Non-Muscle Invasive Bladder Cancer: Difference between revisions

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==== Immediate instillation following TURBT ====

* '''Commonly used intravesical agents for single post-operative intravesical instillation of chemotherapy ~~include~~ (5):'''

* '''Indications'''

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

**'''Particularly effective for the initial presentation of a (3):'''

**# '''Solitary'''

**# '''Low-grade'''

**# '''Papillary tumor'''

*** '''The incremental benefit in patients with recurrent or multiple tumors is limited.'''

*** '''No benefit has been found in patients with high-grade disease.'''

*** '''Given the number needed to treat of 8, some authors have suggested that intravesical chemotherapy reduces overall cost of care by reducing the need for secondary resections. However, subsequent studies have shown that the tumors prevented are primarily smaller tumors that are often treated in the office or ambulatory surgery setting so the economic impact regarding recurrences remains controversial if recurrences are treated in any manner other than inpatient care'''

*'''Contraindications'''

*# '''After extensive resection'''

*# '''Bladder perforation is suspected'''

*# '''Significant bleeding'''

*#*'''Saline irrigation might be a consideration for patients with low- and intermediate risk NMIBC post-TURBT when intravesical chemotherapy is contraindicated (e.g., extensive bladder resection) or unavailable (2021 CUA NMIBC Guidelines)'''

*'''Rationale'''

**'''Reduces risk of tumour recurrence (absolute risk reduction ≈12%); no benefit of chemotherapy on progression'''

*** '''BCG is the only agent shown to delay or reduce high-grade tumor progression.''' No chemotherapy trials have achieved a significant reduction in progression

*** '''Meta-analysis evaluating intravesical chemotherapy on risk of recurrence'''

**** 13 studies including 2548 patients

**** '''Intravesical chemotherapy''' prolonged recurrence-free interval by 38% (HR: 0.62; 95% confidence interval [CI], 0.50-0.77; p<0.001; I(2): 69%), '''and early recurrences were 12% less likely in the intervention population (ARR: 0.12'''; 95% CI, -0.18 to -0.06; p<0.001, I(2): 0%). '''The number needed to treat to prevent one early recurrences was 8''' (95% CI, 6-17 patients).

**** High risk of bias present in 12 of 13 publications. Quality of evidence for recurrence-free interval was very low and low for early recurrences.

**** Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. [https://pubmed.ncbi.nlm.nih.gov/29801011/ Perlis et. al.] Eur Urol. 2013 Sep;64(3):421-30.

** '''Mechanism of action'''

*** '''The two primary theories for recurrent tumor formation:'''

**** '''Genetic field defect exists with multiple new tumors spontaneously arising within the bladder'''

**** '''Local reimplantation of tumor cells after tumor resection'''

***** '''Tumor cell implantation immediately after resection may be responsible for many early recurrences, and this has been used to explain the observation that initial tumors are most commonly found on the floor and lower sidewalls of the bladder, whereas recurrences are often located near the dome as a result of “flotation”'''

***** '''Immediate instillation of intravesical chemotherapy may reducing tumor cell implantation'''

*** '''Intravesical chemotherapy may also have an ablative effect on small occult tumours'''

*'''Commonly used intravesical agents for single post-operative intravesical instillation of chemotherapy (5):'''

*# '''Gemcitabine''' (SWOG S0337[https://pubmed.ncbi.nlm.nih.gov/29801011/ §])

*##Mechanism of action: inhibits DNA synthesis

*##Dose: 2g in 100mL[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315602/]

*# '''Mitomycin C (MMC)'''

*##Mechanism of action: alkylating agent that inhibits DNA replication

*##Dose: 40g in 20-40mL

*# '''Doxorubicin'''

*# '''Epirubicin'''

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*** As per 11th Ed. Campbell’s, MMC appears to be the most effective adjuvant intravesical chemotherapeutic agent perioperatively, although epirubicin is used in Europe and direct comparative studies are lacking).

** '''Thiotepa has also been evaluated'''

* '''Reduces risk of tumour recurrence (absolute risk reduction ≈12%); no benefit of chemotherapy on progression'''

** '''BCG is the only agent shown to delay or reduce high-grade tumor progression.''' No chemotherapy trials have achieved a significant reduction in progression

** '''Meta-analysis evaluating intravesical chemotherapy on risk of recurrence'''

*** 13 studies including 2548 patients

*** '''Intravesical chemotherapy''' prolonged recurrence-free interval by 38% (HR: 0.62; 95% confidence interval [CI], 0.50-0.77; p<0.001; I(2): 69%), '''and early recurrences were 12% less likely in the intervention population (ARR: 0.12'''; 95% CI, -0.18 to -0.06; p<0.001, I(2): 0%). '''The number needed to treat to prevent one early recurrences was 8''' (95% CI, 6-17 patients).

*** High risk of bias present in 12 of 13 publications. Quality of evidence for recurrence-free interval was very low and low for early recurrences.

*** Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. [https://pubmed.ncbi.nlm.nih.gov/29801011/ Perlis et. al.] Eur Urol. 2013 Sep;64(3):421-30.

* '''Mechanism of action'''

** '''The two primary theories for recurrent tumor formation:'''

*** '''Genetic field defect exists with multiple new tumors spontaneously arising within the bladder'''

*** '''Local reimplantation of tumor cells after tumor resection'''

**** '''Tumor cell implantation immediately after resection may be responsible for many early recurrences, and this has been used to explain the observation that initial tumors are most commonly found on the floor and lower sidewalls of the bladder, whereas recurrences are often located near the dome as a result of “flotation”'''

**** '''Immediate instillation of intravesical chemotherapy may reducing tumor cell implantation'''

** '''Intravesical chemotherapy may also have an ablative effect on small occult tumours'''

* '''Particularly effective for the initial presentation of a (3):'''

*# '''Solitary'''

*# '''Low-grade'''

*# '''Papillary tumor'''

** '''The incremental benefit in patients with recurrent or multiple tumors is limited.'''

** '''No benefit has been found in patients with high-grade disease.'''

** '''Given the number needed to treat of 8, some authors have suggested that intravesical chemotherapy reduces overall cost of care by reducing the need for secondary resections. However, subsequent studies have shown that the tumors prevented are primarily smaller tumors that are often treated in the office or ambulatory surgery setting so the economic impact regarding recurrences remains controversial if recurrences are treated in any manner other than inpatient care'''

* '''Indications'''

** '''See''' '''[[CUA/AUA: Non-muscle Invasive Bladder Cancer (2021 CUA/2016 AUA))|2016 AUA/2021 CUA NMBIC]] Guideline Notes'''

* '''Contraindications'''

*# '''After extensive resection'''

*# '''Bladder perforation is suspected'''

*# '''Significant bleeding'''

*#*'''Saline irrigation might be a consideration for patients with low- and intermediate risk NMIBC post-TURBT when intravesical chemotherapy is contraindicated (e.g., extensive bladder resection) or unavailable (2021 CUA NMIBC Guidelines)'''

*'''Steps for Successful Perioperative Administration of Intravesical Chemotherapy'''

*# '''Include intent to administer perioperative chemotherapy (and agent) on actual operative schedule.'''

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*** '''Calcified eschars'''

*** '''Added difficulty of subsequent cystectomy'''

*** '''Serious sequelae and rare deaths have occurred, especially in patients with perforation during resection. Chemotherapy should be withheld in patients with extensive resection or when there is concern about perforation.'''

*** '''Serious sequelae and rare deaths have occurred, especially in patients with perforation during resection.'''

****'''Chemotherapy should be withheld in patients with extensive resection or when there is concern about perforation.'''

***'''Given side effects of MMC, consider preferential use of gemcitabine which is better tolerated'''

** '''Thiotepa'''

*** '''Local irritative symptoms'''

@@ Line 83: / Line 83: @@
 ==== Immediate instillation following TURBT ====
-* '''<span style="color:#ff0000">Commonly used intravesical agents for single post-operative intravesical instillation of chemotherapy include (5):</span>'''
+</span>
+* '''<span style="color:#ff0000">Indications</span>'''
+** <span style="color:#ff0000">'''See'''</span> '''[[CUA & AUA: Non-muscle Invasive Bladder Cancer (2021 CUA & 2020 AUA)|2020 AUA/2021 CUA NMBIC]] <span style="color:#ff0000">Guideline Notes</span>'''
+**'''<span style="color:#ff0000">Particularly effective for the initial presentation of a (3):</span>'''
+**# '''<span style="color:#ff0000">Solitary</span>'''
+**# '''<span style="color:#ff0000">Low-grade</span>'''
+**# '''<span style="color:#ff0000">Papillary tumor</span>'''
+*** '''<span style="color:#ff0000">The incremental benefit in patients with recurrent or multiple tumors is limited.</span>'''
+*** '''<span style="color:#ff0000">No benefit has been found in patients with high-grade disease.</span>'''
+*** '''Given the number needed to treat of 8, some authors have suggested that intravesical chemotherapy reduces overall cost of care by reducing the need for secondary resections. However, subsequent studies have shown that the tumors prevented are primarily smaller tumors that are often treated in the office or ambulatory surgery setting so the economic impact regarding recurrences remains controversial if recurrences are treated in any manner other than inpatient care'''
+*'''Contraindications'''
+*# '''After extensive resection'''
+*# '''Bladder perforation is suspected'''
+*# '''Significant bleeding'''
+*#*'''Saline irrigation might be a consideration for patients with low- and intermediate risk NMIBC post-TURBT when intravesical chemotherapy is contraindicated (e.g., extensive bladder resection) or unavailable (2021 CUA NMIBC Guidelines)'''
+*'''<span style="color:#ff0000">Rationale</span>'''
+**'''<span style="color:#ff0000">Reduces risk of tumour recurrence (absolute risk reduction ≈12%);</span> <span style="color:#ff0000">no benefit of chemotherapy on progression</span>'''
+*** '''BCG is the only agent shown to delay or reduce high-grade tumor progression.''' No chemotherapy trials have achieved a significant reduction in progression
+*** '''<span style="color:#ff00ff">Meta-analysis evaluating intravesical chemotherapy on risk of recurrence</span>'''
+**** 13 studies including 2548 patients
+**** '''<span style="color:#ff0000">Intravesical chemotherapy</span>''' prolonged recurrence-free interval by 38% (HR: 0.62; 95% confidence interval [CI], 0.50-0.77; p<0.001; I(2): 69%), '''<span style="color:#ff0000">and early recurrences were 12% less likely in the intervention population (ARR: 0.12'''</span>; 95% CI, -0.18 to -0.06; p<0.001, I(2): 0%). '''The number needed to treat to prevent one early recurrences was 8''' (95% CI, 6-17 patients).
+**** High risk of bias present in 12 of 13 publications. Quality of evidence for recurrence-free interval was very low and low for early recurrences.
+**** Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. [https://pubmed.ncbi.nlm.nih.gov/29801011/ Perlis et. al.] Eur Urol. 2013 Sep;64(3):421-30.
+** '''Mechanism of action'''
+*** '''The two primary theories for recurrent tumor formation:'''
+**** '''Genetic field defect exists with multiple new tumors spontaneously arising within the bladder'''
+**** '''Local reimplantation of tumor cells after tumor resection'''
+***** '''Tumor cell implantation immediately after resection may be responsible for many early recurrences, and this has been used to explain the observation that initial tumors are most commonly found on the floor and lower sidewalls of the bladder, whereas recurrences are often located near the dome as a result of “flotation”'''
+***** '''Immediate instillation of intravesical chemotherapy may reducing tumor cell implantation'''
+*** '''Intravesical chemotherapy may also have an ablative effect on small occult tumours'''
+*'''<span style="color:#ff0000">Commonly used intravesical agents for single post-operative intravesical instillation of chemotherapy (5):</span>'''
 *# '''<span style="color:#ff0000">Gemcitabine</span>''' (SWOG S0337[https://pubmed.ncbi.nlm.nih.gov/29801011/ §])
+*##Mechanism of action: inhibits DNA synthesis
+*##Dose: 2g in 100mL[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5315602/]
 *# '''<span style="color:#ff0000">Mitomycin C (MMC)</span>'''
+*##Mechanism of action: alkylating agent that inhibits DNA replication
+*##Dose: 40g in 20-40mL
 *# '''<span style="color:#ff0000">Doxorubicin</span>'''
 *# '''<span style="color:#ff0000">Epirubicin</span>'''
@@ Line 92: / Line 126: @@
 *** As per 11th Ed. Campbell’s, MMC appears to be the most effective adjuvant intravesical chemotherapeutic agent perioperatively, although epirubicin is used in Europe and direct comparative studies are lacking).
 ** '''Thiotepa has also been evaluated'''
-* '''<span style="color:#ff0000">Reduces risk of tumour recurrence (absolute risk reduction ≈12%);</span> <span style="color:#ff0000">no benefit of chemotherapy on progression</span>'''
-** '''BCG is the only agent shown to delay or reduce high-grade tumor progression.''' No chemotherapy trials have achieved a significant reduction in progression
-** '''<span style="color:#ff00ff">Meta-analysis evaluating intravesical chemotherapy on risk of recurrence</span>'''
-*** 13 studies including 2548 patients
-*** '''<span style="color:#ff0000">Intravesical chemotherapy</span>''' prolonged recurrence-free interval by 38% (HR: 0.62; 95% confidence interval [CI], 0.50-0.77; p<0.001; I(2): 69%), '''<span style="color:#ff0000">and early recurrences were 12% less likely in the intervention population (ARR: 0.12'''</span>; 95% CI, -0.18 to -0.06; p<0.001, I(2): 0%). '''The number needed to treat to prevent one early recurrences was 8''' (95% CI, 6-17 patients).
-*** High risk of bias present in 12 of 13 publications. Quality of evidence for recurrence-free interval was very low and low for early recurrences.
-*** Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. [https://pubmed.ncbi.nlm.nih.gov/29801011/ Perlis et. al.] Eur Urol. 2013 Sep;64(3):421-30.
-* '''Mechanism of action'''
-** '''The two primary theories for recurrent tumor formation:'''
-*** '''Genetic field defect exists with multiple new tumors spontaneously arising within the bladder'''
-*** '''Local reimplantation of tumor cells after tumor resection'''
-**** '''Tumor cell implantation immediately after resection may be responsible for many early recurrences, and this has been used to explain the observation that initial tumors are most commonly found on the floor and lower sidewalls of the bladder, whereas recurrences are often located near the dome as a result of “flotation”'''
-**** '''Immediate instillation of intravesical chemotherapy may reducing tumor cell implantation'''
-** '''Intravesical chemotherapy may also have an ablative effect on small occult tumours'''
-* '''<span style="color:#ff0000">Particularly effective for the initial presentation of a (3):</span>'''
-*# '''<span style="color:#ff0000">Solitary</span>'''
-*# '''<span style="color:#ff0000">Low-grade</span>'''
-*# '''<span style="color:#ff0000">Papillary tumor</span>'''
-** '''<span style="color:#ff0000">The incremental benefit in patients with recurrent or multiple tumors is limited.</span>'''
-** '''<span style="color:#ff0000">No benefit has been found in patients with high-grade disease.</span>'''
-** '''Given the number needed to treat of 8, some authors have suggested that intravesical chemotherapy reduces overall cost of care by reducing the need for secondary resections. However, subsequent studies have shown that the tumors prevented are primarily smaller tumors that are often treated in the office or ambulatory surgery setting so the economic impact regarding recurrences remains controversial if recurrences are treated in any manner other than inpatient care'''
-* '''<span style="color:#ff0000">Indications</span>'''
-** <span style="color:#ff0000">'''See'''</span> '''[[CUA/AUA: Non-muscle Invasive Bladder Cancer (2021 CUA/2016 AUA))|2016 AUA/2021 CUA NMBIC]] <span style="color:#ff0000">Guideline Notes</span>'''
-* '''Contraindications'''
-*# '''After extensive resection'''
-*# '''Bladder perforation is suspected'''
-*# '''Significant bleeding'''
-*#*'''Saline irrigation might be a consideration for patients with low- and intermediate risk NMIBC post-TURBT when intravesical chemotherapy is contraindicated (e.g., extensive bladder resection) or unavailable (2021 CUA NMIBC Guidelines)'''
 *'''<span style="color:#ff0000">Steps for Successful Perioperative Administration of Intravesical Chemotherapy</span>'''
 *# '''Include intent to administer perioperative chemotherapy (and agent) on actual operative schedule.'''
@@ Line 145: / Line 151: @@
 *** '''<span style="color:#ff0000">Calcified eschars</span>'''
 *** '''<span style="color:#ff0000">Added difficulty of subsequent cystectomy</span>'''
-*** '''Serious sequelae and rare deaths have occurred, especially in patients with perforation during resection. <span style="color:#ff0000">Chemotherapy should be withheld in patients with extensive resection or when there is concern about perforation.</span>'''
+*** '''Serious sequelae and rare deaths have occurred, especially in patients with perforation during resection.'''
+****'''<span style="color:#ff0000">Chemotherapy should be withheld in patients with extensive resection or when there is concern about perforation.</span>'''
+***'''Given side effects of MMC, consider preferential use of gemcitabine which is better tolerated'''
 ** '''<span style="color:#ff0000">Thiotepa</span>'''
 *** '''<span style="color:#ff0000">Local irritative symptoms</span>'''