The Impact of Histological Variants on Oncological Outcomes in Patients with Muscle Invasive Bladder Cancer Treated with Radical Cystectomy.

OBJECTIVE: Bladder cancer is a heterogeneous entity characterized by a wide range of different morphologies. The aim of this study was to investigate the prognostic effect of bladder tumor with variant histology that is treated with radical cystectomy on oncological outcomes. METHODS: One hundred eighty-six patients who underwent radical cystectomy between September 2001 and June 2020 were included in the study. The patients were divided into 2 groups variant histology group (n = 54) and transitional cell cancer group (n = 132). Clinicopathologic data were compared between the two groups. RESULTS: The groups were similar in terms of demographic characteristics. In the mul- tivariate analysis of cancer-specific survival in transitional cell cancer against variant histology, high-grade detection of primary transurethral bladder tumor pathology, cystectomy pT, cystectomy positive lymph node, and positive surgical margin in cys- tectomy were determined to be statistically significant. Diagnosis of pT2 and high grade of primary transurethral bladder tumor pathology, cystectomy ≥ pT3, cystec- tomy positive lymph node, and positive surgical margin in cystectomy were statis- tically significant in multivariate analysis of overall survival. Cancer-specific survival time was estimated at 65.1 ± 8.3 months for variant histology and 134.2 ± 10.4 months for transitional cell cancer (P=.004). The estimated overall survival time was 61.9 ± 8.0 months in variant histology and 119.0 ± 9.8 months in transitional cell cancer (P = .014). CONCLUSION: Pathological features and prognosis of bladder cancer with variant histol- ogies are worse than those of pure urothelial bladder cancer. Overall survival and can- cer-specific survival are shorter in bladder cancer with variant histology than in pure urothelial bladder cancer. Following the diagnosis of variant histology in transurethral bladder tumor, poor prognosis must be considered in the treatment plan.

Clinicopathologic features and prognostic significance of mixed (Low and high-grade) papillary urothelial carcinoma comparison with low and high-grade papillary urothelial carcinoma.

The World Health Organization/International Society of Urological Pathology (2022 WHO/ISUP) classification categorizes noninvasive carcinomas based on the highest grade observed in a pathology sample. According to this classification, a lesion is classified as mixed-grade (MG) if the highest-grade component comprises less than 5% high-grade (HG) carcinoma [14]. This study included 160 cases of low-grade papillary urothelial carcinoma (LGUC) and 160 cases of HG papillary urothelial carcinoma (HGUC), selected randomly. In addition, 160 consecutive and unselected cases of MG papillary urothelial carcinoma (MGUC) were obtained from all bladder transurethral resection specimens diagnosed with papillary urothelial carcinoma between January 2007 and January 2021. The results of the multivariate analysis showed that histologic grade, invasion of the lamina propria, and the presence of carcinoma in situ at presentation were independent prognostic parameters regarding recurrence-free survival (p = 0.002; hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.059-1.956, p = 0.02; and HR = 1.76, 95% CI = 1.159-2.684, p = 0.008, respectively). Histologic grade was the only independent prognostic parameter of disease-specific survival (DSS) (p < 0.001). Comparisons between non-muscle invasive (NMI) MGUC and NMI LGUC, as well as between NMI MGUC and NMI HGUC, revealed statistically significant differences in terms of DSS (HR = 0.07, 95% CI = 0.024-0.252, p < 0.001 and HR = 1.59, 95% CI = 1.023-2.460, p = 0.039, respectively). Our study findings demonstrate statistically significant differences regarding DSS between NMI MGUC and NMI HGUC, as well as between NMI MGUC and NMI LGUC. Therefore, we suggested that considering the presence of less than 5% MGUC as a separate category may be appropriate. However, it is important to validate our results in larger cohorts with longer follow-up periods to establish the clinical significance of MGUC and provide guidance for patient management.

The prognostic impact of tumor necrosis in non-muscle invasive bladder cancer.

OBJECTIVE: We aimed to investigate the impact of tumor necrosis in non-muscle invasive bladder cancer on patients' recurrence and progression rates and survival outcomes. METHODS: This study was conducted retrospectively in a single tertiary center in Turkey. Medical records of patients who underwent transurethral resection of the bladder tumor between January 2016 and January 2021 were reviewed. Patients with pTa and pT1 non-muscle invasive bladder cancer who had undergone complete resection were included in our study. All pathological specimens were reevaluated for the presence of tumor necrosis. RESULTS: A total of 287 patients (244 males and 43 females) were included in our study. Of them, 33 (11.5%) patients had tumor necrosis. The rates of multiple and large tumors (>3 cm) were higher in patients with tumor necrosis (p=0.002 and p<0.001, respectively). Tumor necrosis was associated with higher rates of pT1 diseases (p<0.001), high-grade tumors (p<0.001), and the presence of lymphovascular invasion (p=0.007). The mean recurrence-free survival of patients with tumor necrosis was 42.3 (4.6) months, and the recurrence-free survival of patients without tumor necrosis was 43.5 (1.8) months (p=0.720). The mean progression-free survival of patients with tumor necrosis was 43.1 (4.6) months, and the progression-free survival of patients without tumor necrosis was 58.4 (0.9) months. In log-rank analysis, there was a statistically significant difference between patients with and without tumor necrosis in terms of progression-free survival (p<0.001). CONCLUSION: In this study, we demonstrated that patients with non-muscle invasive bladder cancer and tumor necrosis in pathological specimens have shorter progression-free survival and more adverse pathological features.

The prognostic impact of tumor necrosis in non-muscle invasive bladder cancer

SUMMARY OBJECTIVE: We aimed to investigate the impact of tumor necrosis in non-muscle invasive bladder cancer on patients' recurrence and progression rates and survival outcomes. METHODS: This study was conducted retrospectively in a single tertiary center in Turkey. Medical records of patients who underwent transurethral resection of the bladder tumor between January 2016 and January 2021 were reviewed. Patients with pTa and pT1 non-muscle invasive bladder cancer who had undergone complete resection were included in our study. All pathological specimens were reevaluated for the presence of tumor necrosis. RESULTS: A total of 287 patients (244 males and 43 females) were included in our study. Of them, 33 (11.5%) patients had tumor necrosis. The rates of multiple and large tumors (>3 cm) were higher in patients with tumor necrosis (p=0.002 and p<0.001, respectively). Tumor necrosis was associated with higher rates of pT1 diseases (p<0.001), high-grade tumors (p<0.001), and the presence of lymphovascular invasion (p=0.007). The mean recurrence-free survival of patients with tumor necrosis was 42.3 (4.6) months, and the recurrence-free survival of patients without tumor necrosis was 43.5 (1.8) months (p=0.720). The mean progression-free survival of patients with tumor necrosis was 43.1 (4.6) months, and the progression-free survival of patients without tumor necrosis was 58.4 (0.9) months. In log-rank analysis, there was a statistically significant difference between patients with and without tumor necrosis in terms of progression-free survival (p<0.001). CONCLUSION: In this study, we demonstrated that patients with non-muscle invasive bladder cancer and tumor necrosis in pathological specimens have shorter progression-free survival and more adverse pathological features.

The association between PI3K, JAK/STAT pathways with the PDL-1 expression in prostate cancer.

Programmed cell death protein-1/programmed death-ligand-1 (PD-1/PDL-1) signalling pathway has gained attention in prostate cancer. The relationship between pSTAT-1, pSTAT-3 expressions and PTEN loss with PDL-1 expression was assessed and the effects of the pathways on prostate cancer prognosis were evaluated. Patients who underwent radical prostatectomy between 2011 and 2017 were included in our study. Prostatectomy materials were evaluated using immunohistochemical staining of pSTAT-1, pSTAT-3, PTEN, and PDL-1. The relationship between PDL-1 and pSTAT-1, pSTAT-3 expressions and PTEN loss was evaluated. Additionally, factors affecting biochemical recurrence-free survival and clinical progression-free survival were analysed. Within100 patients, 9 of 11 patients with PDL-1 expression also had intermediate-high pSTAT-1 staining intensity, and those with PDL-1 expression had higher pSTAT-1 staining intensity than those without (81.9% vs. 56.2%, p = 0.014). In univariate analysis, pSTAT-1, pSTAT-3 and PDL-1 expressions had significant impact on biochemical recurrence-free and clinical progression-free survival. In multivariate analysis, pSTAT-1 staining intensity with radical prostatectomy ISUP grade in terms of biochemical recurrence-free survival and the pSTAT-1 H-score with radical prostatectomy ISUP grade in terms of clinical progression-free survival were independent risk factors. Moderate-high expression of pSTAT-1 was closely associated with PDL-1 expression, and pSTAT-1 was also a predictor of biochemical recurrence and clinical progression.

PTEN Loss and PD-L1 Expression of Different Histological Patterns of Prostate Cancer.

AIMS: Although several studies have evaluated PTEN loss in Prostatic Adenocarcinoma (PCa), PTEN loss correlation with different histological patterns only has a few studies. Although several studies have evaluated PD-L1 expression in PCa and its correlation with Gleason scores, as far as we know, there are no prior studies that have included a comparison between PD-L1 expression and histological patterns of PCa. This study aims to evaluate PTEN loss and PD-L1 expression by immunohistochemistry in different histological patterns of PCa. METHODS: The current study included consecutive 98 radical prostatectomy specimens with 151 foci with different Gleason Grade (GG) patterns. RESULTS: The highest frequency of PTEN loss was observed in GG4 cribriform and glomeruloid patterns (59.3%, p < 0.001). Combined score (CS) PD-L1 positivity was observed in fourteen patients (14.2%). Tumor cell (TC) and tumor-associated inflammatory cells (IC) PD-L1 positivity was observed in 10 (10.2%) and 7 (7.1%) patients. The highest frequency of PD-L1 expression was observed in the GG5 pattern, and between GG4 patterns, the irregular pattern had the highest PD-L1 positivity. CONCLUSIONS: In conclusion, in our cohort of consecutive unselected cases of prostatic carcinoma, we observed the highest PTEN loss rate in the GG4 cribriform and glomeruloid pattern and the highest PD-L1 expression rate in the GG5 and GG4 irregular patterns. These results may predict molecular differences between different histological patterns in PCa and may be used to inform a treatment decision. Future studies should investigate these differences between histological patterns of PCa to predict response to immunotherapy in larger cohorts.