Apalutamide versus bicalutamide in combination with androgen deprivation therapy for metastatic hormone sensitive prostate cancer.

The objective of this study is to compare the efficacy of apalutamide and bicalutamide in combination with androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively collected the data of about 330 patients with metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and August 2023. Sixty-one patients were administered apalutamide (240 mg/day) with androgen deprivation therapy (group A), and 269 patients were administered bicalutamide (80 mg/day) with androgen deprivation therapy (group B). Propensity score matching was used to adjust for clinical background factors between the two groups. PSA progression-free survival and overall survival were significantly longer in group A than in group B among the matched patients. Apalutamide therapy was a significant independent factor for OS in matched patients. The second progression-free survival of group A was significantly longer than that of group B in matched patients. Patients treated with apalutamide achieved ≥ 90% PSA decline from baseline faster and in larger numbers than those with bicalutamide. Apalutamide combined with ADT may be superior to bicalutamide alone in terms of OS and PSA-PFS in patients with mHSPC.

Screening for a practical method to monitor the status of patients with metastatic bladder cancer at the circulating cell-gene level.

Identifying a novel method to monitor metastatic bladder cancer status at the cell-gene level could lead to earlier appropriate therapeutic intervention and better outcomes. In this study, we evaluated a practical method to monitor the cancer status at the circulating cell-gene level before and after treatment in fourteen patients with metastatic bladder cancer who were indicated for systemic drug therapy. Patients were assessed via imaging before and after drug treatment, and cell-free DNA (cfDNA) analysis was performed to detect three parameters: cfDNA level, ERRB2 gene copy numbers, and telomerase reverse transcriptase (TERT) gene mutations. We hypothesized that decreased cfDNA levels, a normal copy number of ERB-B2 receptor tyrosine kinase 2 (ERBB2), and the absence of the TERT C228T mutation indicate cancer suppression. We found that a > 1.8-fold increase in cfDNA levels, increased copy number of ERBB2, or the existence of the TERT C228T mutation indicated disease progression. Stable cfDNA levels, normal ERBB2 copy number, and the absence of TERT C228T mutations indicate a stable cancer status. Collectively, our results show that the combination of cfDNA concentration, TERT mutation, and ERBB2 copy number may be useful for determining the efficacy of drug therapy in patients with metastatic bladder cancer.

Novel device for dividing core needle biopsy specimens to provide paired mirror image-like tissues for genetic and pathological tests.

In a world that seeks precision medicine, genetic testing is gaining importance in clinical decision making. We previously reported the utility of a novel tool for longitudinally dividing core needle biopsy (CNB) tissues into two filamentous tissues that can provide paired mirror image-like tissues (mirror-tissues) that spatially match each other. In this study, we investigated its application in gene panel testing in patients who underwent prostate CNB. Four hundred and forty-three biopsy cores were obtained from 40 patients. Of them, 361 biopsy cores (81.5%) were judged by a physician to be appropriate for dividing into two pieces using the new device, of which a histopathological diagnosis was successfully reached in 358 biopsy cores (99.2%). Among them, the quality and quantity of nucleic acid in 16 appropriately divided cores were assessed and found to be sufficient for gene panel testing, and histopathological diagnosis was successfully obtained from the remaining divided cores. The novel device for longitudinally-dividing CNB tissue provided mirror image-like paired-tissues for gene panel and pathology testing. The device might be a promising tool for obtaining genetic and molecular biological information, in addition to histopathological diagnosis, helping to advance personalized medicine.

Predictive factors for the efficacy of abiraterone acetate therapy in high-risk metastatic hormone-sensitive prostate cancer patients.

PURPOSE: There is a discrepancy in the efficacy of abiraterone acetate for overall survival (OS) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to identify predictive factors for the efficacy of abiraterone acetate for OS in high-risk mHSPC patients by analyzing them over a longer observation period. METHODS: Five hundred high-risk mHSPC patients were retrospectively identified at our hospital and affiliated hospitals in the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2022. Two hundred patients were treated with abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) combined with androgen deprivation therapy (ADT). A total of 300 patients were treated with bicalutamide (80 mg/day) in combination with ADT. RESULTS: OS was not significantly different between the two treatments in the overall cohort (p = 0.1643). In the subgroup without Gleason pattern 5 at the primary lesion, OS was significantly better in patients treated with abiraterone acetate than in those treated with bicalutamide (p = 0.0192). In the subgroup with Gleason pattern 5 at the primary lesion, no significant difference was found between the two treatments (p = 0.1799). Univariate and multivariate analyses in the subgroup without Gleason pattern 5 at the primary lesion suggested that abiraterone therapy may be an important and independent predictor of OS in high-risk mHSPC patients. CONCLUSION: The presence of Gleason pattern 5 at the primary lesion may be a predictor for high-risk mHSPC patients who could benefit from abiraterone acetate treatment.

Two-Step Method for Constructing a Quaternary Carbon Atom with a Geminal Divinyl Group from a Ketone.

A two-step synthesis of geminal divinyl compounds from ketones was developed. An allyl titanium reagent prepared from 1-phenylthio-4-trimethylsilyl-2-butene was reacted with a ketone, and the resulting tertiary alcohol was subjected to a Brønsted acid-mediated rearrangement reaction to generate a geminal divinyl compound. Introduction of another alkene moiety followed by ring closing metathesis resulted in a bicyclic compound possessing a vinyl group at the bridgehead position.