Non-Muscle Invasive Bladder Cancer: Difference between revisions
Urology4all (talk | contribs) No edit summary |
Urology4all (talk | contribs) |
||
| Line 414: | Line 414: | ||
=== '''Management options in BCG unresponsive disease''' === | === '''Management options in BCG unresponsive disease''' === | ||
* '''See 2016 AUA/2021 CUA NMBIC Guideline Notes''' | * '''<span style="color:#ff0000">See</span> 2016 <span style="color:#ff0000">AUA/2021 CUA NMBIC Guideline Notes</span>''' | ||
* '''Standard of care: radical cystectomy + lymph node dissection''' | * '''<span style="color:#ff0000">Standard of care: radical cystectomy + lymph node dissection''' | ||
** '''BCG-unresponsive with CIS or HG Ta: a second-line intravesical therapy might be considered before radical cystectomy''' | ** '''<span style="color:#ff0000">BCG-unresponsive with CIS or HG Ta: a second-line intravesical therapy might be considered before radical cystectomy''' | ||
* '''BCG-unresponsive with CIS who are unfit for or refuse to undergo radical cystectomy (4):''' | * '''<span style="color:#ff0000">BCG-unresponsive with CIS who are unfit for or refuse to undergo radical cystectomy (4):''' | ||
*# '''Intravenous pembrolizumab''' | *# '''<span style="color:#ff0000">Intravenous pembrolizumab''' | ||
*# '''Intravesical oportuzumab monatox''' | *# '''<span style="color:#ff0000">Intravesical oportuzumab monatox''' | ||
*# '''Intravesical nadofaragene firadenovec''' | *# '''<span style="color:#ff0000">Intravesical nadofaragene firadenovec''' | ||
*# '''BCG plus N-803''' | *# '''<span style="color:#ff0000">BCG plus N-803''' | ||
** Chemoradiation should not be recommended for patients with BCG-unresponsive CIS | ** Chemoradiation should not be recommended for patients with BCG-unresponsive CIS | ||
* '''BCG-unresponsive who are unfit for or refuse to undergo radical cystectomy''' | * '''<span style="color:#ff0000">BCG-unresponsive who are unfit for or refuse to undergo radical cystectomy''' | ||
*# '''Clinical trial''' | *# '''<span style="color:#ff0000">Clinical trial''' | ||
*# '''Sequential intravesical gemcitabine/docetaxel§ (induction plus maintenance)''' | *# '''<span style="color:#ff0000">Sequential intravesical gemcitabine/docetaxel§ (induction plus maintenance)''' | ||
*# '''Other combination intravesical therapy (e.g., sequential gemcitabine/MMC, BCG + interferon if available)''' | *# '''<span style="color:#ff0000">Other combination intravesical therapy (e.g., sequential gemcitabine/MMC, BCG + interferon if available)''' | ||
*# '''Single-agent intravesical therapy (MMC, epirubicin, docetaxel, gemcitabine)''' | *# '''<span style="color:#ff0000">Single-agent intravesical therapy (MMC, epirubicin, docetaxel, gemcitabine)''' | ||
*#* '''For BCG-unresponsive patients undergoing intravesical chemotherapy, sequential combination of drugs is favoured instead of single-agent regimens''' | *#* '''For BCG-unresponsive patients undergoing intravesical chemotherapy, sequential combination of drugs is favoured instead of single-agent regimens''' | ||
*#* '''See Table 5 from 2021 CUA NMIBC Guidelines for dosing''' | *#* '''See Table 5 from 2021 CUA NMIBC Guidelines for dosing''' | ||
*# '''Repeat induction BCG''' | *# '''<span style="color:#ff0000">Repeat induction BCG''' | ||
*#* '''In patients with NMIBC treated with an induction course of BCG (without maintenance) who later develop recurrence of disease (BCG relapse), a second induction course may achieve 30-50% response rates.''' | *#* '''In patients with NMIBC treated with an induction course of BCG (without maintenance) who later develop recurrence of disease (BCG relapse), a second induction course may achieve 30-50% response rates.''' | ||
*#** '''>2 BCG induction courses is not recommended due to high failure rate''' | *#** '''>2 BCG induction courses is not recommended due to high failure rate''' | ||
<br> | <br> | ||
* '''Pembrolizumab''' | * '''<span style="color:#ff0000">Pembrolizumab''' | ||
** '''Systemic immunotherapy for NMIBC''' | ** '''Systemic immunotherapy for NMIBC''' | ||
** '''MOA: PD-1 checkpoint inhibitor''' | ** '''MOA: PD-1 checkpoint inhibitor''' | ||
** '''Dose: 200 mg IV q3weeks for up to 24 months''' | ** '''Dose: 200 mg IV q3weeks for up to 24 months''' | ||
** '''KEYNOTE-057''' | ** '''<span style="color:#ff00ff">KEYNOTE-057''' | ||
*** '''Population: 96 patients with BCG-unresponsive CIS''' | *** '''Population: 96 patients with BCG-unresponsive CIS''' | ||
*** '''Single arm study: 200 mg of pembrolizumab IV q3 weeks for 24 months or until recurrence, progression or limiting toxicity''' | *** '''Single arm study: 200 mg of pembrolizumab IV q3 weeks for 24 months or until recurrence, progression or limiting toxicity''' | ||
| Line 448: | Line 448: | ||
**** '''Adverse events: pneumonitis (3%), colitis (2%)''' | **** '''Adverse events: pneumonitis (3%), colitis (2%)''' | ||
*** '''Balar, Arjun V., et al."Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study." ''The Lancet Oncology'' (2021).''' | *** '''Balar, Arjun V., et al."Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study." ''The Lancet Oncology'' (2021).''' | ||
* '''Nadofaragene firadenovec (Adstiladrin)''' | * '''<span style="color:#ff0000">Nadofaragene firadenovec (Adstiladrin)</span>''' | ||
** '''MOA: a non-replicating adenovirus vector (rAd-INFa/Syn3) together with recombinant IFN-alpha2b. When given intravesically, the virus is transduced into bladder cells and the IFN-alpha2b gene is incorporated by the DNA. IFNalpha2b protein, which has antitumour activity, is then produced.''' | ** '''MOA: a non-replicating adenovirus vector (rAd-INFa/Syn3) together with recombinant IFN-alpha2b. When given intravesically, the virus is transduced into bladder cells and the IFN-alpha2b gene is incorporated by the DNA. IFNalpha2b protein, which has antitumour activity, is then produced.''' | ||
*** '''Single-arm trial''' | *** '''<span style="color:#ff00ff">Single-arm trial</span>''' | ||
*** '''Population: 157 patients with BCG-unresponsive non-muscle-invasive bladder cancer''' | *** '''Population: 157 patients with BCG-unresponsive non-muscle-invasive bladder cancer''' | ||
*** '''Results:''' | *** '''Results:''' | ||
**** '''53% of patients with (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 46% of 55 patients at 12 months.''' | **** '''53% of patients with (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 46% of 55 patients at 12 months.''' | ||
*** '''Boorjian, Stephen A., et al."Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial." ''The Lancet Oncology'' 22.1 (2021): 107-117.''' | *** '''Boorjian, Stephen A., et al. "Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial." ''The Lancet Oncology'' 22.1 (2021): 107-117.''' | ||
* '''Oportuzumab monatox (Vicineum)''' | * '''Oportuzumab monatox (Vicineum)''' | ||
** '''MOA: specific antibody to Epithelial Cell Adhesion Molecule (EpCAM) fused to a Pseudomonas toxin that binds specifically to bladder cancer cells.''' | ** '''MOA: specific antibody to Epithelial Cell Adhesion Molecule (EpCAM) fused to a Pseudomonas toxin that binds specifically to bladder cancer cells.''' | ||