Bladder Cancer 2

Front 1

What percent of bladder tumors are non-muscle invasive (Ta, T1, and CIS) at presentation?

Back 1

70%, but Chapter 75 says 55-60%. (Of these, Ta = 70%, T1 = 20%, CIS = 10%)

Front 2

Is there a difference in the risk that a patient has for bladder cancer with gross hematuria versus microscopic hematuria?

Back 2

The patient with gross hematuria has a significantly higher risk of bladder cancer than a patient with microscopic hematuria. Microscopic hematuria is around 0.5-10.5% and gross hematuria is 13-34.5%.

Front 3

Other than hematuria, what other symptom is an indication for upper tract imaging and cystoscopy to rule out urothelial carcinoma?

Back 3

Unexplained irritative voiding symptoms

Front 4

Why must one be cautious even if a bladder tumor is characterized as non-muscle invasive after TUR?

Back 4

Understaging is frequent from specimens collected at TUR. After cystectomy, many tumors are found to be more extensive than indicated by the TUR specimen. This is especially true for tumors that appear to be stage T1. Understaging may occur as frequently as 34% to 62% of the time from TUR specimens.

Front 5

For non-muscle invasive tumors, what is the biggest predictor of stage-progression?

Back 5

The pathologic grade. CIS is the second most important prognostic factor.

Front 6

You are reviewing the path after a TURBT of a 65 year old female patient with her on the phone. This is her first TURBT and she was low grade Ta disease. What does this pathology mean for her? (in terms of follow-up, risk of recurrence, risk of progression)

Back 6

She obviously has a good result here. Her risk of recurrence is high, recurrence is the rule with bladder cancer. Her risk is around 50-70%. Her risk of progression is very low at around 5% for low grade Ta lesion.
Her f/u will be standard with cystoscopy every 3 months for the first year, followed by every 6 months for 2 years after that, then yearly after that.

Front 7

How would the above clinical scenario have changed if the patient had been T1, or high-grade Ta?

Back 7

First of all the patient would need to undergo a re-TURBT whether there was muscle in the specimen or not. Some patients will be upstaged at re-resection, but for others the patient with residual disease at re-resection has a significantly higher risk of progression at 5 years than the patient with no residual disease at re-resection. The patient should also be given Mitomycin C at the time of the re-resection.
This patient would then be offered intravesical therapy with BCG. The patient would get an induction course of 1 treatment a week for 6 weeks. The patient would then follow-up with screening cystoscopy every 3 months and cytology. If there was no evidence of recurrent disease the patient would then be offered maintenance BCG treatment which is a maintenance treatment every 6 months (3 courses) for 2-3 years…regimen we use here with Pruthi.
The patient with high grade T1 disease has a 30-50% chance of progression to muscle invasive disease. That patient’s chance of recurrence is as high as 80%.

Front 8

What are other factors in a patient besides grade and stage that might make them a higher risk patient in regards to the bladder cancer itself? In other words what other things might you want to know about a patient with high grade T1 disease that might make them high risk in regards specifically to their bladder cancer?

Back 8

Size of the lesion
Multiplicity of lesions
Status of the rest of the urothelium, in other words was CIS seen as well
Presence or absence of lymphovascular invasion on pathology specimen

Front 9

Why is CIS considered a precursor lesion for the development of invasive high-grade cancer?

Back 9

Between 40 - 83% of patients with CIS will go on to develop muscle invasive disease if untreated. In fact, 20% of patients thought to have CIS alone are found already to have muscle-invasive disease on final pathology after cystectomy.

Front 10

What complications should be discussed with patients before TURBT? What complication rate can you quote?

Back 10

The main complications include uncontrolled hematuria and clinically significant bladder perforation. These occur about 5% of the time.

Front 11

What can be done to minimize the risk of complication?

Back 11

Avoid bladder overdistention: Fill bladder only enough to visualize contents. This minimizes bladder wall movement and lessens thinning of the detrusor.
Use muscle-paralyzing agents: This minimizes the risk of the obturator reflex especially when resecting lateral wall tumors.
Resect large or bulky tumors in a staged manner: allows for safer resection of residual tumor if indicated

Front 12

Should you consider re-TURBT in a patient that you did a TURBT on a few weeks ago that pathology shows low grade Ta disease? You remember during the resection that you got almost all of the lesion but there was a small amount that was difficult to reach and you didn’t resect all of it.

Back 12

Yes. This patient should have a re-resection.

Front 13

What are the theoretical advantages and risks associated with random biopsies at the time of TUR? Is this practice indicated?

Back 13

Since CIS may be found in normal appearing urothelium, random tissue biopsies at the time of TUR may uncover otherwise hidden CIS and consequently affect treatment of some patients. In one study, the practice of random biopsies in high-risk patients changed management in 7% of cases.
This must be weighed against the theoretical risk that biopsies provide an exposed bed allowing for tumor seeding in otherwise unaffected areas of the bladder or prostatic urethra.
The authors state that is practice is not indicated in low-risk patients (low-grade papillary tumors with negative cytology) but do not definitively state when it is indicated.

Front 14

What intravesical agent applied immediately after TUR has been show to reduce the recurrence rate of non-muscle-invasive bladder cancer by approximately 50%? What is its mechanism of action? Can BCG be used in this setting?

Back 14

Mitomycin C; works by killing off residual tumor cells dislodged by resection that might otherwise reimplant and contribute to early recurrence.
BCG should not be used in this setting due to the risk of systemic absorption, sepsis, and death.

Front 15

You are discussing with a patient the result of their TURBT specimen that shows high grade Ta disease. Is this non-invasive bladder cancer low or high risk?

Back 15

It is not as common to see high grade Ta disease but these lesions are thought to be high risk and should be monitored closely in accordance with the high grade

Front 16

What cytokines are preferentially upregulated in the immune response stimulated in the bladder after BCG therapy? Is the cell mediated response primarily Th1 or Th2?

Back 16

Interferon-γ and IL-2
Primarily Th1 response is induced that ultimately leads to cell-mediated cytotoxic mechanisms

Front 17

What is the initial response rate as well as the 4-year and 10-year disease free rates after using intravesical BCG following TURBT for non-muscle invasive bladder tumors? How does this compare to intravesical chemotherapy used after TURBT?

Back 17

80%, 50%, and 30% respectively
BCG has been shown to be significantly more efficacious than intravesical chemo

Front 18

Does BCG affect stage-progression?

Back 18

BCG has been shown in two separate meta-analyses to reduce the risk of progression by 23-27% with a median follow-up between 26-30 months. This was only seen in trials using BCG maintenance therapy.

Front 19

What are the contraindications to BCG therapy?

Back 19

Absolute: Immunosuppressed or immunocompromised, immediately after TUR, h/o BCG sepsis, gross hematuria, traumatic catheterization, total incontinence (patient will not retain agent)
Relative: UTI, liver disease (precludes treatment of isoniazid if sepsis occurs), h/o TB, poor overall performance status, advanced age
Theoretical: patients with prosthetic materials, ureteral reflux, anti-TNF meds (?predisposition to BCG sepsis)

Front 20

What is the optimal BCG treatment schedule?

Back 20

Has not been established.
Most authorities believe that a 6-week induction course followed by a maintenance course. Dr. Pruthi likes to do maintenance instillations at 6 month intervals for 3 weeks. So a patient might get induction BCG and then +/- repeat biopsy to determine initial effectiveness. That patient that would get screening cystoscopy at 3 months followed by 3 BCG treatments at some point after the cysto, then cysto in 3 months with nothing, then cysto 3 months later with BCG treatment after……and continue this for 1-3 years.

Front 21

Define the following terms: 1) BCG-refractory, 2) BCG-resistant, 3) BCG-relapsing.

Back 21

BCG-refractory = nonimproving or worsening disease after initial 6-week course
BCG-resistant = recurrence or persistence of lesser degree, stage, or grade after an initial course of BCG
BCG-relapsing = recurrence after initial resolution with BCG

Front 22

How long should one wait before declaring BCG failure in a patient?

Back 22

At least 6 months

Front 23

What is the treatment algorithm for patients who fail to respond to initial BCG or intravesical chemotherapy?

Back 23

After failure to respond to an initial course of BCG, a subsequent course is indicated in patients with lower risk of progression as 30% to 50% of patients will respond to the second course. However, failure to respond to an initial course of BCG is also cause to consider cystectomy in younger patients at higher risk of recurrence.
Failure to respond to a second course of BCG is an indication for immediate cystectomy as rapid disease progression is common in such patients. If the patient is unwilling or unable to undergo cystectomy, than investigational protocols or combination therapy should be considered.
This includes BCG + Interferon
If that then fails then proceed to intravesical gemcitabine

Front 24

Under what conditions should radical cystectomy be considered in for patients with clinically non-invasive bladder tumors?

Back 24

It should be considered for patients with non-muscle invasive bladder cancers that are high grade and invading deeply into lamina propria, exhibit lymphovascular invasion, are associated with diffuse CIS, are in diverticula, substantially involve the distal ureters or prostatic urethra, are refractory to initial therapy, and are too large or anatomically inaccessible to remove in their entirety endoscopically. It also can be used in patients who understand the risks and benefits of bladder preservation versus cystectomy and request definitive therapy.

Front 25

What upper tract imaging surveillance is recommended for low and high grade tumors?

Back 25

It’s not necessary for low-grade tumors but should be performed at diagnosis and every 1-2 years for high-grade tumors

Front 26

You see a patient in your clinic who has been diagnosed with bladder cancer s/p TURBT who had low grade low stage disease and so we are following him with cystoscopy at this point every 3 months. The cysto today looked normal but when you talk to him he is still smoking. At this point is there any benefit to stopping smoking or has the damage already been done?

Back 26

Even in those diagnosed with non‐invasive cancers initially the failure to quit smoking predicts an ominous course for those patients.

The risk that smoking poses for patients with regards to bladder cancer is a dose dependant risk and will decrease in those patients that stop smoking. One of the important things to remember however is that the risk does not decrease to baseline after smoking cessation until about 20 years after quitting.

Front 27

You are doing a survellience cysto on a patient with a history of bladder cancer s/p TURBT. They have a lesion on their bladder that is a velvety plaque concerning for CIS. You think in your mind that I need to set this patient up for bladder biopsy. Should you do anything at the time of the survelleince cysto?

What percentage of patients with CIS have positive cytology?

Back 27

Take cytology with barbitage while in the bladder. Cytopathology is positive in 80‐90% of patients with urinary CIS.

Front 28

You have a patient that had resection of a superficial high grade bladder cancer that was not muscle invasive based on pathology. This patient then returned to clinic with bone pain and on workup where found to have distant metastasis. What happened with this patient?

Back 28

According to the authors it is most likely that the patient was understaged or had another lesion at the time of resection that was unrecognized that became muscle invasive and caused the distant metastatic spread of the tumor.

If cystoscopy was done on this patient there would most likely by a new muscle invasive lesion identified.

Front 29

Why must one be cautious even if a bladder tumor is characterized as non-muscle invasive after TUR? In other words how common is understaging with TURBT?

Back 29

Understaging is frequent from specimens collected at TUR. After cystectomy, many tumors are found to be more extensive than indicated by the TUR specimen. This is especially true for tumors that appear to be stage T1. Understaging may occur as frequently as 34% to 62% of the time from TUR specimens.

Front 30

For non-muscle invasive tumors, what is the biggest predictor of stage-progression?

Back 30

The pathologic grade. CIS is the second most important prognostic factor.

Front 31

You are reviewing the path after a TURBT of a 65 year old female patient with her on the phone. This is her first TURBT and she was low grade Ta disease. What does this pathology mean for her? (in terms of follow-up, risk of recurrence, risk of progression)

Back 31

She obviously has a good result here. Her risk of recurrence is high, recurrence is the rule with bladder cancer. Her risk is around 50-70%. Her risk of progression is very low at around 5% for low grade Ta lesion.
Her f/u will be standard with cystoscopy every 3 months for 2 years, followed by every 6 months for 2 years after that, then yearly after that.

Front 32

Should you consider re-TURBT in a patient that you did a TURBT on a few weeks ago that pathology shows low grade Ta disease? You remember during the resection that you got almost all of the lesion but there was a small amount that was difficult to reach and you didn’t resect all of it.

Back 32

Yes. This patient should have a re-resection.

Front 33

What is the initial response rate as well as the 4-year and 10-year disease free rates after using intravesical BCG following TURBT for non-muscle invasive bladder tumors? How does this compare to intravesical chemotherapy used after TURBT?

Back 33

80%, 50%, and 30% respectively
BCG has been shown to be significantly more efficacious than intravesical chemo

Front 34

Does BCG affect stage-progression? Is this for any patient that just gets BCG or do they need to get induction plus maintenance?

Back 34

BCG has been shown in two separate meta-analyses to reduce the risk of progression by 23-27% with a median follow-up between 26-30 months. This was only seen in trials using BCG maintenance therapy.

Front 35

What are the contraindications to BCG therapy?

Back 35

Absolute: Immunosuppressed or immunocompromised, immediately after TUR, h/o BCG sepsis, gross hematuria, traumatic catheterization, total incontinence (patient will not retain agent)
Relative: UTI, liver disease (precludes treatment of isoniazid if sepsis occurs), h/o TB, poor overall performance status, advanced age
Theoretical: patients with prosthetic materials, ureteral reflux, anti-TNF meds (?predisposition to BCG sepsis)

Front 36

What is the optimal BCG treatment schedule?

Back 36

Has not been established.
Most authorities believe that a 6-week induction course followed by a maintenance course. Dr. Pruthi likes to do maintenance instillations at 6 month intervals for 3 weeks. So a patient might get induction BCG and then +/- repeat biopsy to determine initial effectiveness. That patient that would get screening cystoscopy at 3 months followed by 3 BCG treatments at some point after the cysto, then cysto in 3 months with nothing, then cysto 3 months later with BCG treatment after……and continue this for 1-3 years.

Front 37

Define the following terms: 1) BCG-refractory, 2) BCG-resistant, 3) BCG-relapsing.

Back 37

BCG-refractory = nonimproving or worsening disease after initial 6-week course
BCG-resistant = recurrence or persistence of lesser degree, stage, or grade after an initial course of BCG
BCG-relapsing = recurrence after initial resolution with BCG

Front 38

How long should one wait before declaring BCG failure in a patient?

Back 38

At least 6 months

Front 39

What is the treatment algorithm for patients who fail to respond to initial BCG or intravesical chemotherapy?

Back 39

*After failure to respond to an initial course of BCG, a subsequent course is indicated in patients with lower risk of progression as 30% to 50% of patients will respond to the second course. However, failure to respond to an initial course of BCG is also cause to consider cystectomy in younger patients at higher risk of recurrence.

*Failure to respond to a second course of BCG is an indication for immediate cystectomy as rapid disease progression is common in such patients. If the patient is unwilling or unable to undergo cystectomy, than investigational protocols or combination therapy should be considered.

*This includes BCG + Interferon
If that then fails then proceed to intravesical gemcitabine

Front 40

Under what conditions should radical cystectomy be considered in for patients with clinically non-invasive bladder tumors?

Back 40

It should be considered for patients with non-muscle invasive bladder cancers that are high grade and invading deeply into lamina propria, exhibit lymphovascular invasion, are associated with diffuse CIS, are in diverticula, substantially involve the distal ureters or prostatic urethra, are refractory to initial therapy, and are too large or anatomically inaccessible to remove in their entirety endoscopically. It also can be used in patients who understand the risks and benefits of bladder preservation versus cystectomy and request definitive therapy.

Front 41

You are seeing a patient in multidisciplinary clinic, a 73 year old male with high grade T1 disease on TURBT. When reviewing the records the pathologist states that there is no muscularis propria in the specimen. What should be the initial recommendation for this patient?

Back 41

This gentleman should undergo re-TURBT as there is no way to accurately stage this patient without muscle in the biopsy specimen.

Front 42

Why is CIS considered a precursor lesion for the development of invasive high-grade cancer? In other words what happens with CIS patients if you don't treat them?

Back 42

Between 40 - 83% of patients with CIS will go on to develop muscle invasive disease if untreated. In fact, 20% of patients thought to have CIS alone are found already to have muscle-invasive disease on final pathology after cystectomy.

Front 43

You are discussing with a patient the result of their TURBT specimen that shows high grade Ta disease. Is this non-invasive bladder cancer low or high risk?

Back 43

It is not as common to see high grade Ta disease but these lesions are thought to be high risk and should be monitored closely in accordance with the high grade.