Editing Muscle-Invasive Bladder Cancer (section)

===== <span style="color:#ff0000">Timing of radical cystectomy after NAC</span> =====
*'''<span style="color:#ff0000">Radical cystectomy is recommended as soon as possible following completion of and recovery from NAC, ideally within 12 weeks (CUA: 4-6 weeks after NAC and no more than 10 weeks), following completion of chemotherapy</span>''', unless medically inadvisable.
**Patients must be medically fit to undergo cystectomy.
**Optimal timing to proceed with cystectomy after chemotherapy has not been defined.
***Observational studies that suggest that outcomes may be worse if cystectomy is delayed more than 12 weeks after the completion of chemotherapy.
====== Adverse events ======

* '''Cisplatin eligibility is a major determinant of candidacy for NAC'''

* '''<span style="color:#ff0000">Adverse events related to cisplatin (4):</span>'''
*# '''<span style="color:#ff0000">Nephrotoxicity</span>'''
*# '''<span style="color:#ff0000">Ototoxicity</span>'''
*# '''<span style="color:#ff0000">Neurotoxicity</span>'''
*# '''<span style="color:#ff0000">Diminished cardiac function</span>'''
** '''These preclude 30-50% of MIBC patients from safe receipt of cisplatin-based chemotherapy'''
* '''No validated predictive factors or clinical characteristics (including age) associated with an increased or decreased probability of response and benefit using cisplatin-based NAC'''
** The decision regarding eligibility for cisplatin-based NAC should be based on comorbidities and performance status, including cardiac status and presence of peripheral neuropathy, hearing loss, and renal dysfunction

====== Histological considerations ======
* '''<span style="color:#ff0000">NAC is primarily derived in the urothelial carcinoma setting</span>'''
** '''Secondary analysis of SWOG 8710 found that patients with mixed tumours (squamous and glandular differentiation) derived greater benefit''' (HR 0.46) '''from neoadjuvant MVAC than patients with pure urothelial carcinoma''' (HR 0.9), compared with cystectomy[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117124/ §]
* '''<span style="color:#ff0000">Lack of robust data supporting NAC in pure non-urothelial histologies</span>'''
** '''Exceptions are pure small cell or pure neuroendocrine carcinoma of the bladder where NAC is the mainstay of treatment'''
** '''[CUA Guidelines do not support NAC in pure non-urothelial histology, other than noted exceptions]'''