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Abstract

Objectives

To assess the impact of histological variants on survival and response to treatment with pembrolizumab in patients with chemoresistant urothelial cancer (UC).

Materials and Methods

The medical records of 755 patients with advanced UC who received pembrolizumab were reviewed retrospectively. Patients were classified into pure UC (PUC) and each variant. Best overall response (BOR)　and overall survival (OS) were compared between the groups using a propensity score matching (PSM).

Results

Overall, 147 (19.5%) patients harbored any histological variant UC (VUC). After PSM, there were no significant differences in objective response rate (ORR, 24.5% vs 17.3%, p = 0.098) and disease control rate (DCR, 36.7% vs 30.2%, p = 0.195) when comparing patients with any VUC and PUC. Furthermore, any VUC, as compared with PUC, were associated with a similar risk of death (hazard ratio, 0.90; 95% confidence interval [CI], 0.68 to 1.20; p = 0.482). Squamous VUC, which was the most frequent variant in the cohort, had comparable ORR, DCR and OS as compared with PUC or non-squamous VUC. The patients with sarcomatoid VUC (n = 19) had significantly better ORR (36.8%, p = 0.031), DCR (52.6%, p = 0.032), and OS (HR 0.37; 95% CI 0.15 to 0.90; p = 0.023) compared to patients with PUC.

Conclusions

The presence of variant histology did not seem to affect BOR or OS after pembrolizumab administration in patients with chemoresistant UC. The patients with sarcomatoid UC achieved favorable responses and survival rates compared to PUC.

Abstract

Objectives

To investigate the role of cancer-associated fibroblasts (CAFs) in clear cell renal cell carcinoma (ccRCC) with respect to tumor aggressiveness, metastasis development and resistance to antiangiogenic therapy (VEGFR-tyrosine kinase inhibitors, VEGFR-TKI).

Methods

Our study involved tissue samples from three distinct and independent cohorts of patients with ccRCC. The presence of CAFs and tumor lymphangiogenesis was investigated respectively by transcriptional signatures and then correlated with tumor development and prognosis. The effect of these CAFs on tumor cell migration and VEGFR-TKI resistance was analyzed on co-cultures of ccRCC cells with CAFs.

Results

Results from our cohorts and from in silico investigations showed that VEGFR-TKI significantly increase the number of CAFs in tumors. In the same populations of ccRCC patients, the proportion of intra-tumoral CAFs correlated to shorter disease-free and overall survival. The presence of CAFs was also correlated with lymphangiogenesis and lymph node metastasis. CAFs increased the migration and decrease the VEGFR-TKI-dependent cytotoxic effect of tumor cells.

Conclusions

Our results showed that VEGFR-TKI promote the development of CAFs, and CAFs favor tumor aggressiveness, metastatic dissemination and resistance to treatment in ccRCC. CAFs could represent a new therapeutic target to fight resistance to treatment of ccRCC. Targeting CAF and immunotherapies combination are emerging as efficient treatments in many types of solid tumors. Our results highlight their relevance in ccRCCs.

Objectives

To describe the trend in the impact of lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH) on a global scale using the Global Burden of Disease (GBD) database.

Materials and Methods

Using the GBD database, worldwide data aggregated from registries and health systems from 1990 to 2017 were filtered for LUTS/BPH diagnoses. Calculation of years lived with disability (YLD) were compared with other urological diseases. YLD were calculated by a standardized method using assigned disability weights. The GBD-defined sociodemographic index (SDI) was used to assess impact of LUTS/BPH by global SDI quintile.

Results

Global Burden of Disease data over the 1990–2017 study period were summarized and global numbers and trends noted with other urological diseases for comparison. A total of 2 427 334 YLD were attributed to BPH in 2017 alone, almost three times more than those attributed to the next highest urological disease, prostate cancer (843 227 YLD). When stratified by SDI quintile, a much lower impact of BPH was found in the bottom three quintiles, despite this subset representing 66.9% of the 2017 world population.

Conclusions

Lower urinary tract symptoms attributed to benign prostatic hyperplasia exert a rapidly rising human burden far exceeding other urological diseases. As the population ages and men in a lower SDI enjoy increased life expectancy and decreased competing mortalities, a continually accelerating wave of LUTS/BPH can be forecast. These epidemiological trends have serious implications for the future allocation of resources and the global urological workforce.

Objectives

To describe the trend in the impact of lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH) on a global scale using the Global Burden of Disease (GBD) database.

Materials and Methods

Using the GBD database, worldwide data aggregated from registries and health systems from 1990 to 2017 were filtered for LUTS/BPH diagnoses. Calculation of years lived with disability (YLD) were compared with other urological diseases. YLD were calculated by a standardized method using assigned disability weights. The GBD-defined sociodemographic index (SDI) was used to assess impact of LUTS/BPH by global SDI quintile.

Results

Global Burden of Disease data over the 1990–2017 study period were summarized and global numbers and trends noted with other urological diseases for comparison. A total of 2 427 334 YLD were attributed to BPH in 2017 alone, almost three times more than those attributed to the next highest urological disease, prostate cancer (843 227 YLD). When stratified by SDI quintile, a much lower impact of BPH was found in the bottom three quintiles, despite this subset representing 66.9% of the 2017 world population.

Conclusions

Lower urinary tract symptoms attributed to benign prostatic hyperplasia exert a rapidly rising human burden far exceeding other urological diseases. As the population ages and men in a lower SDI enjoy increased life expectancy and decreased competing mortalities, a continually accelerating wave of LUTS/BPH can be forecast. These epidemiological trends have serious implications for the future allocation of resources and the global urological workforce.

Objectives

To describe the trend in the impact of lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH) on a global scale using the Global Burden of Disease (GBD) database.

Materials and Methods

Using the GBD database, worldwide data aggregated from registries and health systems from 1990 to 2017 were filtered for LUTS/BPH diagnoses. Calculation of years lived with disability (YLD) were compared with other urological diseases. YLD were calculated by a standardized method using assigned disability weights. The GBD-defined sociodemographic index (SDI) was used to assess impact of LUTS/BPH by global SDI quintile.

Results

Global Burden of Disease data over the 1990–2017 study period were summarized and global numbers and trends noted with other urological diseases for comparison. A total of 2 427 334 YLD were attributed to BPH in 2017 alone, almost three times more than those attributed to the next highest urological disease, prostate cancer (843 227 YLD). When stratified by SDI quintile, a much lower impact of BPH was found in the bottom three quintiles, despite this subset representing 66.9% of the 2017 world population.

Conclusions

Lower urinary tract symptoms attributed to benign prostatic hyperplasia exert a rapidly rising human burden far exceeding other urological diseases. As the population ages and men in a lower SDI enjoy increased life expectancy and decreased competing mortalities, a continually accelerating wave of LUTS/BPH can be forecast. These epidemiological trends have serious implications for the future allocation of resources and the global urological workforce.