Editing CUA: Muscle-invasive Bladder Cancer (2019) (section)

=== Chemotherapy ===
* '''Neoadjuvant chemotherapy (NAC)'''
** '''All eligible patients with cT2-T4a N0 M0 urothelial carcinoma of the bladder should be encouraged to receive cisplatin-based combination chemotherapy as NAC prior to radical local therapy'''
*** Note that Grossman/SWOG trial was of patients with cT2-T4a N0 M0 urothelial carcinoma of the bladder
*** '''The role of NAC in pure non-urothelial carcinoma (squamous cell carcinoma, adenocarcinoma, etc.) is not defined and should not be utilized'''
**** '''Campbell’s: Exception, NAC is standard for pure neuroendocrine and small cell bladder carcinoma'''
** '''NAC Regimen Options (3):'''
*** '''Gemcitabine/Cisplatin (GC)'''
*** '''MVAC'''
*** '''dd-MVAC'''
** '''Contraindications to cisplatin-based NAC'''
*** '''Absolute (6, first 4 same as AUA):HE 2 NICE'''
**** '''≥Grade 2 Hearing loss''' (grading based on Common Terminology Criteria for Adverse Events version 4.0)
**** '''eGFR ≤ 50''' ml/min/1.73m2
***** To optimize renal function in patients considering and/or eligible for NAC, malignant ureteric obstruction should be relieved via percutaneous drainage nephrostomy tubes
**** '''≥Grade 2 Neuropathy''' (grading based on Common Terminology Criteria for Adverse Events version 4.0)
**** '''Untreated Infection'''
**** '''Cardiac failure (NYHA Class > 2)'''
**** '''Eastern Cooperative Group (ECOG)≥2'''
*** '''Relative (2):'''
**** '''eGFR between 50-60 ml/min/1.73m2'''
**** '''History of recurrent infection and concomitant immunosuppression'''
*** '''Patients with contraindications to cisplatin-based NAC should proceed directly to radical local therapy''' i.e. there is no second-line regimen for NAC
** '''After 2/4 cycles of GC or conventional MVAC NAC, restaging should be performed to ensure treatment response or stable disease during chemotherapy.'''
*** '''In the event of non-metastatic progressive disease or significant toxicity to chemotherapy that precludes its delivery, NAC should be discontinued and cystectomy performed within 4-6 weeks of last chemotherapy'''.
*** '''Patients receiving ddMVAC, given every 2 weeks, do not need restaging''' in the midst of chemotherapy as the short course of treatment precludes the need for imaging
* '''Adjuvant chemotherapy'''
** '''In patients who do not receive NAC prior to cystectomy, adjuvant cisplatin-based combination chemotherapy (GC, MVAC or dd-MVAC) should be offered to those eligible patients with:'''
**# '''pT3/T4 and/or'''
**# '''N+ disease'''
* '''Unresectable disease'''
** '''See 2019 CUA Consensus Statement on locally advanced and metastatic urothelial carcinoma'''
** Patients with non-metastatic, clinically unresectable, cT4b or cN+ tumours should be offered induction (primary) cisplatin-based combination chemotherapy with either GC, MVAC or ddMVAC if eligible, or an alternative combination chemotherapy regimen if platinum-ineligible (e.g. Gemcitabine/Carboplatin), single-agent chemotherapy or enrolment in a clinical trial, if available