Editing Non-Urothelial Bladder Cancer (section)

===Management===
*No proven role for neoadjuvant/adjuvant chemotherapy for pure squamous cell carcinoma of the bladder. [2022 NCCN Guidelines]
*Pure squamous cell tumors are treated by cystectomy, RT, or agents commonly used for squamous cell carcinoma of other sites such as 5-FU or taxanes. [2022 NCCN Guidelines]
*No significant difference in survival among cystectomy patients found to have pure squamous cell carcinoma vs. urothelial carcinoma with squamous differentiation.[https://pubmed.ncbi.nlm.nih.gov/22088332/]
*'''If T1 squamous bladder cancer without pure squamous cell carcinoma or lymphovascular invasion at initial TURB specimen, consider intravesical BCG. Else, consider immediate RC with pure squamous cell carcinoma or lymphovascular invasion.'''
**'''Retrospective, multi-center''' (15 centers) '''cohort study of 188 patients with T1 HG squamous bladder cancer (pure or urothelial carcinoma with squamous differentiation) managed with immediate radical cystectomy (RC) vs. BCG immunotherapy''' between 1998-2019.
***Immediate RC consisted of RC with bilateral pelvic lymph node dissection performed within 3 months from diagnosis, some preceded by re-TURB.
***BCG immunotherapy, some preceded by re-TURB, included at least 6 induction instillations and eventually maintenance course.
****When performed, re-TURB consisted of second look performed within 6 weeks from initial diagnosis; patients who underwent re-TURB were subsequently referred to immediate RC or BCG according to the second pathological report, patient’s and surgeon’s discretion.
***'''Diagnosis of squamous bladder cancer was assigned if ANY squamous component was found on the pathological report regardless of the percentage, including both pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation'''
**'''Primary outcomes: cancer-specific and overall survival'''
**'''Results'''
***Pure squamous cell carcinoma was found in 30% (n=57) of patients, while 19% (n=36), 5% (n=9), and 46% (n=86) of individuals showed UC with focal, extensive, or unknown squamous differentiation, respectively.
***Primary treatment: immediate RC in 20% (n=37) vs. BCG immunotherapy in 80%(n=151)
***Median follow-up was 36 months (IQR: 19–76); overall, 53 patients (28%) died from any cause and 34 patients (18%) from bladder cancer.
***Primary outcomes among all patients with squamous bladder cancer (pure squamous cell carcinoma and urothelial carcinoma with any extent of squamous differentiation):
****5-year cancer-specific mortality: no significant difference (29% immediate RC vs. BCG immunotherapy 16%)
****5-year overall mortality: no significant difference (34% immediate RC vs. BCG immunotherapy 26%)
***'''In patients receiving BCG'''
****'''Pure squamous cell carcinoma was associated with a significantly increased risk of tumour progression (hazard ratio [HR]: 2.40; ''p'' = 0.04)'''
****Lymphovascular invasion was associated with a significantly increased risk of tumour recurrence and progression
**[https://pubmed.ncbi.nlm.nih.gov/35218372/ Lonati, Chiara, et al.] "Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration." ''World Journal of Urology'' 40.5 (2022): 1167-1174.