Table 6. Studies on glandular/squamous differentiation reporting outcomes with either neoadjuvant chemotherapy or upfront radical cystectomy.
| Author (year) | Pathologic complete response | Pathologic downstaging | Median follow up after cystectomy | Survival outcomes after cystectomy | Major independent factor(s) other than histologic phenotype affecting response/outcomes analyzed | Comments |
|---|---|---|---|---|---|---|
| Speir (6) (2021), n=71 (VH n=71) | NAC resulted in 12.4 times higher likelihood to achieve pCR, more than seen in patients who did not receive NAC [60% vs. 10.8%; odds ratio (OR), 12.4; 95% confidence interval (CI), 3.15–48.7; P<0.001] | 38.2 months | Comparing patients who received NAC and those who did not, there was improved OS, DSS and RFS in patients receiving NAC | % squamous differentiation was used to group patients into two categories (<50% vs. ≥50%), probability of pCR was higher in patients with % squamous differentiation <50% (26.7 vs. 8.7) and benefit in OS and RFS with NAC was lost when % SV was ≥50 | ||
| MIBC patients having Squamous differentiation who had Radical Cystectomy | ||||||
| Buisan (9) (2017), n=50 (VH n=50) | 29 months | Neutrophil-to-lymphocyte (NLR) ratio in squamous differentiation was predictive of positive response to NAC. NAC was of significant benefit in patients with NLR<5. CSS was 91.2 months vs. 38.1 months for those treated with upfront RC (P=0.009). There was no statistically significant difference in survival for patients with NLR ≥5 | Aim of this study was to determine impact of neutrophil-to-lymphocyte (NLR) ratio on treatment outcomes. Patients were stratified into two groups, 1. NLR <5; 2. NLR ≥5 | |||
| MIBC patients having squamous differentiation. 19 patients were treated with NAC | ||||||
| Zargar-Shoshtari (13) (2016), n=126 (VH n=20) | Comparing two patient groups receiving NAC - UC with divergent glandular or squamous differentiation vs. conventional UC, pCR were similar between the groups (25% vs. 21%; P=0.07) | Comparing two patient groups receiving NAC – UC with divergent differentiation vs. conventional UC, rates of pathological downstaging were significantly higher in divergent glandular or squamous differentiation subgroup receiving NAC (60 vs. 32%; P=0.02) | Only clinical stage was predictive of pathologic response to NAC | Divergent glandular or squamous differentiation were independent predictors of pathologic downstaging [odds ratio (OR), 4.01; 95% confidence interval (CI), 1.16-13.9] and clinical stage (OR, 2.91; 95% CI, 1.06-7.94) in a multivariable logistics regression model | ||
| Kim (29) (2012), n=1,023 (VH n=186) | 11.4 years | Comparing survival outcomes between UC with divergent squamous or glandular differentiation with conventional UC, 10-year CSS did not differ significantly between the two groups (52% vs. 51%; P=0.71) | Pathological stage, lymph node status and lymphovascular invasion were associated with an increased risk of mortality | UC with divergent squamous or glandular differentiation was not significantly associated with risk of death from bladder cancer after adjusting for clinicopathologic features (HR 0.79, P=0.10) | ||
| Antunes (30) (2007), n=133 (VH n=25) | 24 months | Comparing patients with tumors having squamous differentiation to those who did not, disease recurrence occurred in 64% vs. 34% (P=0.001), and death occurred in 40% vs. 16% of patients (P=0.002) | Univariate analysis revealed that pathological T stage, tumor size and lymph node involvement were predictors of CSS. Only tumor size was an independent predictor of outcome on multivariable analysis | |||
| Ehdie (31) (2012), n=145 (VH n=67) | 44 months | There was no statistically significant difference in survival outcomes between SCC and UC with squamous differentiation in terms of CSS and OS | Patients with squamous differentiation with lymph node involvement had worse OS and CSS | The aim of the study was to compare outcomes and determine predictors of CSS and OS between SCC cases and UC with squamous differentiation cases after RC | ||
| Minato (33) (2018), n=101 (VH n=20) | 31 months | Comparing UC with squamous differentiation and conventional UC, five-year OS and RFS rates were 41.1% vs. 69.7 % (P=0.002) and 51.8% vs. 59.5% (P=0.027) respectively | Percentage/extent of squamous differentiation had no effect on survival outcomes | Squamous differentiation was a significant independent predictor of OS on multivariate analysis (HR: 4.22; 95% CI: 1.20–14.8; P=0.024) |
UC, urothelial carcinoma; VH, variant histology; NAC, neoadjuvant chemotherapy; MIBC, muscle invasive bladder cancer; pCR, pathologic complete response; RFS, recurrence free survival; CSS, cancer specific survival; OS, overall survival; DSS, disease specific survival; NLR, neutrophil-lymphocyte ratio; OR, odds ratio; SCC, squamous cell carcinoma.