大島 将

BACKGROUND: Robot-assisted radical prostatectomy (RARP) is a preferred minimally invasive surgical treatment for prostate cancer. The number of elderly patients and those with cardiovascular and/or cerebrovascular issues undergoing surgery is increasing, and many of them are taking antithrombotic (AT) agents. However, the effect of AT agents on postoperative urinary recovery has not been adequately studied. In this study, we analyzed the differences in the postoperative recovery of urinary continence and oncological outcomes in patients undergoing RARP for localized prostate cancer between AT agent adherents and non-adherents. METHODS: A total of 394 patients who underwent conventional anterior RARP between February 2015 and February 2021 were categorized into two groups: those taking oral AT agents (AT group) and the control group. Urinary continence recovery, complications, and oncological outcomes were compared between the groups. A Cox proportional hazards analysis was performed to identify clinical factors that affect urinary continence recovery. RESULTS: The background data and bleeding complications did not differ significantly between the groups. The recovery of continence was significantly poorer in the AT group in terms of complete pad free (HR: 0.53 [95% CI: 0.39-0.71]) and use of ≤ 1 safety pad (HR: 0.74 [95% CI: 0.59-0.94]). The rate of anastomotic leakage on cystography was significantly higher in the AT group (20.9% vs. 6.7%). A univariate analysis revealed that taking antithrombotic agents, higher prostate-specific antigen levels, and a more advanced clinical stage were associated with a poor urinary continence recovery; a multivariate analysis showed that taking AT agents was an independent factor negatively associated with urinary continence recovery. There was no significant difference between the groups in the positive surgical margin rate (19.0% vs. 23.8%) or the biochemical-recurrence-free rate. CONCLUSION: Taking oral AT agents may be associated with poor urinary continence recovery after RARP.

Prostate cancer is an androgen-dependent malignancy that presents a marked treatment challenge, particularly after progression to the castration-resistant stage. Traditional treatments such as androgen deprivation therapy often lead to resistance, necessitating novel therapeutic approaches. Previous studies have indicated that some of the azolato-bridged dinuclear platinum(II) complexes (general formula: [{cis-Pt(NH3)2}2(μ-OH)(μ-azolato)]X2, where azolato = pyrazolato, 1,2,3-triazolato, or tetrazolato and X = nitrate or perchlorate) inhibit androgen receptor (AR) signaling. Therefore, here we investigated the potential of 14 such complexes as agents for the treatment of prostate cancer by examining their antiproliferative activity in the human prostate adenocarcinoma cell line LNCaP. Several of the complexes, particularly 5-H-Y ([{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](ClO4)2), effectively inhibited LNCaP cell growth, even at low concentrations, by direct modulation of AR signaling, and by binding to DNA and inducing apoptosis, which is a common mechanism of action of Pt-based drugs such as cisplatin (cis-diamminedichloridoplatinum(II)). Comparative analysis with cisplatin revealed superior inhibitory effects of these complexes. Further investigation revealed that 5-H-Y suppressed mRNA expression of genes downstream from AR and induced apoptosis, particularly in cells overexpressing AR, highlighting its potential as an AR antagonist. Thus, we provide here insights into the mechanisms underlying the antiproliferative effects of azolato-bridged complexes in prostate cancer.

Although hormone therapy is effective for the treatment of prostate cancer (Pca), many patients develop a lethal type of Pca called castration-resistant prostate cancer (CRPC). Dysregulation of DNA damage response (DDR)-related genes leads to Pca progression. Here, we explored DDR-related signals upregulated in CRPC tissues. We analyzed the gene expression profiles in our RNA-sequence (RNA-seq) dataset containing benign prostate, primary Pca, and CRPC samples. We identified six DDR-related genes (Ribonuclease H2 Subunit A (RNASEH2A), replication factor C subunit 2 (RFC2), RFC4, DNA Ligase 1 (LIG1), DNA polymerase D1 (POLD1), and DNA polymerase E4 (POLE4)) that were upregulated in CRPC compared with Pca tissues. By analyzing public databases and validation studies, we focused on RFC2 as a new biomarker. Functional analysis demonstrated that silencing of RFC2 expression inhibited cell proliferation and induced the expression of DNA damage and apoptosis markers in CRPC model cells. Furthermore, immunohistochemical (IHC) analysis revealed that high expression of RFC2 protein correlated with poor prognosis in patients with Pca and increased expression in CRPC tissues compared with localized Pca. Thus, our study suggests that six DDR-related genes would be important for Pca progression. RFC2 could be a useful biomarker associated with poor outcomes of patients with Pca.

OBJECTIVES: The analysis of the oncological outcomes and postoperative continence recovery between conventional robotic-assisted radical prostatectomy (cRARP) and Retzius-sparing RARP (rsRARP), and the effect of the tumor location on them. MATERIALS AND METHODS: A total of 317 patients who underwent cRARP (n = 228) or rsRARP (n = 89) from August 2017 to July 2020 were assessed. Patients were categorized into groups based on the tumor location by pathology. Positive surgical margin (PSM) rates and biochemical recurrence (BCR)-free survivals and continence recovery were compared between the two procedures. RESULTS: Patient age, prostate-specific antigen (PSA) levels, clinical stages, and Gleason score were not significantly different between the two groups. There was no significant difference in PSM rates (25.8% vs. 33.7%, p = 0.13) or BCR-free survivals (p = 0.28) between cRARP and rsRARP in patients. When tumor was located in the anterior lesion in the prostatectomy pathology, rsRARP was associated with significantly higher PSM rates than cRARP (53.3% in rsRARP vs. 27.0% in cRARP, p = 0.0086), while BCR-free survival did not vary significantly (hazard ratio: 2.15, p = 0.11). When tumors were identified in the posterior in prostatectomy pathology, PSM rates (28.8% in rsRARP vs. 24.7% in cRARP, p = 0.59) or BCR-free survivals (hazard ratio: 0.78, p = 0.51) did not differ significantly between the two groups. rsRARP yielded superior continence recovery in all time points compared to cRARP, which was not affected by the pathological tumor location. CONCLUSION: In posterior tumors, rsRARP results in similar oncological outcomes as cRARP with superior continence recovery, while in anterior tumors, rsRARP may associate with higher PSM rate, combined with improved continence recovery.

The objective of the study was to evaluate the risk of bleeding complications in patients undergoing robot-assisted radical prostatectomy (RARP) while taking antiplatelet (AP) and/or anticoagulant (AC) agents. We analyzed the data of 334 patients undergoing RARP from May 2015 to May 2019. Patients were categorized into AP, AC, and control groups; the bleeding complications were compared among them. The end points were the estimated blood loss, decrease in hemoglobin level, and bleeding complications. The patient characteristics did not differ significantly among groups, with the exception of ASA scores, which were significantly higher in the AP and AC groups vs. the control group. The estimated blood loss and hemoglobin decrease were not significantly different between the AP and AC groups and the control group. The frequency of bleeding complications did not differ significantly between the AP and the control groups, but was significantly higher in the AC vs. the control group (4.3% in the AP and 23.5% in the AC group vs. 3.7% in the control group; P = 0.63 and P < 0.01, respectively). There was no significant difference in bleeding complications between the AP continuation (continuation of a single AP) and the AP interruption group or between the heparin bridging and the AC interruption group. All bleeding complications observed in the AC group occurred after resuming AC therapy. RARP can be performed safely with continuation of a single AP, and in patients taking ACs by interrupting these agents or via heparin bridging, without increasing intraoperative bleeding, whereas postoperative bleeding complications may increase after resuming ACs.