Bladder Cancer: Diagnosis and Evaluation: Difference between revisions

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'''See [[Microscopic Hematuria (2020 AUA Guidelines)|2020 AUA Microscopic Hematuria Guideline Notes]]'''

'''See [[CUA & AUA: Non-muscle Invasive Bladder Cancer (2021 CUA & ~~2020~~ AUA)|~~2020~~ AUA Non-Muscle Invasive Bladder Cancer Guideline Notes]]'''

'''See [[CUA & AUA: Non-muscle Invasive Bladder Cancer (2021 CUA & 2024 AUA)|2024 AUA Non-Muscle Invasive Bladder Cancer Guideline Notes]]'''

'''See [[CUA & AUA: Non-muscle Invasive Bladder Cancer (2021 CUA & 2020 AUA)|2021 CUA Non-Muscle Invasive Bladder Cancer Guideline Notes]]'''

'''See [[AUA & ASCO & ASTRO & SUO: Muscle-invasive Bladder Cancer (~~2020~~)|~~2020~~ AUA Muscle-Invasive Bladder Cancer Guideline Notes]]'''

'''See [[AUA & ASCO & ASTRO & SUO: Muscle-invasive Bladder Cancer (2024)|2024 AUA Muscle-Invasive Bladder Cancer Guideline Notes]]'''

'''See [[CUA: Muscle-invasive Bladder Cancer (2019)|2019 CUA Muscle-Invasive Bladder Cancer Guideline Notes]]'''

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*'''Atypical cytology'''

** '''15% have cancer'''

* '''Causes of false-positive urine cytology'''

* '''Causes of false-positive/atypical urine cytology'''

*# '''UTI'''

*# '''Inflammation'''

*# '''Foreign body'''

*# '''Previous BCG'''

*# '''Radiation'''

*# '''Radiation[https://pubmed.ncbi.nlm.nih.gov/38661067/]'''

*# '''Chemotherapy'''

*# '''Contrast'''

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== Imaging ==

=== ~~~~Upper ~~urinary tract imaging~~ ===

=== Upper Urinary Tract ===

* '''2021 CUA NMIBC Guidelines: Upper urinary tract imaging is recommended in the initial workup of patients suspected to have bladder cancer'''

* '''2016 AUA NMIBC Guidelines: A clinician should perform upper urinary tract imaging as a component of the initial evaluation of a patient with bladder cancer'''

** Campbell’s: patients with solitary or limited low-grade Ta lesions do not need imaging unless they have concomitant hematuria, owing to the very low risk of extravesical disease

** The timing of initial upper tract imaging for bladder cancer is not clear, but it should likely be risk stratified and generally within 6 months of initial diagnosis.

* '''Upper tract imaging is usually performed before TUR to identify:'''

** '''Other sources of hematuria'''

** '''Assess the extravesical urothelium because of the “field change” nature of urothelial carcinoma'''

*** '''In patients with a known history of bladder cancer, upper tract tumors occur in <5% of patients'''

**** The overall incidence of significant findings with imaging of the upper tracts in patients with newly diagnosed bladder cancer is low but increases with tumors of the trigone, CIS, and high-risk disease.

**'''Although it is optimal to obtain cross-sectional imaging before TUR, if imaging is obtained subsequently, it should be delayed ≈7 days post-procedure to minimize inflammatory artifact,''' which can be mistaken for T3 disease

* '''Modality'''

**'''Contrast-based axial imaging, such as CT or MRI are recommended.'''

*** The sensitivity and specificity of CT in detecting nodal metastasis ranges from 31-50% and 68%-100%, respectively

*** MRI is generally considered to be more accurate than CT in detecting local tumor stage; however, reports vary in the literature

*** Retrograde pyelogram and intravenous urography may also be used when CT or MRI are unavailable.

*** US alone may not provide sufficient anatomic detail for upper urinary tract imaging during the work-up of bladder cancer

* '''~~Findings~~'''

==== Indications ====

** '''Hydronephrosis on cross-sectional imaging is suspicious for muscle invasion/extravesical disease'''

===== 2016 AUA/2021 CUA =====

* '''Recommended (1):'''

*# '''In the initial workup of all patients suspected to have bladder cancer'''

==== Rationale (2) ====

# '''Identify other sources of hematuria'''

# '''Assess the extravesical urothelium because of the “field change” nature of urothelial carcinoma'''

#* '''In patients with a known history of bladder cancer, upper tract tumors occur in <5% of patients'''

#** The overall incidence of significant findings with imaging of the upper tracts in patients with newly diagnosed bladder cancer is low but increases with tumors of the trigone, CIS, and high-risk disease.

==== Timing ====

* Optimal timing not clear, should likely be risk stratified and generally within 6 months of initial diagnosis.

* '''Usually performed before transurethral resection'''

**If imaging is obtained after transurethral resection, it should be delayed ≈7 days post-procedure to minimize inflammatory artifact, which can be mistaken for T3 disease

===== Modality =====

*'''Contrast-based axial imaging, such as CT or MRI are recommended.'''

** The sensitivity and specificity of CT in detecting nodal metastasis ranges from 31-50% and 68%-100%, respectively

** MRI is generally considered to be more accurate than CT in detecting local tumor stage; however, reports vary in the literature

** Retrograde pyelogram and intravenous urography may also be used when CT or MRI are unavailable.

** US alone may not provide sufficient anatomic detail for upper urinary tract imaging during the work-up of bladder cancer

===== Findings =====

* '''Hydronephrosis on cross-sectional imaging is suspicious for muscle invasion/extravesical disease'''

=== Lower urinary tract imaging ===

===== Modality =====

* MRI is superior to CT at tissue-contrast and staging muscle-invasive vs. non-muscle invasive disease

* ~~MRI protocol~~ includes: T2WI, DWI, contrast enhanced T1

====== MRI ======

* Protocol includes: T2WI, DWI, contrast enhanced T1

** Muscle is dark on T2

** False positive changes on MRI: BCG changes, post-TUR

** T3 tumor has spiculated appearance on MRI

* Furosemide can be given to help distend the ureter and bladder and potentially improve staging

* Vesical Imaging Reporting and Data System (VI-RADS)

** A 5-point scale used to standardize the interpretation and reporting of bladder cancer on multiparametric magnetic resonance imaging

=== Positron emission tomography and CT (PET/CT) ===

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===== Fluorescent (blue light) cystoscopy[https://www.ncbi.nlm.nih.gov/pubmed/17499283][https://www.ncbi.nlm.nih.gov/pubmed/17499291] =====

* '''A photosensitizing agent, 5-aminolevulinic acid (ALA) or hexyl aminolevulinic acid (HAL), is instilled into the bladder''' ~~before the procedure for 1-4 hours~~

** HAL is approved for use both in Europe and the United States, but currently does not have Health Canada approval

====== Rationale ======

* '''~~The photosensitizing agent is~~ metabolized to protoporphyrn IX by tumor cells, emitting a red fluorescence under blue light'''

* '''Improves detection of both small papillary tumors and CIS'''

* '''Blue light cystoscopy improves detection of both small papillary tumors and CIS'''

** Sensitivity for CIS 87% compared to 83% with white light

====== Mechanism of Action ======

** '''Relatively high false-positive rate'''

* '''A photosensitizing agent, 5-aminolevulinic acid (ALA) or hexyl aminolevulinic acid (HAL), is instilled into the bladder and subsequently''' '''metabolized to protoporphyrn IX by tumor cells, emitting a red fluorescence under blue light'''

* ~~Also reduces~~ the rate of residual tumour by 20% compared to white light cystoscopy

====== Efficacy ======

* Sensitivity for CIS 87% compared to 83% with white light

* '''Relatively high false-positive rate'''

* Reduces the rate of residual tumour by 20% compared to white light cystoscopy

* '''NCT02560584'''

** Population: 304 patients with a history of multiple, recurrent or high grade bladder tumors undergoing first surveillance cystoscopy

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**** 20% of recurrences seen only with blue-light flexible cystoscopy

** [https://pubmed.ncbi.nlm.nih.gov/29203268/ Daneshmand, Siamak, et al.] "Efficacy and safety of blue light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: a phase III, comparative, multicenter study." ''The Journal of urology'' 199.5 (2018): 1158-1165.

*'''PHOTO'''

**Population: 538 patients with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence

**Randomized to white light cystoscopy vs. blue light cytoscopy

**Primary outcome: time to recurrence at 3 years of follow-up

**Results

***Time to recurrence: no significant difference

***No significant difference in progression

**[https://pubmed.ncbi.nlm.nih.gov/38319866/ Heer, Rakesh, et al. "A randomized trial of PHOTOdynamic surgery in non–muscle-invasive bladder cancer." ''NEJM evidence'' 1.10 (2022): EVIDoa2200092.]

* '''Prospective studies have shown that blue light cystoscopy decreases recurrence rates, despite a trend in decreasing progression rates and prolong time to progression, current data is inconclusive, and impact on oncologic outcomes other than recurrence remains unclear'''

** '''Most clinical trials testing BLC have not used single dose chemotherapy at the time of TURBT, so the impact of combining both interventions remains uncertain.'''

* ~~'''Guideline perspective on role of fluorescent (blue light) cystoscopy:'''~~

*HAL is approved for use both in Europe and the United States, but currently does not have Health Canada approval

** '''CUA: can increase tumour detection at first TURBT and reduce recurrence risk.'''

** '''AUA: in a patient with NMIBC, blue light cystoscopy should be offered at the time of TURBT, if available, to increase detection and decrease recurrence'''

====== Indications ======

* '''2021 CUA: can increase tumour detection at first TURBT and reduce recurrence risk.'''

* '''2024 AUA: in a patient with NMIBC, blue light cystoscopy should be offered at the time of TURBT, if available, to increase detection and decrease recurrence'''

====== Technique ======

* The photosensitizing agent is instilled into the bladder 1-4 hours before the procedure

===== Narrow band imaging (NBI) =====

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*** Sampling of detrusor muscle is an important quality indicator (in tumours other than PUNLMP, LG Ta, and CIS), and its absence is associated with risk of under-staging, residual disease, and recurrence

*** '''Patients with presumed TaLG or CIS might be spared from muscle sampling at initial TURBT'''

== Stage at Diagnosis ==

* United States (SEER)[https://seer.cancer.gov/statistics-network/explorer/application.html?site=71&data_type=1&graph_type=2&compareBy=sex&chk_sex_3=3&chk_sex_2=2&rate_type=2&race=1&age_range=1&stage=101&advopt_precision=1&advopt_show_ci=on&hdn_view=0&advopt_show_apc=on&advopt_display=2]

** In situ: 48%

** Localized: 35%

** Regional: 7%

** Distant: 5%

** Unstaged: 5%

== Evaluation of Hematuria ==

@@ Line 2: / Line 2: @@
 '''See [[Microscopic Hematuria (2020 AUA Guidelines)|2020 AUA Microscopic Hematuria Guideline Notes]]'''
-'''See [[CUA & AUA: Non-muscle Invasive Bladder Cancer (2021 CUA & 2020 AUA)|2020 AUA Non-Muscle Invasive Bladder Cancer Guideline Notes]]'''
+'''See [[CUA & AUA: Non-muscle Invasive Bladder Cancer (2021 CUA & 2024 AUA)|2024 AUA Non-Muscle Invasive Bladder Cancer Guideline Notes]]'''
 '''See [[CUA & AUA: Non-muscle Invasive Bladder Cancer (2021 CUA & 2020 AUA)|2021 CUA Non-Muscle Invasive Bladder Cancer Guideline Notes]]'''
-'''See [[AUA & ASCO & ASTRO & SUO: Muscle-invasive Bladder Cancer (2020)|2020 AUA Muscle-Invasive Bladder Cancer Guideline Notes]]'''
+'''See [[AUA & ASCO & ASTRO & SUO: Muscle-invasive Bladder Cancer (2024)|2024 AUA Muscle-Invasive Bladder Cancer Guideline Notes]]'''
 '''See [[CUA: Muscle-invasive Bladder Cancer (2019)|2019 CUA Muscle-Invasive Bladder Cancer Guideline Notes]]'''
@@ Line 64: / Line 64: @@
 *'''Atypical cytology'''
 ** '''15% have cancer'''
-* '''<span style="color:#ff0000">Causes of false-positive urine cytology'''
+* '''<span style="color:#ff0000">Causes of false-positive/atypical urine cytology'''
 *# '''<span style="color:#ff0000">UTI'''
 *# '''<span style="color:#ff0000">Inflammation'''
 *# '''<span style="color:#ff0000">Foreign body'''
 *# '''<span style="color:#ff0000">Previous BCG'''
-*# '''<span style="color:#ff0000">Radiation'''
+*# '''<span style="color:#ff0000">Radiation[https://pubmed.ncbi.nlm.nih.gov/38661067/]'''
 *# '''<span style="color:#ff0000">Chemotherapy'''
 *# '''<span style="color:#ff0000">Contrast'''
@@ Line 93: / Line 93: @@
 == Imaging ==
-=== <span style="color:#ff0000">Upper urinary tract imaging</span> ===
+=== Upper Urinary Tract ===
-* '''<span style="color:#ff0000">2021 CUA NMIBC Guidelines: Upper urinary tract imaging is recommended in the initial workup of patients suspected to have bladder cancer</span>'''
-* '''<span style="color:#ff0000">2016 AUA NMIBC Guidelines: A clinician should perform upper urinary tract imaging as a component of the initial evaluation of a patient with bladder cancer</span>'''
-** Campbell’s: patients with solitary or limited low-grade Ta lesions do not need imaging unless they have concomitant hematuria, owing to the very low risk of extravesical disease
-** The timing of initial upper tract imaging for bladder cancer is not clear, but it should likely be risk stratified and generally within 6 months of initial diagnosis.
-* '''Upper tract imaging is usually performed before TUR to identify:'''
-** '''Other sources of hematuria'''
-** '''Assess the extravesical urothelium because of the “field change” nature of urothelial carcinoma'''
-*** '''In patients with a known history of bladder cancer, upper tract tumors occur in <5% of patients'''
-**** The overall incidence of significant findings with imaging of the upper tracts in patients with newly diagnosed bladder cancer is low but increases with tumors of the trigone, CIS, and high-risk disease.
-**'''Although it is optimal to obtain cross-sectional imaging before TUR, if imaging is obtained subsequently, it should be delayed ≈7 days post-procedure to minimize inflammatory artifact,''' which can be mistaken for T3 disease
-* '''Modality'''
-**'''Contrast-based axial imaging, such as CT or MRI are recommended.'''
-*** The sensitivity and specificity of CT in detecting nodal metastasis ranges from 31-50% and 68%-100%, respectively
-*** MRI is generally considered to be more accurate than CT in detecting local tumor stage; however, reports vary in the literature
-*** Retrograde pyelogram and intravenous urography may also be used when CT or MRI are unavailable.
-*** US alone may not provide sufficient anatomic detail for upper urinary tract imaging during the work-up of bladder cancer
-* '''Findings'''
+==== Indications ====
-** '''Hydronephrosis on cross-sectional imaging is suspicious for muscle invasion/extravesical disease'''
+===== 2016 AUA/2021 CUA =====
+* '''<span style="color:#ff0000">Recommended (1):</span>'''
+*# '''<span style="color:#ff0000">In the initial workup of all patients suspected to have bladder cancer</span>'''
+==== Rationale (2) ====
+# '''<span style="color:#ff0000">Identify other sources of hematuria'''
+# '''<span style="color:#ff0000">Assess the extravesical urothelium because of the “field change” nature of urothelial carcinoma'''
+#* '''In patients with a known history of bladder cancer, upper tract tumors occur in <5% of patients'''
+#** The overall incidence of significant findings with imaging of the upper tracts in patients with newly diagnosed bladder cancer is low but increases with tumors of the trigone, CIS, and high-risk disease.
+==== Timing ====
+* Optimal timing not clear, should likely be risk stratified and generally within 6 months of initial diagnosis.
+* '''Usually performed before transurethral resection'''
+**If imaging is obtained after transurethral resection, it should be delayed ≈7 days post-procedure to minimize inflammatory artifact, which can be mistaken for T3 disease
+===== Modality =====
+*'''Contrast-based axial imaging, such as CT or MRI are recommended.'''
+** The sensitivity and specificity of CT in detecting nodal metastasis ranges from 31-50% and 68%-100%, respectively
+** MRI is generally considered to be more accurate than CT in detecting local tumor stage; however, reports vary in the literature
+** Retrograde pyelogram and intravenous urography may also be used when CT or MRI are unavailable.
+** US alone may not provide sufficient anatomic detail for upper urinary tract imaging during the work-up of bladder cancer
+===== Findings =====
+* '''Hydronephrosis on cross-sectional imaging is suspicious for muscle invasion/extravesical disease'''
 === Lower urinary tract imaging ===
+===== Modality =====
 * MRI is superior to CT at tissue-contrast and staging muscle-invasive vs. non-muscle invasive disease
-* MRI protocol includes: T2WI, DWI, contrast enhanced T1
+====== MRI ======
+* Protocol includes: T2WI, DWI, contrast enhanced T1
 ** Muscle is dark on T2
 ** False positive changes on MRI: BCG changes, post-TUR
 ** T3 tumor has spiculated appearance on MRI
 * Furosemide can be given to help distend the ureter and bladder and potentially improve staging
+* Vesical Imaging Reporting and Data System (VI-RADS)
+** A 5-point scale used to standardize the interpretation and reporting of bladder cancer on multiparametric magnetic resonance imaging
 === <span style="color:#ff0000">Positron emission tomography and CT (PET/CT)</span> ===
@@ Line 146: / Line 162: @@
 ===== Fluorescent (blue light) cystoscopy[https://www.ncbi.nlm.nih.gov/pubmed/17499283][https://www.ncbi.nlm.nih.gov/pubmed/17499291] =====
-* '''<span style="color:#ff0000">A photosensitizing agent, 5-aminolevulinic acid (ALA) or hexyl aminolevulinic acid (HAL), is instilled into the bladder</span>''' before the procedure for 1-4 hours
-** HAL is approved for use both in Europe and the United States, but currently does not have Health Canada approval
+====== Rationale ======
-* '''<span style="color:#ff0000">The photosensitizing agent is metabolized to protoporphyrn IX by tumor cells,</span> emitting a red fluorescence under blue light'''
+* '''<span style="color:#ff0000">Improves detection of both small papillary tumors and CIS</span>'''
-* '''<span style="color:#ff0000">Blue light cystoscopy improves detection of both small papillary tumors and CIS</span>'''
-** Sensitivity for CIS 87% compared to 83% with white light
+====== Mechanism of Action ======
-** '''Relatively high false-positive rate'''
+* '''<span style="color:#ff0000">A photosensitizing agent, 5-aminolevulinic acid (ALA) or hexyl aminolevulinic acid (HAL), is instilled into the bladder and subsequently</span>''' '''<span style="color:#ff0000">metabolized to protoporphyrn IX by tumor cells,</span> emitting a red fluorescence under blue light'''
-* Also reduces the rate of residual tumour by 20% compared to white light cystoscopy
+====== Efficacy ======
+* Sensitivity for CIS 87% compared to 83% with white light
+* '''Relatively high false-positive rate'''
+* Reduces the rate of residual tumour by 20% compared to white light cystoscopy
 * '''<span style="color:#ff00ff">NCT02560584</span>'''
 ** Population: 304 patients with a history of multiple, recurrent or high grade bladder tumors undergoing first surveillance cystoscopy
@@ Line 162: / Line 182: @@
 **** 20% of recurrences seen only with blue-light flexible cystoscopy
 ** [https://pubmed.ncbi.nlm.nih.gov/29203268/ Daneshmand, Siamak, et al.] "Efficacy and safety of blue light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: a phase III, comparative, multicenter study." ''The Journal of urology'' 199.5 (2018): 1158-1165.
+*'''<span style="color:#ff00ff">PHOTO'''
+**Population: 538 patients with a suspected first diagnosis of NMIBC at intermediate or high risk for recurrence
+**Randomized to white light cystoscopy vs. blue light cytoscopy
+**Primary outcome: time to recurrence at 3 years of follow-up
+**Results
+***Time to recurrence: no significant difference
+***No significant difference in progression
+**[https://pubmed.ncbi.nlm.nih.gov/38319866/ Heer, Rakesh, et al. "A randomized trial of PHOTOdynamic surgery in non–muscle-invasive bladder cancer." ''NEJM evidence'' 1.10 (2022): EVIDoa2200092.]
 * '''Prospective studies have shown that blue light cystoscopy decreases recurrence rates, despite a trend in decreasing progression rates and prolong time to progression, current data is inconclusive, and impact on oncologic outcomes other than recurrence remains unclear'''
 ** '''Most clinical trials testing BLC have not used single dose chemotherapy at the time of TURBT, so the impact of combining both interventions remains uncertain.'''
-* '''<span style="color:#ff0000">Guideline perspective on role of fluorescent (blue light) cystoscopy:</span>'''
+*HAL is approved for use both in Europe and the United States, but currently does not have Health Canada approval
-** '''CUA: can increase tumour detection at first TURBT and reduce recurrence risk.'''
-** '''<span style="color:#ff0000">AUA:</span> in a patient with NMIBC, blue light cystoscopy <span style="color:#ff0000">should be offered at the time of TURBT, if available,</span> to increase detection and decrease recurrence'''
+====== Indications ======
+* '''2021 CUA: can increase tumour detection at first TURBT and reduce recurrence risk.'''
+* '''<span style="color:#ff0000">2024 AUA:</span> in a patient with NMIBC, blue light cystoscopy <span style="color:#ff0000">should be offered at the time of TURBT, if available,</span> to increase detection and decrease recurrence'''
+====== Technique ======
+* The photosensitizing agent is instilled into the bladder 1-4 hours before the procedure
 ===== Narrow band imaging (NBI) =====
@@ Line 186: / Line 220: @@
 *** Sampling of detrusor muscle is an important quality indicator (in tumours other than PUNLMP, LG Ta, and CIS), and its absence is associated with risk of under-staging, residual disease, and recurrence
 *** '''Patients with presumed TaLG or CIS might be spared from muscle sampling at initial TURBT'''
+== Stage at Diagnosis ==
+* United States (SEER)[https://seer.cancer.gov/statistics-network/explorer/application.html?site=71&data_type=1&graph_type=2&compareBy=sex&chk_sex_3=3&chk_sex_2=2&rate_type=2&race=1&age_range=1&stage=101&advopt_precision=1&advopt_show_ci=on&hdn_view=0&advopt_show_apc=on&advopt_display=2]
+** In situ: 48%
+** Localized: 35%
+** Regional: 7%
+** Distant: 5%
+** Unstaged: 5%
 == Evaluation of Hematuria ==