Predictors of early progressive disease and antitumor effects by metastatic site in renal cell carcinoma treated with ipilimumab plus nivolumab.

Background: Despite durable benefits of ipilimumab and nivolumab in metastatic renal cell carcinoma (mRCC), early progressive disease (PD), defined as disease progression within 3 months, occurs, and its predictors remain unclear. We aimed to investigate the clinical factors associated with early PD in patients with mRCC treated with this regimen.

Methods: A retrospective analysis of a multi-institutional database identified 193 patients with mRCC treated with ipilimumab plus nivolumab.

Role of Cytoreductive Nephrectomy in the Immune Checkpoint Inhibitor Era: A Multicenter Collaborative Study.

Objectives: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy.

Methods: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment.

Comparison of Oncological Outcomes of Conventional Androgen Deprivation Therapy (ADT) and ADT Plus Androgen Receptor Signaling Inhibitor in Older Patients With Metastatic Castration-Sensitive Prostate Cancer.

Objectives: Evidence on upfront androgen receptor signaling inhibitor (ARSI) plus androgen deprivation therapy (ADT) in the older population with metastatic castration-sensitive prostate cancer (mCSPC) is scarce. We aimed to compare the oncological outcomes of ARSI plus ADT (upfront doublet therapy) and conventional ADT in mCSPC patients aged ≥ 75 years in a real-world clinical practice.

Methods: Subjects were mCSPC patients aged ≥ 75 years who received upfront doublet therapy (upfront doublet group) or ADT, either alone or in combination with bicalutamide (conventional ADT group) as a first-line systemic therapy.

Rash and Endocrine Disorders Predict Improved Survival in Metastatic Renal Cell Carcinoma Treated With Immunotherapy.

Background/aim: Immune-related adverse events (irAEs) are associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immuno-oncology therapy. However, various irAEs occur during such therapy. In this study, we analyzed the association between irAEs and prognosis of patients with mRCC treated with nivolumab and ipilimumab.

Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy.

Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy.

Prognostic Impact of Initial Prostate-Specific Antigen in Metastatic Hormone-Sensitive Prostate Cancer Patients With Extensive Bone Metastases Under Androgen Receptor Signaling Inhibitor.

Objectives: We evaluated the association between initial prostate-specific antigen (iPSA) levels and prognosis in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) and extensive bone metastases treated with androgen receptor signaling inhibitors (ARSI).

Subjects And Methods: This retrospective study included 276 de novo high-risk mHSPC patients with extensive bone metastases (extent of disease [EOD] score ≥ 2) who received ARSI as first-line therapy. The data were collected from institutions participating in the ULTRA Japan Study group.

PRC2-mediated apoptosis evasion is a therapeutic target of MDS/AML harboring inv(3)/t(3;3) and monosomy 7.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) harboring both inv(3)/t(3;3) and monosomy 7 (-7) are highly aggressive myeloid cancers of which molecular pathogenesis and therapeutic vulnerability remain elusive. High throughput drug screens, CUT&Tag/RNA sequence, and functional assays using human MDS/AML cells revealed that EZH2 inhibitors efficiently induce apoptosis preferentially in MDS/AML with inv(3)/t(3;3) and -7 through the activation of GADD45γ-p38-p53 axis. EVI1 activated in 3q-rearranged MDS/AML was responsible for silencing by direct binding to its consensus sequence within GADD45γ promoter and recruitment of PRC2 complex via interaction with EZH2, which can be therapeutically targeted by EZH2 inhibition.

Dual compartment utility of BRET-based biosensors for PPP2R5A/B56α, a cancer-associated B regulatory subunit of PP2A.

Protein phosphatase 2A (PP2A), a pivotal serine/threonine phosphatase, plays a crucial role in cellular regulation and tumor suppression. Dysregulation of PP2A complex, particularly the Aα subunit and B56 family, is linked to malignancies through altered substrate interactions, exemplified by c-MYC dynamics. Given the challenges in identifying PP2A substrates-owing to the enzyme's expansive substrate range, transient interaction profiles, and complex regulatory mechanisms-we employed bioluminescence resonance energy transfer (BRET) sensors.

Cancer-induced Pain Is Associated With Poor Overall Survival of Urothelial Carcinoma Patients Treated With Enfortumab Vedotin.

Background/aim: Cancer-induced pain (CIP) exacerbates patient's quality of life. However, it is unknown whether CIP is associated with survival in urothelial carcinoma (UC) patients treated with enfortumab vedotin (EV). This study retrospectively investigated the prognostic significance of CIP in EV-treated UC patients.

Clinical significance of primary tumor progression in metastatic hormone-sensitive prostate cancer.

Background: Clinical significance of primary tumor progression in patients with metastatic hormone-sensitive prostate cancer (mHSPC) is unclear.

Methods: Clinical data from 987 patients with mHSPC from multiple institutions between September 1999 and November 2023 were reviewed. The prognostic impact of primary tumor progression was examined along with other clinical parameters.

Deciphering RCC immunotherapy outcomes: insights from a Japanese multi-institutional study on the CANLPH score's impact.

Purpose: The purpose of this study is to determine the utility of the CANLPH score as a predictive biomarker for patients with advanced and metastatic renal cell carcinoma (a/mRCC). By validating its prognostic value, this study aims to contribute to more personalized treatment strategies for a/mRCC.

Methods: In a multicenter retrospective study by the JK-FOOT consortium, we analyzed data from 309 a/mRCC patients undergoing ICI-based therapy.

Association of body mass index and tumor response in metastatic urothelial carcinoma treated with enfortumab vedotin: data from the ULTRA-Japan consortium.

Background: Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, has been available as standard care for metastatic urothelial carcinoma (mUC) patients who have progressed after platinum-based chemotherapy and checkpoint inhibitors (CPIs). However, the association between body mass index (BMI) and clinical outcomes for EV remains unknown.

Methods: We analyzed the records of 123 mUC patients who received EV.

Characterization of PSA dynamics and oncological outcomes in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors.

Background: This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Patients And Methods: A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed.

Predicting time to castration resistance with androgen-receptor signaling inhibitors in hormone-sensitive prostate cancer: data from ULTRA-Japan Consortium.

Background: Androgen-receptor signaling inhibitors (ARSIs) become the new standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). It is unknown whether time to castration resistance (TTCR), when using the first-line ARSIs, offers predictive value in mHSPC. We sought to assess the clinical outcomes for mHSPC patients treated with first-line ARSIs focusing on the TTCR.

Mechanistic insights into lethal hyper progressive disease induced by PD-L1 inhibitor in metastatic urothelial carcinoma.

Hyper progressive disease (HPD) is a paradoxical phenomenon characterized by accelerated tumor growth following treatment with immune checkpoint inhibitors. However, the pathogenic causality and its predictor remain unknown. We herein report a fatal case of HPD in a 50-year-old man with metastatic bladder cancer.

Clinical outcomes and prognostic factors in metastatic nonclear cell renal cell carcinoma treated with immuno-oncology combination therapy.

Background: Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy.

Sex difference and immunosenescence affect transplantation outcomes.

Kidney transplantation is a well-established alternative to renal replacement therapy. Although the number of patients with end-stage renal disease (ESRD) is increasing, the availability of kidney for transplantation is still insufficient to meet the needs. As age increases, the prevalence of ESRD increases; thus, the population of aged donors and recipients occupies large proportion.

The medical cost and outcome of desensitization protocol in kidney transplantation recipients with high immunological risks.

Background: Kidney transplantation is a well-established alternative in renal replacement therapy. Compared with hemodialysis, low-immunological-risk kidney transplantation can reduce the medical treatment costs associated with end-stage renal disease. However, there are few reports on whether high-immunological-risk kidney transplantation reduces the financial burden on governments.

Nephron-sparing ureteroscopic surgery vs. radical nephroureterectomy: comparable survival-outcomes in upper tract urothelial carcinoma.

Purpose: This study investigates the utility of ureteroscopic surgery (URS) as an alternative to radical nephroureterectomy (RNU) in managing upper tract urothelial carcinoma (UTUC), with a focus on survival outcomes and re-evaluation of current the European Association of Urology guidelines criteria.

Methods: We conducted a retrospective, multi-institutional review of 143 UTUC patients treated with URS (n = 35) or RNU (n = 108). Clinicopathological factors were analyzed, and survival outcomes were assessed using Kaplan-Meier analysis and Cox proportional-hazards models.

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer.

Background: There is little evidence of abiraterone acetate (AA) plus prednisone for patients with non-metastatic castration-resistant prostate cancer (nmCRPC). In this study, we conducted a comparative analysis of real-world survival outcomes between AA plus prednisone and enzalutamide (Enz) in patients with nmCRPC, utilizing our consortium dataset.

Materials And Methods: The clinical records of 133 nmCRPC patients treated with first-line Enz or AA plus prednisone were analyzed.

Usefulness of Dietary Salt Restriction in Kidney Transplant Recipients: Analysis of Blood Pressure Levels Depending on the Differences in the Levels of Salt Intake.

Background: Sodium retention causes post-transplant hypertension, and sodium restriction is recommended in kidney transplantation recipients. We investigated the changes in salt intake and age-specific differences in salt intake over the post-transplant periods and considered what guidance is important for salt reduction tailored to individual recipients.

Methods: We calculated salt intake for 38 recipients who underwent kidney transplantation from August 2013 to August 2018 using Tanaka's equation and extracted their blood pressure (BP) levels.

Unplanned hemodialysis initiation and low geriatric nutritional risk index scores are associated with end-stage renal disease outcomes.

Patients with end-stage renal disease (ESRD) have a low nutritional status and a high mortality risk. The geriatric nutritional risk index (GNRI) is a predictive marker of malnutrition. However, the association between unplanned hemodialysis (HD) and GNRI with mortality remains unclear.