Current Status of Prostate-specific Membrane Antigen-targeted Alpha Radioligand Therapy in Prostate Cancer.

Prostate cancer (PCa) is the most prevalent malignancy and leading cause of mortality in men. Despite the development of various drugs, such as novel androgen receptor signaling inhibitors and poly adenosine diphosphate-ribose polymerase inhibitors targeting homologous recombination repair-related genetic mutations, prognosis of metastatic castration-resistant prostate cancer remains unfavorable. However, recent advances in nuclear medicine have allowed for both imaging diagnostics and therapeutic interventions by targeting molecules specifically expressed in cancer cells with radioisotopes (RI). γ-rays are used in nuclear medicine imaging, whereas in therapy, α or ß-emitting RIs are administered to target cells in radiation therapy. PCa, in particular, exhibits the characteristic features of radioligand therapy, as the membrane protein prostate-specific membrane antigen (PSMA) is proportionally highly expressed in malignancy compared to normal tissues. The administered RI-labeled compound binds to PSMA, enabling specific targeting of PCa for treatment. Unlike ß-rays, α-rays have a shorter range and impart stronger energy to DNA, allowing α-particles to exhibit a higher linear energy transfer. Due to such characteristics, PSMA-targeted α radiotherapy is expected to have potent cytotoxic effects and fewer side effects on normal organs, making them more likely to be widely adopted in the future. However, reports on PSMA-targeted α radiotherapy differ in aspects, such as prior PSMA-targeted ß radiotherapy, the administered doses, and the number of treatment cycles. Therefore, in this review, we compile the reports on treatments utilizing α-emitting isotopes targeting PSMA in patients with PCa.

Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management.

Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear. We aimed to determine the cumulative incidence and risk factors of MRONJ. One hundred and seventy-nine patients with prostate cancer with bone metastases treated with BMA at our institution since 2008 were included in this study. Twenty-seven patients (15%) had MRONJ during the follow-up period (median, 19 months; interquartile range, 9-43 months). The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93-11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01-0.64). Furthermore, six or more bone metastases (HR 3.65, 95% CI 1.13-11.7) and diabetes mellitus (HR 5.07, 95% CI 1.68-15.2) were risk factors for stage 2 or more severe MRONJ. MRONJ should be considered during long-term BMA administration in prostate cancer patients with bone metastases.

Impact of prior abdominal surgery on the outcomes after robotic - assisted laparoscopic radical prostatectomy: single center experience

ABSTRACT Purpose: To evaluate the influence of prior abdominal surgery on the outcomes after robotic-assisted laparoscopic radical prostatectomy (RALP). Materials and Methods: We retrospectively analyzed patients with prostate cancer who underwent RALP between June 2012 and February 2015 at our institution. Patients with prior abdominal surgery were compared with those without prior surgery while considering the mean total operating, console, and port-insertion times; mean estimated blood loss; positive surgical margin rate; mean duration of catheterization; and rate of complications. Results: A total of 203 patients who underwent RALP during the study period were included in this study. In all, 65 patients (32%) had a prior history of abdominal surgery, whereas 138 patients (68%) had no prior history. The total operating, console, and port-insertion times were 328 and 308 (P=0.06), 252 and 242 (P=0.28), and 22 and 17 minutes (P=0.01), respectively, for patients with prior and no prior surgery. The estimated blood losses, positive surgical margin rates, mean durations of catheterization, and complication rates were 197 and 170 mL (P=0.29), 26.2% and 20.2% (P=0.32), 7.1 and 6.8 days (P=0.74), and 12.3% and 8.7% (P=0.42), respectively. Furthermore, whether prior abdominal surgery was performed above or below the umbilicus or whether single or multiple surgeries were performed did not further affect the perioperative outcomes. Conclusions: Our results suggest that RALP can be performed safely in patients with prior abdominal surgery, without increasing the risk of complications.