Urologic Oncology-seminars and Original Investigations最新文献

Purpose: To determine the efficacy and safety of sequential transarterial embolization and percutaneous cryoablation of renal masses > 3 cm.

Materials and methods: Forty six patients underwent sequential transarterial embolization and percutaneous cryoablation of a renal mass > 3 cm (31 patients with mass > 4 cm) at two tertiary academic medical centers between 2014 and 2024. Primary efficacy was defined as the percentage of target tumors with no evidence of residual enhancement following the initial procedure. Secondary efficacy included tumors that underwent successful repeat ablation after identifying local tumor progression. Adverse events were classified according to the Society of Interventional Radiology criteria. Kaplan-Meier survival analysis was utilized to determine progression-free survival rates.

Results: The median tumor diameter was 4.5 cm (IQR 3.5-5.3 cm). Primary and secondary efficacy rates for T1a lesions were 93% and 100%, respectively. Primary and secondary efficacy rates for T1b lesions were 81% and 87%, respectively. The 1-year and 2-year progression-free survival rates were 94% and 87%, respectively, after a median imaging follow-up period over 1.6 years (IQR 0.9-3.1). The overall adverse event rate was 13% (6/46) and the severe adverse event rate was 4% (2/46). Both severe adverse events were related to post-procedural hemorrhage.

Conclusion: Sequential transarterial embolization and percutaneous cryoablation is a technically feasible and effective treatment option with a low severe adverse event rate for renal masses > 3 cm.

Introduction: The human telomerase reverse transcriptase (hTERT) upregulation is a common feature in many cancers. While telomerase activity is often linked to gene expression, the relationship between promoter methylation and hTERT levels can be complex. This study aimed to investigate the association between hTERT promoter hypermethylation and its expression for prognosis and pathogenesis of bladder cancer.

Methods: A total of 50 histologically confirmed bladder cancer tissue samples and matched adjacent normal controls were evaluated in a single-center prospective study. Promoter methylation was assessed by methylation-specific PCR (MS-PCR) targeting the CpG-rich hTERT promoter region, while protein expression was analyzed by immunohistochemistry using standardized scoring criteria. For validation, TCGA-BLCA data were analyzed for TERT mRNA expression, promoter methylation (TSS1500 and gene body regions), copy-number alterations (CNA), and survival outcomes. Correlation analyses and Kaplan-Meier plots were used for integrative assessment.

Results: Promoter hypermethylation of hTERT was detected in 90% of bladder cancers, with 80% showing high hTERT protein expression. A strong positive association between promoter hypermethylation and high protein expression was observed (P = 0.04). This was corroborated by TCGA data showing a significant upregulation of TERT mRNA in bladder tumors. The expression of hTERT was at its strongest at stage IV, though this trend was not significant in the larger TCGA cohort (P = 0.256) The large-scale survival analysis revealed no significant association between TERT expression with OS (P = 0.76), PFS (0.95), DFS (P = 0.88) and pan-cancer analysis. TERT amplification was linked to markedly higher expression levels, but weak correlation between methylation and expression at selected CpG loci and methylation at TSS1500 or gene body regions and expression CONCLUSION: Our findings demonstrate that hTERT promoter hypermethylation is paradoxically associated with increased protein expression in bladder cancer, possibly through disruption of repressor binding within the THOR region. Although hTERT expression lacks prognostic value, its consistent upregulation suggests potential use as a screening biomarker and supports exploration of telomerase-targeted therapeutic strategies.

Background: The roles of neoadjuvant chemotherapy (NAC) and lymph node dissection (LND), particularly their combined use, remain unclear in patients with non-muscle-invasive bladder cancer (NMIBC) undergoing radical cystectomy (RC).

Methods: Patients diagnosed with NMIBC and treated with RC were identified from the Surveillance, Epidemiology, and End Results database. Temporal trends in the utilization of NAC, LND, and their combination were analyzed. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS) across different treatment groups, including NAC, LND, and their combination, relative to no treatment.

Results: A total of 3,995 patients were included. The use of NAC and LND increased markedly over time. In the overall cohort, the combination of NAC and LND provided greater survival benefit (HR = 0.58, 95% CI 0.49-0.70, P < 0.001) than either treatment alone (HR = 0.73, 95% CI 0.66-0.81, P < 0.001). Subgroup analyses showed that the survival advantage of the combination compared with no treatment was not significant for nonurothelial or unspecified histology, low-grade disease, and Ta-Tis stage tumors. In patients with T1 high-grade urothelial carcinoma, NAC or LND alone improved OS (HR = 0.66, 95% CI 0.57-0.76, P < 0.001), and their combination yielded even greater benefit (HR = 0.52, 95% CI 0.42-0.65, P < 0.001), with significant advantages observed across nearly all subgroups.

Conclusion: In NMIBC patients undergoing RP, LND represented the primary driver of survival benefit, whereas NAC alone was not independently associated with improved outcomes. The combination of NAC and LND conferred an additional, incremental advantage over either modality alone, with the magnitude of benefit varying across patient characteristics. In the T1 high-grade urothelial carcinoma subgroup, both NAC and LND were associated with improved survival, with LND providing the dominant effect and the combined strategy yielding the greatest benefit, with advantages over no treatment observed across nearly all subgroups.

Introduction: Clear cell renal cell carcinoma (ccRCC), the most common kidney cancer subtype, has high rates of metastasis and recurrence. Its tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs), influences immune evasion and tumor progression. This study evaluated the prognostic significance of TAM and TIL subsets based on their phenotypes and spatial distribution within the TME.

Materials and methods: This retrospective study included 643 ccRCC patients who underwent surgery at Asan Medical Center between 2011 and 2013. Multiplex immunofluorescence staining was performed on tissue microarrays from central and peripheral tumor regions. Markers for M1/M2 macrophages and T cells were quantified using automated imaging software, and optimal cutoffs were defined using maximally selected rank statistics, with additional sensitivity analyses performed to assess robustness. Survival outcomes were assessed with Cox regression, and group comparisons used appropriate statistical tests.

Results: High central density of M2-like TAMs (CD68+CD206+) was associated with poor overall, metastasis-free, and progression-free survival (PFS) (P < 0.05). In contrast, high central density of M1-like TAMs (CD68+iNOS+) was associated with favorable PFS (P = 0.034). M2-like TAMs were more abundant than M1-like across all tumor regions. Peripheral CD3+ TILs were more frequent than in the center. Exploratory analyses showed weak correlations between immune cell densities and response to tyrosine kinase inhibitor therapy.

Conclusion: Distinct phenotypes and spatial distributions of TAMs were associated with prognostic outcomes in ccRCC. Central M2-like TAMs were associated with poor outcomes, while central M1-like TAMs were linked to favorable prognosis. TILs did not demonstrate independent prognostic value.

Background: First-line immune-oncology (IO) agents and VEGF-targeted tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) have complicated subsequent treatment decisions. This study describes real-world treatment patterns and clinical outcomes of mRCC patients in post-IO and TKI space in community oncology settings.

Methods: This retrospective cohort study utilized the iKnowMed electronic health record database to identify adult mRCC patients who received a subsequent line of therapy (LOT; index date) post-IO and TKI in combination or sequence between January 2018 and March 2023. Patients were followed from the index date until June 2023. Outcomes included time on treatment (ToT), Time to next treatment (TTNT), and overall survival (OS). A multivariate Cox proportional hazards regression model was used to evaluate the associations between index regimens and outcomes.

Results: The Study included 820 mRCC patients who received anticancer treatment post-IO and TKI therapies (median [IQR] age, 66 [58, 72] years; 72.6% male; 74.5% had an intermediate/poor IMDC risk score). Overall, 253 (30.9%) received index treatment in LOT2, 509 (62.1%) in LOT3, and 58 (7.1%) in LOT4+. Common treatments post-IO and TKI settings were cabozantinib (35.6%) and everolimus plus lenvatinib (9.5%). Median ToT for LOT2 was 2.5 months, LOT3 was 3.5 months, and LOT4 was 6.2 months. Median TTNT for LOT2, LOT3, and LOT4 were 6.4, 7.7, and 11.5 months, respectively. Median OS for LOT2, LOT3, and LOT4 were 18.0, 17.8, and 28.6 months, respectively.

Conclusions: This large cohort study presents one of the most comprehensive analyses of treatment patterns and clinical outcomes among patients with mRCC in the post-IO and TKI settings. TKI, with or without IO-based treatments, was the most preferred treatment and associated with improved survival. Novel therapies are needed in this patient population to improve long-term outcomes.

This review highlights recent data regarding antigens on the cell surface of prostate cancer cells or cells in the prostate cancer tumor microenvironment which may serve as targets for novel therapeutics. Emphasis is placed on clinical data involving human subjects. The biological role of each antigen discussed is described, as are the expression patterns of the antigen in relation to histologic subtype of prostate cancer. Most descriptions are based on histological or genomic data, and quantitative assessment via targeted immuno-PET when available. Some antigens such as prostate-specific membrane antigen (PSMA), TROP-2, six-transmembrane epithelial antigen of the prostate 1 (STEAP1), and PSCA are overexpressed primarily in prostate adenocarcinoma, while CEACAM5 or delta-like ligand 3 (DLL3) are more commonly expressed in neuroendocrine prostate cancer. CD46 may be overexpressed in both prostate adenocarcinoma and neuroendocrine prostate cancer. The expression pattern and relevance of human epidermal growth factor receptor 2 (HER2) as a therapeutic target in prostate cancer remains unclear. Fibroblast activation protein (FAP) is a cell-surface proteins more often expression on cancer fibroblasts in the tumor microenvironment. Ongoing investigation into novel targets for the treatment of prostate cancer continues to identify promising antigens which are overexpressed on the cell surface. Patterns of expression may vary based on histologic type, anatomic location, and treatment state of prostate cancer, and these factors will ultimately dictate the utility of novel therapeutic agents that are in development.