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Objectives: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD). Methods: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance‐free survival (CRFS), metastasis‐free survival (MFS), cancer‐specific survival (CSS), and overall survival (OS). Results: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS. Conclusions: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2‐mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Background: This study is part of the SNPs in Nivolumab PD‐1 inhibitor for RCC (SNiP‐RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. Methods: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression‐free survival (PFS), overall survival (OS), and treatment‐related grade ≥ 3 (serious adverse events [SAEs]). Results: We included 222 patients. The median age was 69 years (interquartile range 62–74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. Conclusion: The SNiP‐RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy. [ABSTRACT FROM AUTHOR]

Objective: Novel androgen receptor axis‐targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs. Methods: We previously performed a multicenter study to identify prognostic factors for metastatic hormone‐sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3‐year OS (PROSTAT‐BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group. Results: The predictors were age (<71.4 years), serum levels of C‐reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not. Conclusions: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high‐risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs. [ABSTRACT FROM AUTHOR]

Objective: To determine prognostic factors including the Bone Scan Index in prostate cancer patients receiving standard hormonal therapy and chemotherapy. Methods: This multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index study involved 30 hospitals and enrolled 247 patients (age 71 ± 8 years) with metastatic hormone‐sensitive prostate cancer (n = 148) under hormone therapy and metastatic castration‐resistant prostate cancer (n = 99) under chemotherapy. The Bone Scan Index (%) was determined by whole‐body bone scintigraphy using 99mTc‐methylenediphosphonate. Patients were classified into tertiles and binary groups, and predictors of all‐cause death including Bone Scan Index, prostate‐specific antigen, and bone metabolic markers were determined using survival and proportional hazard analyses. Results: During a mean follow‐up period of 716 ± 404 days, 81 (33%) of the patients died, and 3‐year mortality rates were 20% and 52% in the metastatic hormone‐sensitive prostate cancer and metastatic castration‐resistant prostate cancer groups, respectively. Survival analysis showed that a Bone Scan Index >3.5% was a significant determinant of death in the metastatic hormone‐sensitive prostate cancer group, whereas prostate‐specific antigen >55 ng/mL before chemotherapy was a determinant of prognosis in the metastatic castration‐resistant prostate cancer group. A Bone Scan Index >3.5% was also associated with a high incidence of prostate‐specific antigen progression in the metastatic hormone‐sensitive prostate cancer group. Patients with metastatic hormone‐sensitive prostate cancer and a better Bone Scan Index response (>45%) to treatment had lower mortality rates than those without such response. Conclusion: The Bone Scan Index and hot spot number are significant determinants of 3‐year mortality, and combining the Bone Scan Index with prostate‐specific antigen should contribute to the management of prostate cancer patients with bone metastasis. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusion To report the outcomes of repeat biopsies, metastasis and survival in the Prostate Cancer Research International: Active Surveillance (PRIAS)‐JAPAN study, a prospective observational study for Japanese patients, initiated in 2010.At the beginning, inclusion criteria were initially low‐risk patients, prostate‐specific antigen (PSA) density (PSAD) <0.2, and ≤2 positive biopsy cores. As from 2014, GS3+4 has also been allowed for patients aged 70 years and over. Since January 2021, the age limit for Gleason score (GS) 3 + 4 cases was removed, and eligibility criteria were expanded to PSA ≤20 ng/mL, PSAD <0.25 nd/mL/cc, unlimited number of positive GS 3 + 3 cores, and positive results for fewer than half of the total number of cores for GS 3 + 4 cases if magnetic resonance imaging fusion biopsy was performed at study enrolment or subsequent follow‐up. For patients eligible for active surveillance, PSA tests were performed every 3 months, rectal examination every 6 months, and biopsies at 1, 4, 7 and 10 years, followed by every 5 years thereafter. Patients with confirmed pathological reclassification were recommended for secondary treatments.As of February 2024, 1302 patients were enrolled in AS; 1274 (98%) met the eligibility criteria. The median (interquartile range) age, PSA level, PSAD, and number of positive cores were 69 (64–73) years, 5.3 (4.5–6.6) ng/mL, 0.15 (0.12–0.17) ng/mL, and 1 (1–2), respectively. The clinical stage was T1c in 1089 patients (86%) and T2 in 185 (15%). The rates of acceptance by patients for the first, second, third and fourth re‐biopsies were 83%, 64%, 41% and 22%, respectively. The pathological reclassification rates for the first, second, third and fourth re‐biopsies were 29%, 30%, 35% and 25%, respectively. The 1‐, 5‐ and 10‐year persistence rates were 77%, 45% and 23%, respectively. Six patients developed metastasis, and one patient died from prostate cancer.Pathological reclassification was observed in approximately 30% of the patients during biopsy; however, biopsy acceptance rates decreased over time. Although metastasis occurred in six patients, only one death from prostate cancer was recorded. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p = 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p = 0.024) and improving cancer-specific survival compared with the low group (p = 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC., (Copyright © 2024 by The American Association of Immunologists, Inc.)

The present study aimed to evaluate the optimal timing of radium-223 chloride (Ra-223) administration among patients with bone metastasis from castration-resistant prostate cancer (BmCRPC). Patients, who were diagnosed with BmCRPC and treated with Ra-223 therapy between October, 2016 and January, 2022, were reviewed. The survival time was calculated from the initiation of Ra-223 administration. The time from the diagnosis of BmCRPC to the initiation of Ra-223 administration was identified as a potential prognostic factor. A total of 51 patients were examined in the present study. Ra-223 was administered as the first- and second-line therapy (earlier Ra-223 administration) in 32 patients and as the third- to fifth-line therapy (later Ra-223 administration) in 19 patients. In the multivariate analysis, which considered the potential prognosis, the difference in survival times between patients who received early and late Ra-223 administration was not significant [hazard ratio (HR), 2.67; 95% confidence interval (CI), 0.79-9.07; P=0.11]. By contrast, an incomplete Ra-223 administration (HR, 128.03; 95% CI, 10.59-1548.42; P<0.01) and higher levels of prostate-specific antigen prior to Ra-223 administration (HR, 7.86; 95% CI, 2.7-27.24; P<0.01) were independent factors, significantly associated with a poorer prognosis. The timing of Ra-223 administration did not significantly affect the survival of patients from the initiation of treatment. Further studies are thus required to determine the optimal timing for Ra-223 administration., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Makita et al.)