sensitivity and specificity are reported to be 86% and 79%, respectively.
May be helpful in adjudicating atypical cytology because it has a high negative predictive value in this setting
NMP22 BladderChek Test
Detection of nuclear matrix protein 22, part of the mitotic apparatus released from urothelial nuclei on cellular apoptosis.
The sensitivities and specificities range from 68.5% to 88.5% for sensitivity and from 65.2% to 91.3% for specificity
Benign conditions of the urinary tract such as stones, infection, inflammation, hematuria, and cystoscopy can cause a false-positive reading
UroVysion
Cytology-based test that uses FISH of DNA probes or labels specifically chosen to identify certain chromosomal foci.
Sensitivity for cytology compared with FISH of 19% versus 58% for grade 1, 50% versus 77% for grade 2, and 71% versus 96% for grade 3.
Notably, cytology detected only 67% of patients with CIS versus 100% detection by FISH in comparative studies.
***UroVysion has the highest specificity of the available tumor markers
CxBladder Monitor
Noninvasive urine monitoring test using gene expression and clinical patient data to generate a test to assess for evidence of urothelial carcinoma.
Shown to outperform other studies such as cytology and NMP22 with a sensitiv- ity of 91% and negative predictive value of 96%
Current AUA guidelines discourage the use of urinary markers to _____.
They do, however, suggest consideration of urinary markers to _____.
Replace cytology for surveillance of NMIBC.
Assess response to intravesical therapy as well as for the adjudication of atypical or equivocal cytology results
AUA guidelines suggest that clinicians should not perform routine surveillance upper tract imaging in ____.
In the setting of _____ guidelines suggest consideration of surveillance upper tract imaging at 1- to 2-year intervals, but there are few data evaluating the benefit of such imaging
Asymptomatic patients with a history of low-risk NMIBC.
Intermediate- or high-risk patients,
Although infrequent, the appearance of upper tract disease is associated with _____.
mortality rates of 40% to 70%.
Secondary tumor involvement of the prostatic urethra and ducts by UC may be detected in _____ of patients with high-risk non–muscle-invasive disease within 5 years and in _____ within 10 years
10% to 15%
20% to 40%
Lifestyle Changes as Secondary Prevention Strategies:
Smoking cessation, increased fluid intake, and a low-fat diet may reduce the risk of recurrence.
Increased hydration reduces the concentration and dwell time of carcinogens and thereby reduces the risk of malignant transformation within the urothelium
What are the demographics of NMIBC?
Caucasian american men (3:1) older than 65 years of age
What are the risk factors for bladder cancer?
Tobacco smoking Aromatic amines polycyclic hydrocarbons Arsenic Cyclophosphamide
Lynch syndrome
Schistosoma hematobium (sqaumous cell) Aristocholic acid (upper tracts)
What are some common mutations of tumor suppressor genes found in NMIBC?
GSTM-1 NAT-2 P16 CDKN2A PTEN RB1 TP53
What are some oncogene mutations seen in NMIBC?
FGFR3
PIK3CA
RAS
What is the rate of urinary tract malignancy in patient with asymptomatic microscopic hematuria?
2.6%
What are the common presenting symptoms of NMIBC?
Hematuria
irritative voiding symptoms
What is Ta bladder cancer?
Non invasive papillary carcinoma
What is Tis bladder cancer?
Carcinoma in situ
What is T1 bladder cancer?
Tumor invades the lamina propria
What is T2a bladder cancer?
Tumor invades the muscularis propria inner half
What is T2b bladder cancer?
Tumor invades deep muscularis propria (outer half)
What is T3a bladder cancer?
Tumor invades perivesical fat microscopically
What is T3b bladder cancer?
Tumor invades perivesical fat macroscopically
What is T4a bladder cancer?
Tumor invades adjacent organs
What is T4b bladder cancer?
Tumor invades pelvic side wall.
What is the 10 year survival prognosis for high grade NMIBC?
70-85%
What are the recurrence and progression rates for Ta NMIBC?
Recurrence: 55%
Progression: 6%
What are the recurrence and progression rates for T1 high grade NMIBC?
Recurrence: 45%
Progression: 17%
What defines low risk NMIBC?
Low grade
Solitary lesion
Ta < 3cm
Papillary urothelial neoplasm of low malignant potential
What defines intermediate risk NMIBC?
Recurrent low grade Ta within 1 year Solitary LG Ta > 3cm Multifocal LG Ta HG Ta < 3cm LG T1
What defines high risk NMIBC?
HG T1
Recurrent HG Ta
HG Ta > 3cm or multifocal
CIS
BCG failure in HG patient
Any variant histology
LVI
HG prostatic urethral involvement
How should NMIBC be diagnosed?
By thorough cystoscopy.
What should be the initial treatment of NMIBC?
At initial diagnosis of a patient with bladder cancer, a clinician should perform complete visual resection of the bladder tumor(s), when technically feasible
What should be included in addition to cystoscopy for evaluation of hematuria or a suspected bladder tumor?
Upper tract imaging.
What should be done if a patient has a normal cystoscopy but positive cytology?
Prostatic urethral biopsies Upper tract imaging Ureteroscopy Blue light cystoscopy Random bladder biopsies
What should be done if NMIBC shows variant histology?
Repeat TURBT in 4-6 weeks.
What is the rate of muscle invasion with variant histology?
86%
What is the preferred tx option for NMIBC with variant histology?
Due to the high rate of upstaging associated with variant histology, a clinician should consider offering initial radical cystectomy
What are the 5 FDA approved tumor markers?
NMP22 BTA Urovysion FISH Immunocyt Cxbladder
What is the role of urinary biomarkers in NMIBC?
In surveillance of NMIBC, a clinician should not use urinary biomarkers in place of cystoscopic evaluation.
What is the role of urinary biomarkers during surveillance for low risk NMIBC?
In a patient with a history of low-risk cancer and a normal cystoscopy, a clinician should not routinely use a urinary biomarker or cytology during surveillance.
What is the indication for urinary biomarkers in NMIBC?
In a patient with NMIBC, a clinician may use biomarkers to assess response to intravesical BCG (UroVysion® FISH) and adjudicate equivocal cytology (UroVysion® FISH and ImmunoCyt™). (Expert Opinion)
What should be done for a patient with NMIBC who underwent an incomplete initial resection?
Repeat TURBT if feasible.
What is the next step for high risk, high grade, Ta tumors after resection?
Repeat TURBT in 6 weeks.
What percentage of T1 tumors get upstaged?
30%
What is the next step after resection of a T1 NMIBC?
Repeat TURBT in 6 weeks.
What percentage of high grade Ta NMIBC get upstaged?
15%
What percentage of high grade Ta NMIBC have residual tumor?
50%
How big share of bladder cancer is non-muscle invasive?
~75%
How common is recurrence of non-muscle invasive bladder cancer?
~70%
What is the mortality of muscle-invasive bladder cancer?
50% dead in 5 years
The layers of the bladder wall:
urothelium
lamina propria
muscularis propria
perivesical tissue
What share of non-muscle invasive bladder cancer will progress?
~10-30%
What share of bladder cancer is caused by occupations exposure (industrialized contries)?
~5-10%
How high is the sensivity and specificity for cytology in bladder cancer?
Sensivity 12-48%
Specificity 87-95%
Are there any urinary markers that you can use for screening of bladder cancer?
NOT YET when compared to cystoscopy
How big share of CIS will progress to invasive bladder cancer?
> 30%
What is the effect of single intravesical instillation of chemotherapy on solitary TaG1-2, <3cm no CIS?
Almost halves the recurrence rate
What is the goal of TURB?
To perform a complete resection and make a correct diagnosis
When is a biopsy of the prostatic urethra indicated?
Multifocality
CIS
Visible abnormalities in the prostate
On all re-TUR
What are the befefits of photodynamic diagnosis in patients with non-muscle invasive bladder cancer?
improves the detection of CIS
lower cancer-specific motality
can help avoid perioperative single dose chemotherapy
What is the challenge with identifying variant histology of urothelial carcinoma?
It can be mistaken for reactive processes or benign tumours
Give four examples of variant histology of urothelial carcinoma:
Micropapillary variant
Sarcomatoid carcinoma
Plasmacytoid variant
Small cell carcinoma
What characterizes Micropapillary variant of urothelial carcinoma?
Aggressive behaviour with high metastatic rate
95% are muscle-invasive at time of presentation
What characterizes Sarcomatoid carcinoma of urothelial carcinoma?
No difference in survival when compared stage-for-stage with UrCa
BUT
70% of patients die within 2 years because of high stage
What characterizes Plasmocytoid variant of urothelial carcinoma?
Locally infiltative & highly aggressive
Unique pattern of spread along the ureter
Chemo-sensitive but very poor prognosis
What characterizes Small cell carcinoma of urothelial carcinoma?
Identical to undiffirentiated small-cell cancer of the lung
Associated with paraneoplatsic syndromes
High stage at presentation
50% disseminated disease with metastases to the brain and bone
5-year survival 16-29% (?) very poor prognosis
How to accomplish smoking cessation?
A 2-3 min consultation on smoking increases the probability of smoking cessation by 60% (from 3-5%)
Nicotine substitutes
Motivational interviewing
Medicins: Bupropion and Vareniklin
What is the effect of adjuvant intravesical chemotherapy instillations for intermediate risk tumours?
Reduce recurrence- but NOT progression- rates
What is the proper management of pT1 after first TurB?
second resection TurB
and BCG for 1-3 years
BCG contraindications:
Within 2 weeks fo TURB
Visible haematuria
After traumatic catheterisation
Symptomatic urinary tract infection
Bladder cancer
TX
Primary tumour can not be assessed
Bladder cancer
T0
No evidence of primary tumour
Bladder cancer
Ta
Non-invasive papillary carcinoma
Bladder cancer
Tis
Carcinoma in siut: “flat tumour”
Bladder cancer
T1
Tumour invades subepithelial connective tissue
Bladder cancer
T2
Tumour invades muscle
Bladder cancer
T2a
Tumour invades superficial muscle (inner half)
Bladder cancer
T2b
Tumour invades deep muscle (outer half)
Bladder cancer
T3
Tumour invades perivesical tissue
Bladder cancer
T3a
Tumour invades perivesical tissue microskopically
Bladder cancer
T3b
Tumour invades perivesical tissue macroscopically ( extravesical mass)
Bladder cancer
T4
Tumour invades any of the following: prostate stroma, seminal vesicles, uterus, vagina pelvic wall, abdominal wall
Bladder cancer
T4a
Tumour invades prostate stroma, seminal vesicles, uterus or vagina
Bladder cancer
T4b
Tumour invades pelvic wall or abdominal wall
Bladder cancer
NX
Regional lymph nodes can not be assessed
Bladder cancer
N0
No regional lymph node metastasis
Bladder cancer
N1
Metastasis in a single lymph node in the true pelvis (hypogastric, obturator, external iliac or presacral)
Bladder cancer
N2
Metastasis in multiple regional lymph nodes in the true pelvis (hypogastric, obturator, external iliac or presacral)
Bladder cancer
N3
Metastasis in common iliac lymph node(s)
Bladder cancer
M0
No distant metastasis
Bladder cancer
M1a
Non-regional lymph nodes
Bladder cancer
M1b
Other distant metastases
