市川 智彦

INTRODUCTION: Maintaining a castration level of testosterone (TST) during radiation therapy combined with androgen deprivation therapy (ADT) is an essential strategy in the treatment of prostate cancer; however, hypogonadism can cause various complications. The aim was to compare serum TST recovery between LHRH agonists and LHRH antagonists. METHODS: A total of 131 patients who underwent radiation therapy with ADT for prostate cancer were retrospectively analyzed. Serum TST levels after termination of ADT including LHRH agonists and antagonists were compared. Cox proportional hazards model and the Kaplan-Meier method were used for statistical analysis. RESULTS: Median age, baseline TST, nadir TST, and duration of ADT were 71 years, 535 ng/dL, 10.92 ng/dL, and 12 months, respectively. Multivariate analysis identified significant associations of initial PSA ≥ 10.92 ng/mL (p = 0.0366), ADT ≥ 360 days (p = 0.0408), nadir TST ≤ 19 ng/dL (p = 0.0003), and LHRH agonist (p = 0.0027) with delayed TST recovery to castration level (50 ng/dL). We created a risk model based on these four independent risk factors (Low: 0-1 factor/Intermediate: 2 factors/High Risk: 3-4 factors). Each risk group significantly differentiated the TST recovery to castration level. Even after propensity score matching, recovery of TST to castration level and therapeutic level (200 ng/dL) was significantly delayed in the LHRH agonist group compared with the LHRH antagonist group (p = 0.0016, p = 0.0389, respectively). CONCLUSION: LHRH antagonists restored serum TST to castration and therapeutic levels faster than LHRH agonists in prostate cancer patients undergoing radiation therapy with ADT.

BACKGROUND: Clinical significance of primary tumor progression in patients with metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. METHODS: Clinical data from 987 patients with mHSPC from multiple institutions between September 1999 and November 2023 were reviewed. The prognostic impact of primary tumor progression was examined along with other clinical parameters. Castration-resistant prostate cancer progression-free survival (CRPC PFS) and overall survival (OS) were analyzed as clinical outcomes. Student's t-test, Cox proportional hazards models, and Kaplan-Meier methods were utilized to validate the clinical significance. RESULTS: The median age and initial prostate-specific antigen (iPSA) values were 74 and 221 ng/ml, respectively. 632 (64%) and 355 (36%) patients had clinical T stage ≤3 and 4 at diagnosis, respectively. mHSPC patients with clinical T stage 4 were more likely to have a higher grade group (GG), higher frequency of lymph node metastasis, lower hemoglobin (Hb), and more high-volume/risk disease in comparison with those with clinical T stage ≤3. Patients with cT4 were associated with shorter CRPC PFS (P=0.0002) and OS (P < 0.0001). Multivariate analysis identified cT4 as an independent prognostic factor for OS (HR=1.33, P=0.03) along with age, GG, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), albumin (Alb), and high-volume disease. After propensity score matching, patients with cT4 had unfavorable OS in comparison with those with ≤cT3 (P=0.0279). Furthermore, when combined with tumor volume, men with low-volume + cT4 achieved a prognosis comparable to that of patients with high-volume+≤cT3 and high-volume + cT4 (P=0.6876 and P=0.1679, respectively). CONCLUSION: Bulkiness of primary prostate tumor was associated with worse outcomes in patients with mHSPC. Men with cT4 will require multimodal and intensive therapeutic strategies irrespective of tumor volume.

Background: The aim of this study was to develop nomograms predicting 5- and 7-year biochemical-recurrence (BCR)-free survival in high-risk prostate cancer (PCa) patients treated with carbon-ion radiotherapy (CIRT) and androgen deprivation therapy (ADT). Methods: We retrospectively evaluated 785 high-risk PCa patients treated with CIRT and ADT. Based on the least absolute shrinkage and selection operator model, two nomograms predicting 5- and 7-year BCR-free survival were developed and internally validated. The ability of each nomogram to predict BCR-free survival was determined by calculating the area under the survival curve (AUC). Results: The 5- and 7-year BCR-free survival rates were 92.1% and 89.3%, respectively. Age, prostate-specific antigen level, clinical T stage, and Gleason score were incorporated into the nomogram predicting 5-year BCR-free survival. In addition to these variables, the percentage of positive biopsy cores was also added to the nomogram predicting 7-year BCR-free survival. The AUC value of each nomogram showed suboptimal-to-good discrimination. Conclusions: We developed the first nomograms accurately predicting BCR-free survival in high-risk PCa patients treated with CIRT and ADT. These nomograms will enable adequate understanding and explanation of BCR-free survival to patients when clinicians use them.

BACKGROUND: Recent clinical trials have shown that patients with metastatic castration-sensitive prostate cancer in real-world settings have different overall survival (OS) rates after stratifying for tumor burden or visceral metastasis. However, some patients with a low tumor burden and without visceral metastasis still have a poor survival. Androgen receptor signaling is still a main therapeutic target of prostate cancer treatment even after the achievement of castration resistance. In this regard, we hypothesized that time to castration resistance can be a prognostic factor of metastatic castration-sensitive prostate cancer even after achieving castration resistance. The current study aimed to assess the novel prognostic factors, particularly time to castration resistance, of prostate cancer in patients at a real-world single institution. METHODS: The data of 261 patients who were newly diagnosed with metastatic castration-sensitive prostate cancer from January 2007 to December 2023 were retrospectively analyzed. RESULTS: The median OS was 60.7 months, and the median time to castration resistance was 13.1 months. Among 261 patients, 158 developed castration-resistant prostate cancer. A shorter time to castration resistance, the presence of distant lymph node metastasis, ISUP grade group 5, and older age were associated with a shorter OS in patients who developed castration-resistant prostate cancer. A shorter time to castration resistance was significantly associated with a shorter OS regardless of the tumor burden. Further, it was associated with a shorter OS even after the achievement of castration resistance. CONCLUSIONS: The study results support the presence of persistent androgen receptor signaling even after achieving castration resistance in prostate cancer, and time to castration resistance can be a biomarker for the activation of androgen receptor signaling regardless of tumor burden.