Clinical significance of early kinetics of C‑reactive protein in patients with advanced urothelial carcinoma treated with pembrolizumab: Flare response and baseline levels predict oncological outcomes.

Data on the C-reactive protein (CRP) flare response in patients with metastatic and unresectable urothelial carcinoma (mUC) are limited. The present study aimed to clarify the clinical significance of the CRP flare response in patients with mUC who received pembrolizumab. Between March 2018 and December 2022, patients with mUC who received pembrolizumab following chemotherapy were retrospectively reviewed.

Immunohistochemical Expression of p53 and FGFR3 Predicts Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma.

Locally advanced or metastatic urothelial carcinoma is a genomically and molecularly heterogeneous disease associated with various clinical outcomes. We aimed to evaluate the association between the status of p53/FGFR3 expression and the efficacy of enfortumab vedotin (EV) in metastatic urothelial carcinoma. We evaluated the association between p53 (abnormal vs.

The Omission of Upfront Treatment Intensification Does Not Adversely Affect Oncological Outcomes in a Subset of Castration-Highly Sensitive Metastatic Prostate Cancer.

Background/aim: In patients with metastatic castration-sensitive prostate cancer (mCSPC), upfront treatment intensification with the addition of new hormonal agents and/or docetaxel to androgen deprivation therapy (ADT) is recommended. However, this modality is potentially excessive in a subset of these patients. This study aimed to identify patients who may be eligible to omit upfront treatment intensification.

Melatonin Inhibits Chemical Carcinogen-mediated Malignant Transformation of Urothelial Cells: Evidence.

Background/aim: The efficacy of melatonin and its biological significance in human bladder cancer remain poorly understood. This study aimed to investigate the functional role of melatonin in urothelial carcinogenesis.

Materials And Methods: In human normal urothelial SVHUC cells with exposure to the chemical carcinogen 3-methylcholanthrene, we assessed the effects of melatonin on the neoplastic/malignant transformation.

Optimal Number of Cycles of First-line Platinum-based Chemotherapy for Metastatic Urothelial Carcinoma.

Background/aim: In recent years, switch maintenance after platinum-based chemotherapy has been a standard of care. However, the appropriate number of systemic chemotherapy cycles against advanced-stage urothelial carcinoma (UC) remains unclear. This study assessed the survival outcomes of first-line platinum-based chemotherapy according to treatment cycles in patients with metastatic disease.

Latrophilin-3 as a downstream effector of the androgen receptor induces urothelial tumorigenesis.

Emerging evidence indicates that androgen receptor (AR) signaling plays a critical role in the pathogenesis of male-dominant urothelial cancer. Meanwhile, latrophilins (LPHNs), a group of the G-protein-coupled receptor to which a spider venom latrotoxin is known to bind, remain largely uncharacterized in neoplastic diseases. The present study aimed to determine the functional role of LPHN3 (encoded by the ADGRL3 gene), in association with AR signaling, in urothelial tumorigenesis.

Mineralocorticoid receptor signaling inhibits bladder cancer progression.

The biological or clinical significance of mineralocorticoid receptor (MR) in urothelial cancer remains largely unknown. The present study aimed to determine the functional role of MR in bladder cancer progression. In two of the human bladder cancer lines expressing MR, treatment with a natural MR ligand, aldosterone, significantly reduced cell proliferation and migration, which was restored by three MR antagonists clinically used, spironolactone (except colony formation of androgen receptor-positive cells cultured in the presence of androgens), eplerenone, and esaxerenone.

Efficacy of Platinum-based Chemotherapy in Patients With Metastatic Urothelial Carcinoma With Variant Histology.

Background/aim: Variant urothelial carcinoma (VUC, defined herein as urothelial carcinoma with any histological variant) is frequently observed at an advanced stage. However, the efficacy of systemic chemotherapy against VUC in metastatic disease has rarely been reported. This study assessed the therapeutic response and survival outcomes of platinum-based chemotherapy as first-line treatment in patients with metastatic VUC.

Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study.

Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease.

Inhibition of aldo-keto reductase 1C3 overcomes gemcitabine/cisplatin resistance in bladder cancer.

Systemic chemotherapy with gemcitabine and cisplatin (GC) has been used for the treatment of bladder cancer in which androgen receptor (AR) signaling is suggested to play a critical role. However, its efficacy is often limited, and the prognosis of patients who develop resistance is extremely poor. Aldo-keto reductase 1C3 (AKR1C3), which is responsible for the production of a potent androgen, 5α-dihydrotestosterone (DHT), by the reduction of 5α-androstane-3α,17β-dione (5α-Adione), has been attracting attention as a therapeutic target for prostate cancer that shows androgen-dependent growth.

Initial-to-nadir Prostate-specific Antigen Ratio Predicts Response to First-line Enzalutamide in Metastatic Castration-resistant Prostate Cancer.

Background/aim: No practical biomarkers predict the response to enzalutamide in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). The present study aimed to evaluate the prognostic value of the initial-to-nadir prostate-specific antigen (PSA) ratio (I/N PSA) in primary hormone therapy for metastatic hormone-naïve prostate cancer associated with the response to first-line enzalutamide in mCRPC.

Patients And Methods: Twenty-eight patients with mCRPC received first-line enzalutamide to determine the associations between I/N PSA in combined androgen blockade and clinical outcomes.

Efficacy and Tolerability of Enfortumab Vedotin for Metastatic Urothelial Carcinoma: Early Experience in the Real World.

Background/aim: This study retrospectively investigated the impact of enfortumab vedotin (EV) monotherapy on the oncological outcome, safety profile, and health-related quality of life (HRQoL) in patients with metastatic urothelial carcinoma.

Patients And Methods: We assessed 26 consecutive patients who had received EV monotherapy after failure of platinum-based chemotherapy and immune checkpoint blockade therapy at our single institution from December 2021 to January 2023. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and EORTC QLQ-C30 as an HRQoL instrument were evaluated.

Second-Line Systemic Therapy for Highly Aggressive Neuroendocrine Prostate Cancer.

Neuroendocrine prostate cancer (NEPC) is generally an aggressive form of prostate cancer that can arise de novo or develop as a castration-resistant mechanism. While first-line platinum-based chemotherapy is effective against NEPC, its limited response duration and subsequent treatments pose significant clinical challenges. Standard second-line treatments have not been established due to the limited data available.

Protective role of mineralocorticoid receptor signaling in urothelial tumorigenesis.

The expression status of mineralocorticoid receptor (MR) and its biological significance in human urothelial carcinoma remain unknown. The present study aimed to determine the functional role of MR in the development of urothelial cancer. In human normal urothelial SVHUC cells with exposure to a chemical carcinogen 3-methylcholanthrene (MCA), we assessed the effects of a natural MR ligand, aldosterone, and 3 MR antagonists, including spironolactone, eplerenone, and esaxerenone, as well as knockdown of MR via shRNA virus infection, on their neoplastic/malignant transformation.

Differential impact of proton pump inhibitor on survival outcomes of patients with advanced urothelial carcinoma treated with chemotherapy versus pembrolizumab.

Objectives: We clarified the effect of concomitant proton pump inhibitor use on oncological outcomes in patients with advanced urothelial carcinoma treated either with chemotherapy or immune checkpoint inhibitor.

Methods: We retrospectively reviewed patients with advanced urothelial carcinoma who received paclitaxel-gemcitabine therapy or pembrolizumab after platinum-based chemotherapy. The patients were divided into four groups based on the treatment regimen and the concomitant use of proton pump inhibitor.

Prostate-specific Antigen Kinetics During Androgen-deprivation Therapy Predict Response to Enzalutamide in Metastatic Castration-resistant Prostate Cancer.

Background/aim: No practical predictive biomarkers exist to date for the response to androgen receptor-axis targeted (ARAT) therapies in metastatic castration-resistant prostate cancer (mCRPC). This study investigated whether prostate-specific antigen (PSA) kinetics in primary androgen-deprivation therapy for advanced hormone-sensitive prostate cancer may be associated with the response to ARAT agents in mCRPC.

Patients And Methods: This study assessed 102 patients with mCRPC treated with enzalutamide or abiraterone to evaluate the associations between clinical outcomes and PSA kinetics, including the ratio of initial to nadir PSA (I/N PSA) level in primary combined androgen blockade.

Association Between Body Mass Index and Outcomes in Patients With Urothelial Carcinoma Treated With Pembrolizumab.

Background/aim: We aimed to clarify the association between body mass index (BMI) and clinical outcomes of pembrolizumab treatment for advanced urothelial cancer (UC).

Patients And Methods: We retrospectively reviewed the records of patients with advanced UC who received pembrolizumab after chemotherapy between March 2018 and December 2021. Patients were divided according to BMI into the non-overweight group (BMI <25 kg/m) and the overweight group (BMI ≥25 kg/m).

Immediate Prostate-specific Antigen Decline After Enzalutamide Following Abiraterone Predicts Survival in Castration-resistant Disease.

Background/aim: Although the sequential use of abiraterone and enzalutamide is not recommended because of possible cross-resistance, many patients with metastatic castration-resistant prostate cancer (mCRPC) are receiving sequential abiraterone and enzalutamide in the real world, and a subset of patients can benefit from sequential therapy with these drugs. This study aimed to identify patients who could benefit from the sequential use of enzalutamide after abiraterone use.

Patients And Methods: We included 70 patients with mCRPC who received enzalutamide sequentially following abiraterone treatment.

Impact of the Use of Proton Pump Inhibitors on Pembrolizumab Effectiveness for Advanced Urothelial Carcinoma.

Background/aim: This study aimed to clarify the impact of proton pump inhibitors (PPIs) on oncological outcomes in patients who received pembrolizumab for advanced urothelial carcinoma (UC).

Patients And Methods: Forty advanced UC patients treated with pembrolizumab were retrospectively reviewed and divided into two groups (PPI: 15 patients; without PPI: 25 patients). Tumor response and survival were compared between these groups.

Prognostic Significance of 3-Month Prostate-specific Antigen Level Following Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer.

Background/aim: We examined the prognostic use of the 3-month prostate-specific antigen (PSA3m) level after androgen-deprivation therapy in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC).

Patients And Methods: The present study included 145 patients with mHSPC who received primary androgen-deprivation therapy.

Results: The optimal cutoff PSA3m value for prediction of 5-year overall survival was 2.

Impact of C-reactive Protein Flare Response in Patients With Advanced Urothelial Carcinoma Who Received Pembrolizumab.

Background/aim: To clarify the clinical significance of the temporary elevated C-reactive protein (CRP) levels followed by a decrease below baseline (CRP flare response) after administration of pembrolizumab to patients with advanced urothelial carcinoma (UC).

Patients And Methods: We retrospectively reviewed 31 patients with advanced UC who received pembrolizumab. Patients were categorized into 3 groups (flare-responder, responder, non-responder) according to early CRP kinetics.

Treatment of Metastatic Castration-resistant Prostate Cancer: Are PARP Inhibitors Shifting the Paradigm?

Remarkable developments in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been achieved over the past decade. Although targeting the novel androgen receptor axis and using chemotherapeutic agents have improved survival, mCRPC is still a lethal disease. A better molecular characterization of cancer resulted in the determination of the important role of homologous recombination repair (HRR) genes in cancer development, and poly (ADP-ribose) polymerase (PARP) is one of the most attractive therapeutic targets.

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer.

The underlying molecular mechanisms of resistance to cisplatin-based systemic chemotherapy in bladder cancer patients remain to be elucidated, while the link between androgen receptor (AR) activity and chemosensitivity in urothelial cancer has been implicated. Our DNA microarray analysis in control vs. AR knockdown bladder cancer lines identified GULP1 as a potential target of AR signaling.