Theranostics (therapy + diagnosis) targeting prostate-specific membrane antigen (PSMA) is an emerging therapeutic modality that could alter treatment strategies for prostate cancer. Although PSMA-targeted radioligand therapy (PSMA-RLT) has a highly therapeutic effect on PSMA-positive tumor tissue, the efficacy of PSMA-RLT depends on PSMA expression. Moreover, predictors of treatment response other than PSMA expression are under investigation. Therefore, the optimal patient population for PSMA-RLT remains unclear. This review provides an overview of the current status of theranostics for prostate cancer, focusing on PSMA ligands. In addition, we summarize various findings regarding the efficacy and problems of PSMA-RLT and discuss the optimal patient for PSMA-RLT.
Enzalutamide (Enz) is a second‐generation androgen receptor (AR) antagonist for castration‐resistant prostate cancer (CRPC) therapy, and it prolongs survival time in these patients. However, during Enz treatment, CRPC patients usually acquire resistance to Enz and often show cross‐resistance to other AR signaling inhibitors. Although glucocorticoid receptor (GR) is involved in this resistance, the role of GR has not yet been clarified. Here, we report that chronic Enz treatment induced GR‐mediated glucose transporter 4 (GLUT4) upregulation, and that upregulation was associated with resistance to Enz and other AR signaling inhibitors. Additionally, inhibition of GLUT4 suppressed cell proliferation in Enz‐resistant prostate cancer cells, which recovered from Enz resistance and cross‐resistance without changes in GR expression. Thus, a combination of Enz and a GLUT4 inhibitor could be useful in Enz‐resistant CRPC patients.
Background and Objectives: This study was conducted to identify whether surgical stress during the peri-operative period of robot-assisted radical prostatectomy might affect biochemical recurrence in patients with positive surgical margins.Methods: Participants in the present study were 324 consecutive patients with localized prostate cancer who underwent robot-assisted radical prostatectomy between February 2013 and June 2018. Positive surgical margins were diagnosed in 61 of them. Patients with positive surgical margins were divided into those with (n = 19) and those without (n = 42) biochemical recurrence. Lymph node dissection, estimated blood loss, inhalation anesthetic volume, and surgical duration were evaluated as indicators of surgical stress. White blood cell count, C-reactive protein, body temperature, and usage of analgesics were postoperatively evaluated as surrogate markers of surgical stress. The associations between factors, including patients' characteristics and pathological features, and biochemical recurrence were investigated.Results: In univariate analyses, surgical duration (P = 0.004), D'Amico risk class (P = 0.002), Gleason score (P = 0.022) and the number of positive cores in prostate biopsy (P = 0.009) were statistically significantly associated with biochemical recurrence. In multivariate analyses, only surgical duration was significantly associated with biochemical recurrence (P = 0.042), at a cut-off value of surgical duration of 228.5 minutes.Conclusions: Prolonged surgical duration is associated with biochemical recurrence in patients with positive surgical margins. Thus, surgical duration should be limited as much as possible to reduce surgical stress, which might cause biochemical recurrence.
Background/Aim: The aim of the study was to evaluate the risk of venous thromboembolism (VTE) after robot-assisted radical prostatectomy (RARP) and discuss whether a uniform prophylaxis for VTE after radical prostatectomy is also suitable for robotic surgery. On this context, we investigated the incidence and risk factors of VTE, including asymptomatic events, after RARP compared to transurethral resection of bladder tumor (TUR-BT). Patients and Methods: The participants were 209 patients with localized prostate cancer who underwent RARP, and 93 patients who underwent TUR-BT as controls. The incidence and risk factors of VTE, including deep vein thrombosis and pulmonary embolism, were systemically investigated seven days after surgery using contrast-enhanced computed tomography. Results: Of the 209 RARP patients, 5.7% (12/209) patients had VTE. All events were asymptomatic and the incidence of VTE was not significantly different between the two surgeries (p=0.90). In multivariate analyses, neoadjuvant androgen deprivation therapy (ADT) (p=0.006), D-dimer value on postoperative day 1 (p=0.001) and lymphocele formation (p=0.043) were significantly associated with VTE after RARP. Conclusion: The risk of VTE after RARP might not be so high and uniform prophylaxis might not be suitable for RARP because it might be the same as that after transurethral resection for bladder tumors. However, neoadjuvant ADT, high D-dimer levels after surgery and lymphocele formation should be noted as risk factors of VTE after RARP.
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