Outcomes of squamous histology in bladder cancer: a population-based study.
Squamous cell carcinoma (SCC) of the bladder is an uncommon form of bladder cancer. Using a large population-based sample we sought to describe the outcomes of patients with squamous histology and to define the factors that influence prognosis in these patients.
All incident cases of bladder cancer in Ontario undergoing cystectomy from 1994 to 2008 were identified. Electronic treatment records and detailed pathologic information were linked to the study data set. Patients were divided into 3 cohorts: pure SCC, urothelial carcinoma (UC) with squamous differentiation (UCSD), and pure UC. Cox modeling was performed to evaluate factors associated with overall survival (OS) and cancer-specific survival (CSS).
There were identified 178, 325, and 2,884 cases of SCC, UCSD, and UC, respectively. The unadjusted 5-year OS for these groups were 33%, 28%, and 34%, respectively. Patients had higher rates of T3/4 disease with SCC (72%) and UCSD (73%) than those with UC (61%, P<0.001). There was no difference in node positivity among groups (20%, 27%, and 25%, P = 0.519). After adjusting for covariates, SCC did not portend a worse survival, at 5 years. However, SCC did result in a more rapid disease trajectory, with survival curves of SCC and UC crossing at the 5-year mark. Adjusted CSS/OS of UCSD was also not significantly different from UC. Among those patients with SCC, factors associated with CSS included age>70 (hazard ratio [HR] = 1.96, 95% CI: 1.16-3.30), T category≥3 (HR = 2.09, 95% CI: 1.24-3.50), N positive disease (HR = 2.59, 95% CI: 1.55-4.32), lymphovascular invasion (HR = 1.98, 95% CI: 1.13-3.47), and positive surgical margins (HR = 2.95, 95% CI: 1.47-5.93).
After adjusting for patient and disease characteristics, we have found that SCC leads to a more rapid disease course with survival that is equivalent to UC by 5 years.
Izard JP
，Siemens DR
，Mackillop WJ
，Wei X
，Leveridge MJ
，Berman DM
，Peng Y
，Booth CM
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Expression and prognostic utility of PD-L1 in patients with squamous cell carcinoma of the bladder.
Checkpoint inhibitors are approved for the treatment of urothelial bladder cancer. However, there have been no reports on the prognostic value of programmed-death receptor ligand 1 (PD-L1) expression in squamous cell carcinoma (SCC) of the bladder. We assessed the relationship between PD-L1 expression, clinicopathological features, and oncologic outcomes in bladder SCC.
Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated in Mansoura, Egypt from 1997 to 2004.
Median patient age was 52 years (range: 36-74 years) and median length of follow up was 63 months (range: 1-100 months). Schistosomiasis was present in 81% of the specimens and 93% had muscle-invasive disease on pathologic staging. PD-L1 expression was negative in 50 (33%) of the specimens. Negative PD-L1 expression was associated with higher pathologic tumor stage (P = 0.04), higher grade lesions (P = 0.01), and the presence of lymphovascular invasion (P < 0.01). Kaplan-Meier analyses showed that negative PD-L1 expression is associated with worse recurrence-free (P = 0.01) and worse cancer-specific survival (P = 0.01). Multivariable Cox regression analyses showed negative PD-L1 expression was an independent predictor of disease recurrence (hazards ratio 2.05, 95% confidence interval 1.06-3.96, P = 0.03) and cancer-specific mortality (hazards ratio 2.89, 95% confidence interval 1.22-6.82, P = 0.02).
Negative PD-L1 expression is associated with higher pathologic tumor stage, higher grade lesions, presence of lymphovascular invasion, and worse oncologic outcomes after radical cystectomy for SCC. These findings support the need for the inclusion of patients with bladder SCC into immunotherapy clinical trials.
Owyong M
，Lotan Y
，Kapur P
，Panwar V
，McKenzie T
，Lee TK
，Zi X
，Martin JW
，Mosbah A
，Abol-Enein H
，Ghoneim M
，Youssef RF
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Prognostic value of pretreatment inflammatory markers in variant histologies of the bladder: is inflammation linked to survival after radical cystectomy?
To investigate differences in standard preoperative inflammatory markers in patients with urothelial carcinoma (UC) and variant histologies undergoing radical cystectomy (RC) and determine its impact on survival.
Patients undergoing RC at an academic high-volume center were retrospectively analyzed. Preoperatively taken CRP, leukocytes, hemoglobin (Hb), and thrombocytes were analyzed as routine inflammatory biomarkers. Log-rank tests and Kruskal-Wallis analysis were used to calculate for differences in survival and in blood levels of biomarkers.
886 patients with complete follow-up and UC or variant histology underwent RC at our institution between 2004 and 2019. Although variant histology presents with significantly higher t stage than UC, cancer-specific survival (CSS) of UC (1-year-CSS: 93%) is not significantly different to variant histology of UC with squamous differentiation (UCSD, 1-year-CSS: 81%), squamous cell carcinoma (SCC, 1-year-CSS: 82%), and adenocarcinoma (AC, 1-year-CSS: 81%). In UC, alterations in all biomarkers except leukocytes beyond routine cut-off values were associated with poor survival (p < 0.01), whereas Hb beyond cut-off values are associated with poor prognosis in SCC (p < 0.05). CRP levels are significantly elevated in UCSD and SCC at time of surgery compared to UC (p < 0.05).
Inflammatory biomarkers reveal distinctive patterns across UC and variant histologies of bladder cancer. As inflammation might play an important role in cancer progression, further research is warranted to understand those molecular mechanisms and their potential therapeutic impact in variant histology of bladder cancer.
Rodler S
，Buchner A
，Ledderose ST
，Eismann L
，Volz Y
，Pfitzinger P
，Kretschmer A
，Schulz GB
，Karl A
，Schlenker B
，Stief CG
，Jokisch F
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