Low-dose abiraterone plus Olaparib as a late-line treatment for mCRPC patients without BRCA1/2 mutations: a multicenter retrospective pilot study.

Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA-PFS was 8 months (IQR: 6.5-11.5), with a median follow-up duration of 39.0 months (IQR: 27.5-64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.

Disitamab vedotin in combination with immune checkpoint inhibitors for locally and locally advanced bladder urothelial carcinoma: a two-center's real-world study.

Objective: Our study aims to assess the effectiveness and safety profile of Disitamab Vedotin (DV, RC48-ADC), an innovative humanized anti-HER2 antibody conjugated with tubulin-disrupting antimitotic drug monomethyl auristatin E (MMAE) via a cleavable peptide linker. This treatment combined immune checkpoint inhibitors as part of the bladder sparing approach for selected patients suffering from locally and locally advanced bladder urothelial carcinoma. Patients and methods: We conducted a two-center, real-world study involving locally advanced urothelial carcinoma (UC) patients. Patients were classified based on HER2 expression (IHC 3+/2+/1+) or lack of HER2 expression (IHC 0). The primary endpoint was the objective response rate (ORR), assessed by the investigator following the criteria of RECIST V1.1. Secondary endpoints encompassed the pathological complete response rate (pCR), pathological partial response rate (pPR), and pathological stable disease (pSD), along with recurrence-free survival (RFS), the pathological downstaging rate, and the safety profile of the treatment. Results: In this study, nine patients were enrolled, with a median follow-up duration of 12.0 months. The overall confirmed ORR was 88.9%, Five patients achieved a complete response (CR), and three patients achieved a partial response (PR). The radiological complete response (rCR) aligned perfectly with pCR. The median radiological progression-free survival (rPFS) spanned 12.0 months (range from 8.0 to 17.0 months). One patient diagnosed with disease progression (PD) underwent a radical cystectomy. The pathological stage evolved from T2N0M0 to T3aN2M0, followed by adjuvant chemotherapy with a gemcitabine-cisplatin (GC) combination radiotherapy. At the 9-month follow-up, neither recurrence nor metastasis was observed. The rate and intensity of complications were manageable among these patients, with no evidence of grade 4 and 5 adverse events. Conclusion: The combination of DV and PD-1 demonstrated considerable activity in the objective response rate (ORR) in patients with HER2 IHC 0/1+/2+/3+ muscle-invasive bladder cancer (MIBC), along with the longest reported median radiological progression-free survival (rPFS) to date. With an extended duration of treatment, the safety profile of DV plus PD-1 was also confirmed to be manageable.

Association Between CYP17A1, CYB5A Polymorphisms and Efficacy of Abiraterone Acetate/Prednisone Treatment in Castration-Resistant Prostate Cancer Patients.

PURPOSE: The purpose of this study was to investigate the association between single nucleotide polymorphisms (SNPs) of CYP17A1, CYB5A and the efficacy of abiraterone acetate treatment in patients with castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Data were collected from 58 CRPC patients who had been treated with abiraterone acetate/prednisone (AA/P). The SNPs rs743572 and rs10883783 on CYP17A1 and SNPs rs1790834 and rs1790858 on CYB5A were assayed, and their relationship with prostate-specific antigen (PSA) response in patients after AA/P treatment, overall survival (OS) and progression-free survival (PFS) were analyzed by logistic regression, Cox regression, Kaplan-Meier and Log rank analyses. RESULTS: The SNP rs1790834 on CYB5A showed significant association with PSA response in CRPC patients treated with AA/P (P < 0.05), but rs743572, rs10883783 and rs1790858 did not. The rs1790834 variant significantly decreased both PFS and OS (P < 0.05). CONCLUSION: The CYB5A rs790834 genotype is a novel SNP related to CRPC and may be used as a biomarker for CRPC treatment.

Effect of SMYD3 on biological behavior and H3K4 methylation in bladder cancer.

PURPOSE: Our goal was to investigate the effect of SMYD3 on the biological behavior and histone 3 lysine-4 (H3K4) methylation of bladder cancer (BLAC). PATIENTS AND METHODS: qRT-PCR identified that SMYD3 expression level in BLAC cell lines (T24, 5637, BUI-87 and J-82) and human normal uroepithelial cell line SV-HUC1. We also constructed green fluorescence protein lentiviral vector using the gene short hairpin RNA (shRNA) system. We used Western blot to analyze the SMYD3, H3K4me1, H3K4me2 and H3K4me3 expression levels in shRNA transfection lines. We also performed a colony-forming assay to determine colony-forming ability, cell counting kit-8 for cell proliferation detection, Transwell assay to determine cell migration and invasion and Annexin V-FITC/PI double staining to analyze cell apoptosis. RESULTS: The SMYD3 expression level was significantly higher in BLAC cell lines (T24, 5637, BUI-87 and J-82) than in human normal uroepithelial cell line SV-HUC1, and exhibited the highest expression level in T24 cells, among the cell lines tested. qRT-PCR and Western blot analysis results showed that SMYD3 was successfully suppressed in shRNA transfection lines, and identified that SMYD3 suppression resulted inhibited H3K4me2 and H3K4me3 but not H3K4me1. SMYD3 knockdown cells accelerated cell apoptosis and exhibited low cell colony-forming ability, proliferation ability, inhibition of cell migration and invasion compared with normal cells. CONCLUSION: SMYD3 may be activated in BLAC cells to increase H3K4 activity to modulate cell proliferation, migration and invasion ability. The data will be a useful source for future therapy.

Obesity was an independent risk factor for febrile infection after prostate biopsy: A 10-year single center study in South China.

To detect the best antibiotic protocol for prostate biopsy and to assess the potential risk factors postbiopsy in Chinese patients.A total of 1526 patients underwent biopsy were assessed retrospectively. The effect of 3 antibiotic protocols was compared, including fluoroquinolone (FQ) monotherapy, third-generation cephalosporin combined with FQ and targeted antibiotics according to the prebiopsy rectal swab culture result. Postbiopsy infection (PBI) was defined as fever and/or active urinary tract symptoms such as dysuria or frequency with pyuria and/or leucocytosis, sepsis is defined as the presence of clinically or microbiologically documented infection in conjunction with systemic inflammatory response syndrome. The relationship between infections and clinical characteristics of patients was assessed. Data were first picked out in univariate analysis and then enter multivariate logistic regression.Thirty-three (2.2%) patients developed febrile infection. The combination antibiotic prophylaxis could significantly decrease the rate of PBI than FQ monotherapy (1.0% vs 4.0%, P = .000). The infection rate of the targeted antibiotic group was 1.1%, but there was no significant statistic difference compared with FQ alone (P = .349). Escherichia coli was the most predominant pathogen causing infection. Rectal swab revealed as high as 47.1% and 36.0% patients harbored FQ resistant and ESBL-producing organisms, respectively. In univariate analysis, overweight (BMI between 25 and 28 kg/m), obesity (BMI > 28 kg/m), diabetes were picked out as potential risk factors. Obesity remained as risk factor (OR = 12.827, 95% CI: 0.983-8.925, P = .001) while overweight and diabetes were close to significance (P = .052, .053, respectively).The combined cephalosporin with FQ prophylaxis could significantly decrease the risk of infectious complications. Obesity was an independent risk factor for PBI.

Clinical features of treatment-naive patients with hepatitis B virus infection: A community-based survey from high- and intermediate-hepatitis B endemicity regions in Southeast China.

The aim of study was to investigate the clinical features of treatment-naive patients in 2 regions with high- and intermediate-hepatitis B endemicity level in Southeast China and provide the baseline data for monitoring health or planning therapy.This study included 8207 cases of treatment-naive patients with hepatitis B virus (HBV) infection from Yuhuan (YH, high-hepatitis B endemicity region) and Shaoxing (SX, intermediate-hepatitis B endemicity region) during 2014-2015. Clinical data were collected from the patients. Blood samples were kept for detecting hepatitis B surface antigen, hepatitis B envelope antigen (HBeAg), hepatitis B envelope antibody, hepatitis B surface antibody, hepatitis B core antibody, liver function, HBV deoxyribonucleic acid, and alpha-fetoprotein. All persons underwent B ultrasound to exclude liver cirrhosis or cancer.Of all 8207 HBsAg-positive patients, 52.9% patients were in the low-replication (LR) stage and 30.3% in the HBeAg-negative chronic hepatitis B (ENH) stage; 8.8% cases were in the ENH stage with elevated alanine aminotransferase (ALT). More male than female patients were in immune clearance (IC) or ENH stages with elevated ALT (10.4% vs 4.8%, 12.1% vs 5.3%, respectively, P < .05). The percentage of patients in IC and immune tolerant (IT) stages declined with increasing age, whereas the percentages of ENH with elevated ALT stage were highest in 40 to 60 years.The percentage of patients in IT and IC stages was higher in YH than in SX (9.4% vs 3.8%, 9.9% vs 4.2%, respectively, P < .05). More patients had HBVDNA≥10 IU/mL in YH than in SX (24.6% vs 16.0%, P < .05), and more male than female patients had HBVDNA≥10 IU/mL(24.5% vs 17.9%, P < .05).Clinical features varied in treatment-naive patients with HBV infection between different genders and regions. More attention should be paid to the surveillance and therapy of patients in YH especially male patients for the prevention and prognosis of hepatitis B.