金坂 学斗

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: This study investigated the characteristics of prostate-specific antigen (PSA) dynamics when androgen receptor signaling inhibitor (ARSI), or vintage agent (bicalutamide) was used for patients with metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: A total of 213 mHSPC patients from each of the ARSI and bicalutamide groups treated between 2015 and 2022 were selected from multiple institutions using propensity score-matched analysis to align backgrounds. PSA progression-free survival (PFS) and overall survival (OS) were assessed. PSA level at 3 months, PSA nadir level, and time to PSA nadir were examined to analyze of PSA kinetics. RESULTS: ARSI treatment significantly improved PSA PFS compared to bicalutamide (P = 0.0063), although no significant difference in OS was seen (P = 0.3134). No significant differences were observed between treatment groups in median PSA levels at 3 months (1.47 vs 0.52 ng/ml, P = 0.3042) or PSA nadir levels (0.263 vs 0.1345 ng/ml, P = 0.1228). Bicalutamide treatment demonstrated longer time to nadir than ARSI in progression-free cases (median: 243 vs 213.5 days, P = 0.0003). Survival tree analysis found that PSA nadir ≤ 1.5 ng/ml and time to nadir ≥ 145 days were the optimal cut-offs for best stratifying OS with bicalutamide, while PSA nadir ≤ 0.45 ng/ml and time to nadir ≥ 70 days were optimal with ARSI. CONCLUSION: No significant differences in PSA response was seen between groups; however, distinct optimal cut-offs were demonstrated for PSA nadir and time to nadir. The present findings will be useful for optimal PSA monitoring for mHSPC patients and for early identification of poor-prognosis populations.

OBJECTIVES: Renal cell carcinoma (RCC) is shown to have a tendency for late recurrence, occurring 5 or more years after curative surgery. Imaging diagnosis is required for follow-up, and there is no definitive answer as to how long this should continue. Some patients discontinue follow-up visits at their own discretion. How best to predict late recurrence and loss to follow-up (LF) remains unclear. PATIENTS AND METHODS: This study targeted patients diagnosed with non-metastatic RCC who underwent either radical or partial nephrectomy at Chiba University Hospital between 1988 and 2021. Follow-up for patients with RCC is typically lifelong. We used random survival forests (RSFs), a machine learning-based survival analysis method, to predict late recurrence and LF. For verification of prediction accuracy, we applied the time-dependent area under the receiver operating characteristic curve (t-AUC). To analyse the risks of late recurrence and LF, SurvSHAP(t) and partial dependence plots were used. RESULTS: We analysed 1051 cases in this study. Median follow-up was 58.5 (range: 0-376) months. The predictive accuracy of recurrence using RSF was t-AUC 0.806, 0.761, 0.674 and 0.566 at 60, 120, 180 and 240 months postoperatively, respectively. The recurrence risk impact showed a time-dependent increase up to approximately 50 months postoperatively. Beyond 50 months, there were no distinct risk factors characteristic of late recurrence. The predictive accuracy of LF using RSF was t-AUC 0.542, 0.699, 0.685, 0.628 and 0.674 at 60, 120, 180, 240 and 300 months postoperatively, respectively. The risk of LF increased with advancing age beyond 70 years. CONCLUSION: It is difficult to identify factors that predict late recurrence. For long-term follow-up observation, it is essential to pay particular attention to patients with RCC aged 70 years and above. Establishing frameworks to facilitate collaboration with local hospitals near patients' residences and providing care within the community is necessary.