Population pharmacokinetics and pharmacodynamic target attainment analysis of cefazolin using total and unbound serum concentration in patients with prostatectomy or nephrectomy.

The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC90, 0.5 mg/L, and MIC50, and 1.0 mg/L, to account for methicillin-susceptible Staphylococcus aureus (MSSA) or Escherichia coli. Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC50 for E. coli or MIC90 for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals.

Real-world data on the comprehensive genetic profiling test for Japanese patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: comprehensive genomic profiling test has been covered by Japanese health insurance since June 2019. However, no real-world data on the test have been reported with a focus on Japanese patients with prostate cancer. METHODS: we retrospectively reviewed the data of 45 consecutive patients with metastatic castration-resistant prostate cancer, who underwent the comprehensive genomic profiling tests at Kitasato University Hospital between August 2019 and December 2022. Patients' characteristics, prevalence of gene alterations and therapeutic impact of genotype-matched therapy were assessed. RESULTS: genomic data were obtained using a tissue-based test (n = 32) and liquid-based test (n = 13). Actionable genomic alternations were identified in 51.1% of patients, and 22.2% were treated with genotype-matched therapy. The main reason for not receiving genotype-matched therapy was disease progression, accounting for 46.2% (6/13). Kaplan-Meier analysis showed significantly longer overall survival after the comprehensive genomic profiling tests in patients with genotype-matched therapy under public insurance (17.8%, n = 8) than those without it (median: not reached vs. 18.1 months; P = 0.003). Five (62.5%) out of the eight patients with genotype-matched therapy under public insurance had BRCA1 or 2 deleterious alteration. Multivariate analyses showed that BRCA deleterious alteration (17.8%, n = 8) was an independent risk factor for shorter time to castration-resistant prostate cancer (hazard ratio: 2.46, 95% confidence interval: 1.04-5.87; P = 0.041), and no patients with the alteration had ≤5 bone metastases. CONCLUSIONS: the results of this study showed the promising survival outcomes in patients with genotype-matched therapy under public insurance, even in the castration-resistant prostate cancer setting. Further detection of promising therapeutic target gene is expected to increase the number of patients who reach genotype-matched therapies.

Membranous Expression of Heart Development Protein with EGF-like Domain 1 Is Associated with a Good Prognosis in Patients with Bladder Cancer.

OBJECTIVE: To investigate the correlation between total protein expression of heart development protein with EGF-like domain 1 (HEG1) and clinicopathological characteristics in patients with bladder cancer (BC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analyzed data from 110 patients who underwent RC at Kitasato University Hospital. And we prepared an anti-HEG1 monoclonal antibody W10B9, which can detect total HEG1 protein. HEG1 protein expression in tumor cells was evaluated separately for membrane and cytoplasmic staining using immunohistochemistry. RESULTS: Membranous HEG1 expression was associated with absent lymphovascular invasion (p < 0.01) and low pT stage (p < 0.01). Kaplan-Meier analysis revealed that the membranous HEG1-positive group had significantly long recurrence-free survival (RFS) (p < 0.01) and cancer-specific survival (p = 0.01). Expression of membranous HEG1 was identified as an independent prognostic factor for RFS (p = 0.04). There were no significant differences between cytoplasmic HEG1 expression and clinicopathologic factors including prognosis. CONCLUSION: The expression of membranous HEG1 could serve as a favorable prognostic indicator in patients with BC treated with RC.

Dosimetric Predictors of Toxicity after Prostate Stereotactic Body Radiotherapy: A Single-Institutional Experience of 145 Patients.

The indications for stereotactic body radiotherapy (SBRT) for prostate cancer have increased. However, the relationships between adverse events and risk factors remain unclear. This study aimed to clarify associations between adverse events and dose index for prostate SBRT. Participants comprised 145 patients irradiated with 32-36 Gy in 4 fractions. Radiotherapy-related risk factors such as dose-volume histogram parameters and patient-related risk factors such as T stage and Gleason score were evaluated in a competing risk analysis. Median follow-up duration was 42.9 months. A total of 9.7% had acute Grade ≥ 2 GU toxicities and 4.8% had acute Grade ≥ 2 GI toxicities. A total of 11.1% had late Grade ≥ 2 GU toxicities and 7.6% had late Grade ≥ 2 GI toxicities. Two (1.4%) patients suffered from late Grade 3 GU toxicities. Similarly, two (1.4%) patients suffered from late Grade 3 GI toxicities. Acute GU and GI events correlated with prostate volume and dose to the hottest 10 cc volume (D10cc)/volumes receiving a minimum of 30 Gy (V30 Gy) of rectum, respectively. Late GI toxicity, frequency, and rectal hemorrhage correlated with rectal D0.1 cc/D1 cc, maximum dose to the bladder, and rectal D0.1 cc, respectively. Toxicities after prostate SBRT using 32-36 Gy/4 fractions were acceptable. Our analysis showed that acute toxicities correlated with volume receiving a medium dose level, and late toxicities correlated with highest point dose of organs at risk.

Development and validation of a survival nomogram and calculator for male patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate and/or enzalutamide.

BACKGROUND: Despite the widespread availability of medication choices for metastatic castration-resistant prostate cancer (mCRPC), biomarkers to predict the efficacy of each mCRPC treatment have not yet been established. This study developed a prognostic nomogram and a calculator to predict the prognosis of patients with mCRPC who received abiraterone acetate (ABI) and/or enzalutamide (ENZ). METHODS: In total, 568 patients with mCRPC who underwent ABI and/or ENZ between 2012 and 2017 were enrolled. A prognostic nomogram based on the risk factors was developed using the Cox proportional hazards regression model and clinically important factors. The discriminatory ability of the nomogram was assessed according to the concordance index (C-index). A 5-fold cross-validation was repeated 2000 times to estimate the C-index, and the means of the estimated C-index for the training and validation sets were determined. A calculator based on this nomogram was then developed. RESULTS: The median overall survival (OS) was 24.7 months. Multivariate analysis showed that the time to CRPC, pre-chemotherapy, baseline prostate-specific antigen, baseline alkaline phosphatase, and baseline lactate dehydrogenase levels were independent risk factors for OS (hazard ratio [HR]: 0.521, 1.681, 1.439, 1.827, and 12.123, p = 0.001, 0.001, < 0.001, 0.019, and < 0.001, respectively). The C-index was 0.72 in the training cohort and 0.71 in the validation cohort. CONCLUSIONS: We developed a nomogram and calculator to predict OS in Japanese patients with mCRPC who received ABI and/or ENZ. Reproducible prognostic prediction calculators for mCRPC will facilitate greater accessibility for clinical use.

[Clinical Outcome of Microsatellite Instability-High Patients Treated with Pembrolizumab and Genetic Counseling].

Prospective studies have demonstrated the efficacy of pembrolizumab in patients with previously treated unresectable or metastatic microsatellite instability-high(MSI-H)cancers. Pembrolizumab has been covered by the Japanese health insurance system since December 2018. The frequency of MSI-H in patients is as low as approximately 2%. In addition, some patients with MSI-H cancers are diagnosed with Lynch syndrome. In the present study, we retrospectively investigated patients who received MSI testing at Kitasato University Hospital from April 2019 to June 2020. We also investigated the therapeutic effect of pembrolizumab for MSI-H cancers and patients who received genetic counseling for Lynch syndrome. Results identified that 5 out of 263 patients who underwent MSI testing(1.9%)had MSI-H. The therapeutic outcomes of pembrolizumab in those patients were as follows: 1(20%)complete response, 3(60%)partial response, and 1(20%) progressive disease. The positive-outcome rate of MSI-H treatment in our institution was comparable to that in the previous reports. The high response rate of pembrolizumab was confirmed in the present study. Four out of 5 patients received genetic counseling at the genetic clinic, and 1 patient underwent genetic testing for Lynch syndrome. No deleterious variant of Lynch syndrome was detected in the genetic testing.

Comparative effectiveness of low-dose-rate brachytherapy with or without external beam radiotherapy in favorable and unfavorable intermediate-risk prostate cancer.

We compared clinical outcomes associated with seed brachytherapy (SEED-BT) alone and SEED-BT plus external-beam radiotherapy (EBRT) for intermediate-risk prostate cancer using propensity score-matched analysis. From 2006 to 2011, 993 patients diagnosed with intermediate-risk were treated with either SEED-BT alone (n = 775) or SEED-BT plus EBRT (n = 158) at 3 tertiary hospitals. In the propensity score-matched analysis (102 pairs), median follow-up was 95 months (range 18-153 months). The 8-year biochemical recurrence-free rate (bRFR) was significantly better with SEED-BT alone than with combined radiotherapy (93.3% vs. 88.4%; HR 0.396; 95% CI 0.158-0.991). Grade 2 or greater late genitourinary toxicities were significantly fewer with SEED-BT alone than with combined radiotherapy (21.0% vs. 33.2%; HR 0.521; 95% CI 0.308-0.881). Similarly, grade 2 or greater late gastrointestinal toxicities were significantly fewer with SEED-BT alone (0% vs. 12.2%; HR 0.125; 95% CI 0.040-0.390). For the unfavorable intermediate-risk subgroups, SEED-BT alone yielded a significantly better bRFR than the combined radiotherapy (HR 0.325; 95% CI 0.115-0.915). SEED-BT alone might be a better disease-management plan than SEED-BT plus EBRT for intermediate-risk prostate cancer regardless of favorable and unfavorable characteristics.

Direct comparison of low-dose-rate brachytherapy versus radical prostatectomy using the surgical definition of biochemical recurrence for patients with intermediate-risk prostate cancer.

BACKGROUND: We compared the oncological outcomes of patients who received seed brachytherapy (SEED-BT) with those who received radical prostatectomy (RP) for intermediate-risk prostate cancer. METHODS: Candidates were patients treated with either SEED-BT (n = 933) or RP (n = 334). One-to-one propensity score matching was performed to adjust the patients' backgrounds. We compared the biochemical recurrence (BCR)-free rate using the Phoenix definition (prostate-specific antigen [PSA] nadir plus 2 ng/mL) for SEED-BT and the surgical definition (PSA cut-off value of 0.2 ng/mL) for RP. We also directly compared the BCR-free rates using the same PSA cut-off value of 0.2 ng/mL for both SEED-BT and RP. RESULTS: In the propensity score-matched analysis with 214 pairs, the median follow-up treatment was 96 months (range 1-158 months). Fifty-three patients (24.7%) were treated with combined SEED-BT and external-beam radiotherapy. Forty-three patients (20.0%) received salvage radiotherapy after RP. Comparing the BCR-free rate using the above definitions for SEED-BT and RP showed that SEED-BT yielded a significantly better 8-year BCR-free rate than did RP (87.4% vs. 74.3%, hazard ratio [HR] 0.420, 95% confidence interval [CI] 0.273-0.647). Comparing the 8-year BCR-free rate using the surgical definition for both treatments showed no significant difference between the two treatments (76.7% vs. 74.3%, HR 0.913, 95% CI 0.621-1.341). SEED-BT had a significantly better 8-year salvage hormonal therapy-free rate than did RP (92.0% vs. 85.6%, HR 0.528, 95% CI 0.296-0.942, P = 0.030). The 8-year metastasis-free survival rates (98.5% vs. 99.0%, HR 1.382, 95% CI 0.313-6.083, P = 0.668) and overall survival rates (91.9% vs. 94.6%, HR 1.353, 95% CI 0.690-2.650) did not significantly differ between the treatments. CONCLUSIONS: The BCR-free rates did not significantly differ between patients treated with SEED-BT and those treated with RP for intermediate-risk prostate cancer even when they were directly compared using the surgical definition for BCR. SEED-BT and RP can be adequately compared for oncological outcomes.

Cytopathic effects and local immune responses in repeated neoadjuvant HSV-tk + ganciclovir gene therapy for prostate cancer.

OBJECTIVE: Cytopathic effects and local immune response were analyzed histologically in prostatic cancer (PCa) with in situ herpes simplex virus-thymidine kinase (HSV-tk)/ganciclovir (GCV) gene therapy (GT). METHODS: Four high-risk PCa patients who received HSV-tk/GCV GT were investigated. After two cycles of intraprostatic injection of HSV-tk and administration of GCV, radical prostatectomy was performed. Formalin-fixed, paraffin-embedded sections were evaluated using immunohistochemistry. PCa with hormone therapy (HT, n=3) or without neoadjuvant therapy (NT, n=4) that were equivalent in terms of risk were also examined as reference. Immunoreactively-positive cells were counted in at least three areas in cancer tissue. Labeling indices (LI) were calculated as percentage values. RESULTS: ssDNA LI in GT increased, indicating apoptosis, as well as tumor-infiltrating lymphocytes and CD68-positive macrophages, compared with their biopsies. GT cases showed significantly higher numbers of single-stranded DNA (ssDNA) LI, CD4/CD8-positive T cells and CD68-positive macrophages including M1/M2 macrophages than HT or NT cases. However, there was no significant difference in CD20-positive B cells among the types of case. There were strong correlations between CD8+ T cells and CD68+ macrophages (ρ=0.656, p<0.0001) as well as CD4+ T cells and CD20+ B cells (ρ=0.644, p<0.0001) in PCa with GT. CONCLUSIONS: Enhanced cytopathic effect and local immune response might be indicated in PCa patients with HSV-tk/GCV gene therapy.

[Clinicopathological Characteristics of Adolescent and Young-Adult Patients with Bladder Cancer].

Bladder cancer is extremely rare in young patients. We reported the clinicopathological outcomes in adolescent and young adult patients with bladder cancer, using age 35 as the cut-off. From 1972 to 2011, 1349 patients were treated with transurethral resection of bladder tumor. Thirty patients were ＜35 years of age and were divided into two groups : ＜30 and ≧30 years. We reviewed the initial symptoms, cystoscopic and pathological findings, and prognosis. Thirteen patients (0.96%) were ＜30 years of age and seventeen (1.3%) were ≧30 of age, with mean follow-up periods of 88.2 and 77.6 months, respectively. The most common complaint was gross hematuria. Most tumors were solitary (26 ; 86.7%) and papillary (29 ; 96.7%). Pathological stages were pTa 15, pT1 10, and pT2 3. Patients with pT2 cancer were ≧30 years of age (p ＝ 0.019). One patient died of bladder cancer. The majority of patients had low-grade, low pathological stage bladder cancer and a good prognosis. However, some pT2 cancers exhibited aggressive behavior.

Effect of cisplatin on metastatic castration-resistant prostate cancer with BRCA2 mutation: A case report.

Poly (ADP-ribose) polymerase inhibitors exhibit strong activity for treating the DNA damage repair defect in patients with prostate carcinoma (PCa). Although conventional DNA-damaging agents can theoretically lead to synthetic antitumoral effects, no report has clearly mentioned the clinical use of cisplatin for treating PCa patients with the breast cancer gene (BRCA)2 mutation. We administered 80 mg/m2 cisplatin triweekly to a patient with metastatic castration-resistant PCa (mCRPC) with the BRCA2 mutation, and after ten cycles, the prostate-specific antigen was dramatically decreased. We suggest that BRCA2 mutations may indicate the use of cisplatin for treating patients with mCRPC.

Multi-institutional retrospective analysis of ultrahypofractionated radiotherapy for Japanese prostate cancer patients.

To report outcomes and risk factors of ultrahypofractionated (UHF) radiotherapy for Japanese prostate cancer patients. This multi-institutional retrospective analysis comprised 259 patients with localized prostate cancer from 6 hospitals. A total dose of 35-36 Gy in 4-5 fractions was prescribed for sequential or alternate-day administration. Biochemical failure was defined according to the Phoenix ASTRO consensus. Toxicities were assessed using National Cancer Institute Common Toxicity Criteria version 4. Tumor control and toxicity rates were analyzed by competing risk frames. Median follow-up duration was 32 months (range 22-97 months). 2- and 3-year biochemical control rates were 97.7% and 96.4%, respectively. Initial prostate-specific antigen (p < 0.01) and neoadjuvant androgen deprivation therapy (p < 0.05) were identified as risk factors for biochemical recurrence. 2- and 3-year cumulative ≥ Grade 2 late genitourinary (GU) toxicities were 5.8% and 7.4%, respectively. Corresponding rates of gastrointestinal (GI) toxicities were 3.9% and 4.5%, respectively. Grade 3 rates were lower than 1% for both GU and GI toxicities. No grade 4 or higher toxicities were encountered. Biologically effective dose was identified as a risk factor for ≥ Grade 2 late GU and GI toxicities (p < 0.05). UHF radiotherapy offered effective, safe treatment for Japanese prostate cancer with short-term follow-up. Our result suggest higher prescribed doses are related to higher toxicity rates.

A novel prognostic model for Japanese patients with newly diagnosed bone-metastatic hormone-naïve prostate cancer.

Objectives: To evaluate the prognosis of newly diagnosed patients with metastatic hormone-naïve prostate cancer (mHNPC) and develop a novel prognostic model based on ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) risk classifications. Patients and methods: We retrospectively analyzed the data of 578 newly diagnosed mHNPC patients initially treated with androgen deprivation therapy. We evaluated three clinical factors, namely, CHAARTED risk classifications (high-volume disease [HVD] vs low-volume disease [LVD]), Gleason scores (GS, 9-10 vs ≤8), and hemoglobin (Hb, ≤13.0 g/dL vs >13.0 g/dL), for their prognostic potential in predicting time to castration-resistant prostate cancer (TTC) and overall survival (OS) of mHNPC patients by multivariate analysis. Moreover, we developed a novel prognostic model that consisted of significant prognostic factors. Results: Of the entire cohort, the median TTC and OS values were 18.3 and 67.5 months, respectively. HVD, GS 9-10, and Hb ≤13.0 g/dL were independent poor prognostic factors for both TTC and OS. We developed a novel prognostic model which could stratify mHNPC patients into four risk groups according to the numbers of poor prognostic factors: group 1, LVD with low-risk (LVD patients without GS 9-10 and Hb ≤13.0 g/dL); group 2, LVD with high-risk (LVD patients with GS 9-10, Hb ≤13.0 g/dL, or both); group 3, HVD with low-risk (HVD patients without GS 9-10 with or without Hb ≤13.0 g/dL); and group 4, HVD with high-risk (HVD patients with GS 9-10 with or without Hb ≤13.0 g/dL). The median TTC and OS of groups 1, 2, 3, and 4 were 124.8, 36.4, 17.9, and 11.2 months, and 117.2, 94.2, 67.9, and 46.2 months, respectively. A significant difference in TCC and OS was found between all groups. Conclusion: We developed a prognostic model for mHNPC patients that consisted of CHAARTED risk classifications, GS, and Hb. Our prognostic model could significantly stratify the prognosis of patients with LVD and HVD into two groups each. This model might be a good reference for shared decision making between patients and physicians on the initial treatment for mHNPC.

High HNRNPA3 expression is associated with lymph node metastasis and poor prognosis in patients treated with radical cystectomy.

OBJECTIVE: We sought to identify heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) expression in bladder cancer and its relationship to clinicopathological findings and prognosis. METHODS: Immunohistochemical staining for HNRNPA3 was performed on 122 archived radical cystectomy specimens, with immunoreactivity being stratified on a 0 to 3 scale. The percentage of HNRNPA3 expressing tumor cells was calculated and multiplied by the staining score over an average of 5 areas to obtain a semiquantitative H-score (maximum value: 300). HNRNPA3 expression was categorized as high (≥80) or low (<80). RESULTS: The patients' median age was 70 years, and the median follow-up period was 39.4 months. High HNRNPA3 expression was significantly associated with lymph node metastasis (P= 0.014) and S100A8, S100A9 and uroplakin III expression (P= 0.028, 0.002, and 0.047, respectively). Log-rank tests indicated that high HNRNPA3 expression was significantly associated with disease progression and cancer-specific death (P= 0.013 and 0.006, respectively). In the Cox proportional hazards regression analysis, only lymph node metastasis was associated with disease progression and cancer-specific survival. CONCLUSION: HNRNPA3 may be a new biomarker to predict biologically aggressive cancers and determine the appropriate treatment modality in patients after radical cystectomy.

[In Situ Ductal Carcinoma with Hereditary Breast and Ovarian Cancer Syndrome in a Patient Who Received Contralateral Risk-Reducing Mastectomy-A Case Report].

A woman in her 30s presented to our hospital with the chief complaint of a right breast mass after the birth of her first child. She was diagnosed as having right invasive ductal carcinoma of Luminal-B type and T3N3cM0, stage Ⅲc. While undergoing neoadjuvant chemotherapy, she received genetic counseling and underwent genetic testing and was determined to have deleterious BRCA1 and BRCA2 mutations. After completing chemotherapy, she underwent a right total mastectomy and axillary lymph node dissection. Two years postoperatively, she requested to undergo a contralateral risk-reducing mastectomy( CRRM)of her left breast. Therefore, CT and breast MRI were performed to confirm the absence of contralateral lesions and distant metastases, and subsequently, CRRM was performed. Postoperative pathology results showed non-invasive ductal carcinoma lesions at 5 sites. In the case of hereditary breast and ovarian cancer syndrome such as in this study, lesions may be discovered at an early stage by performing risk-reducing mastectomy.

A high neutrophil-to-lymphocyte ratio is a poor prognostic factor for castration-resistant prostate cancer patients who undergo abiraterone acetate or enzalutamide treatment.

BACKGROUND: Inflammatory cytokine markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-lymphocyte ratio, and platelet-to-lymphocyte ratio, play important roles as prognostic markers in several solid malignancies, including prostate cancer. We previously reported the NLR as a poor prognostic marker in bladder cancer, upper-urothelial carcinoma, adrenocortical carcinoma, penile cancer, and prostate cancer. This study examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received abiraterone acetate or enzalutamide. METHODS: A total of 805 prostate cancer patients developed in CRPC status were enrolled in this study. Of these patients, 449 received abiraterone acetate (ABI; 188 cases) or enzalutamide (ENZ; 261 cases) treatment, and the pre-treatment NLR values of these patients were obtained. We investigated the prognosis in those with higher and lower NLR values. RESULTS: The median NLR was 2.90, and a receiver operating characteristics analysis suggested a candidate cut-off point of 3.02. The median overall survival (OS) was 17.3 months in the higher NLR group (≥3.02) and 27.3 months in the lower NLR group (< 3.02) (p < 0.0001). This trend was also observed in both the ABI and ENZ groups (ABI: 29.3 vs. 15.1 months; ENZ: NR vs. 19.5 months; p < 0.0001 and < 0.0001, respectively). A multivariate analysis revealed that a higher NLR was an independent risk factor. The NLR value was thus shown to be correlated with the prostate cancer progression. CONCLUSIONS: A higher NLR was associated with a poorer OS for CRPC patients who received ABI or ENZ. The NLR was positively correlated with prostate cancer progression.

Prognostic Value of the LATITUDE and CHAARTED Risk Criteria for Predicting the Survival of Men with Bone Metastatic Hormone-Naïve Prostate Cancer Treated with Combined Androgen Blockade Therapy: Real-World Data from a Japanese Multi-Institutional Study.

BACKGROUND: The CHAARTED and LATITUDE trials demonstrated a prolonged overall survival (OS) for metastatic hormone-naïve prostate cancer (mHNPC) patients who receive up-front docetaxel or abiraterone acetate. These studies used their own risk criteria: CHAARTED trial defines high- and low-volume diseases and LATITUDE trial targeting a high-risk disease. The present study explored whether or not the CHAARTED and LATITUDE criteria were useful for predicting the outcome in Japanese bone mHNPC patients, including elderly patients (≥70 years). METHODS: A total of 532 mHNPC patients diagnosed from 2004 to 2014 in multithird referral cancer centers were enrolled in this study. All patients had bone metastasis and received combined androgen blockade treatment as an initial hormonal therapy. RESULTS: The number of patients with CHAARTED low-volume and high-volume diseases was 178 (33.5%) and 354 (66.5%), respectively. On the contrary, the number of patients with LATITUDE low-risk and high-risk diseases was 157 (29.5%) and 375 (70.5%), respectively. A total of 307 (57.7%) patients were defined as having both CHAARTED high-volume and LATITUDE high-risk disease. The median castration-resistant prostate cancer- (CRPC-) free survival was 12.5 months for the CHAARTED high volume, 56.9 months for the CHAARTED low volume, 13.6 months for the LATITUDE high risk, and 37.3 months for the LATITUDE low risk, respectively. The OS was 50.1 months in patients with CHAARTED high-volume disease, 95.1 months in patients with CHAARTED low-volume disease, 54.0 months in patients with LATITUDE high-risk disease, and 92.7 months in patients with LATITUDE low-risk disease, respectively. This trend was also observed in elderly (≥70 years old) patients. CONCLUSIONS: The patients with CHAARTED high-volume disease or LATITUDE high-risk disease showed a shorter CRPC-free survival and a shorter OS than those in the CHAARTED low-volume disease group or in the LATITUDE low-risk group among Asian Japanese bone metastatic HNPC patients.

Size of pelvic bone metastasis as a significant prognostic factor for metastatic prostate cancer patients.

INTRODUCTION: To investigate the potential prognostic value of image analysis of pelvic bone metastasis in newly diagnosed prostate cancer patients. METHODS: Data from 69 patients with both bone scintigraphy and pelvic CT images were selected for this analysis. Open source software (3D Slicer version 4.8.1.) was used for image analysis. Metastatic pelvic bone lesions were manually contoured, and radiomic features were extracted. As risk factors for overall survival (OS) and cause-specific survival (CSS), 105 radiomic features and clinical risk factors including age, initial prostate-specific antigen, Gleason score, TNM stage, lactate dehydrogenase (LDH), hemoglobin (Hb), alkaline phosphatase, extent of disease, visceral metastases, and radiotherapy were assessed by uni- and multivariate analyses. RESULTS: Median follow-up was 41 months (range 0-157 months). Five-year overall survival and cause-specific survival rate were 37.9% and 43.5%, respectively. After multivariate analysis, LDH, Hb, and "maximum 2D diameter" defined as maximum tumor size in the axial plane were detected as risk factors for OS. Gleason sum, LDH, and maximum 2D diameter were detected as risk factors for CSS. CONCLUSION: Maximum 2D diameter was detected as a significant prognostic factor for metastatic prostate cancer patients.

[A Case of Retroperitoneal Mature Teratoma Successfully Treated by Laparoscopic Adrenalectomy].

We report a case of retroperitoneal mature teratoma which was successfully treated by laparoscopic adrenalectomy. A 37-year-old woman complaining of right abdominal discomfort was referred to our hospital because computed tomography showed an adrenal tumor at another hospital. Magnetic resonance imaging showed a 10 cm adrenal tumor that consisted of fat with calcification. Endocrine examination showed no abnormal findings. Under the suspicion of myelolipoma, we performed laparoscopic right adrenalectomy. Histological diagnosis was mature teratoma. The patient had no recurrence at 5 years after surgery.

Efficacy and safety of apalutamide in Japanese patients with nonmetastatic castration-resistant prostate cancer: a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase-3 study.

BACKGROUND: In the global Phase-3 Selective Prostate Androgen Receptor Targeting with ARN-509 study, apalutamide plus ongoing androgen deprivation therapy (ADT) significantly increased metastasis-free survival (MFS) and improved other clinical outcomes in men with nonmetastatic castration-resistant prostate cancer (nm-CRPC) who were at high risk of developing metastases. In this subpopulation analysis of Selective Prostate Androgen Receptor Targeting with ARN-509 study, the efficacy and safety of apalutamide plus ADT were evaluated in Japanese patients with nm-CRPC. METHODS: The primary efficacy end point was MFS. Secondary efficacy end points were time to metastasis, progression-free survival, symptomatic progression, initiation of cytotoxic chemotherapy, and overall survival. Safety and pharmacokinetic parameters were also assessed. RESULTS: Fifty-five Japanese patients with ongoing ADT were randomized (apalutamide: n = 34, placebo: n = 21). Median treatment duration was 5.7 months in the apalutamide group and 11.0 months in the placebo group. Median MFS was not reached in the apalutamide group (95% confidence interval: 10.97, not estimable) and was 18.23 months (95% confidence interval: 11.04, 18.50) in the placebo group. Secondary end points were improved in the apalutamide group. The safety profile of apalutamide with ADT was comparable with the global population, and no new safety signals were identified in this Japanese subpopulation. Although, apalutamide exposure tended to be higher in the Japanese subpopulation compared with the non-Japanese population, this was likely to be explained by body weight and considered not clinically meaningful. CONCLUSION: In the Japanese subpopulation, treatment with apalutamide with ADT resulted in favorable efficacy outcomes with comparable benefit-risk profile to the global population with nm-CRPC who are at high-risk of developing metastases.