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.

Final efficacy and safety results and biomarker analysis of a phase 2 study of cabozantinib in Japanese patients with advanced renal cell carcinoma.

BACKGROUND: Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment. METHODS: Japanese patients with RCC who received at least one prior VEGFR-TKI were enrolled and received cabozantinib 60 mg orally once daily. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory analyses included the relationship between plasma protein hepatocyte growth factor (HGF) levels and treatment responses. RESULTS: In total, 35 patients were enrolled. The median treatment duration was 58.3 (range 5.1-131.4) weeks. The objective response rate was 25.7% (90% confidence interval [CI] 14.1-40.6). Kaplan-Meier estimate of median progression-free survival was 11.1 months (95% CI 7.4-18.4). The estimated progression-free survival proportion was 73.1% (95% CI 54.6-85.0) at 6 months. Median overall survival was not reached. Adverse events were consistent with those in METEOR and the safety profile was acceptable. Nonresponders to cabozantinib showed relatively higher HGF levels than responders at baseline. CONCLUSIONS: Updated analyses demonstrate the long-term efficacy and safety of cabozantinib in Japanese patients with advanced RCC after at least one VEGFR-TKI therapy. Responders tended to show lower baseline HGF levels ClinicalTrials.gov Identifier: NCT03339219.

A high serum dehydroepiandrosterone concentration is a predictor of candidates for active surveillance in men with serum prostate-specific antigen < 10 ng/mL.

BACKGROUND: There is no consensus on the role of serum dehydroepiandrosterone (DHEA) concentrations in the detection of prostate cancer. This study examined the effectiveness of serum DHEA in predicting candidate patients for active surveillance (AS) prior to prostate biopsy. METHODS: A systematic prostate needle biopsy was performed in 203 men with serum PSA levels of < 10 ng/mL to detect prostate cancer. Serum DHEA concentrations were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) just before biopsy. Patient's age, serum prostate-specific antigen (PSA) levels, prostate volume, and serum DHEA concentrations were compared with pathological findings in multivariate analyses. RESULTS: The median patient's age, PSA, serum DHEA concentration and prostate volume were 68 years, 5.5 ng/mL, 1654.7 pg/mL, and 31.2 mL, respectively. In a multivariate analysis, low PSA values, high serum DHEA concentrations, and large prostate volume were significant predictors of the patients with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 who are candidate for AS. The DHEA cut-off point for predicting BPH or prostate cancer with a Gleason score of ≤ 3 + 4 was 2188 pg/mL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 33.7%, 96.0%, 98.4%, and 16.9%, respectively. CONCLUSION: The study indicated that higher serum DHEA concentrations prior to prostate biopsy might predict the patients with BPH or prostate cancer with a Gleason score ≤ 3 + 4 who are candidate for AS, in men with PSA of < 10 ng/mL.

Administration of radium-223 and the prognosis in Japanese bone metastatic castration-resistant prostate cancer patients: A large database study.

BACKGROUND: The ALSYMPCA trial revealed radium-223 (Ra-223) to be a life-prolonging agent for bone metastatic castration-resistant prostate cancer (CRPC). However, only 2.8% of enrolled patients in that clinical trial were Asian, and no Japanese patients were enrolled. Several retrospective studies have been published concerning Japanese bone metastatic CRPC patients receiving Ra-223. However, no study has yet reported the correlation between Ra-223 induction and the survival in Japanese bone metastatic CRPC patients. This study investigated the effect of Ra-223 as a life-prolonging agent in a large Japanese healthcare fee database. METHODS: A total of around 410 000 prostate cancer patients were extracted from this database, and 25 934 were diagnosed with CRPC. In these patients, the age, date of the CRPC diagnosis, date of Ra-223 induction, and prognosis were analyzed. RESULTS: A total of 1628 patients received Ra-223, and 6693 patients were diagnosed with bone metastasis CRPC, with the remaining 17 613 patients diagnosed with CRPC without bone metastasis. The patients who completed six courses of Ra-223 showed a significantly more favorable overall and cancer-specific survival than those who received ≤5 courses (p < 0.0001 and p < 0.0001, respectively). For time from CRPC diagnosis date to death, the Ra-223 induction group showed a significantly more favorable prognosis with regard to both the overall and cancer-specific survival than the bone metastatic CRPC patients without Ra-223 (p < 0.0001 and p < 0.0001, respectively). CONCLUSIONS: Bone metastatic CRPC patients who received Ra-223 showed a significantly better prognosis than bone metastatic CPRC patients who did not receive Ra-223.

A novel prediction model for the completion of six cycles of radium-223 treatment and survival in patients with metastatic castration-resistant prostate cancer.

PURPOSE: We evaluated the predictive factors for completion of all six cycles of radium-223 (Ra-223) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). We also developed a novel prediction model for Ra-223 treatment completion using these predictors. METHODS: We retrospectively reviewed data from 122 patients with mCRPC who were treated with Ra-223. The predictive factors for the completion of six cycles of Ra-223 treatment were evaluated. Statistically significant predictive factors were then used to develop a prediction model for treatment completion. Finally, using this prediction model, we classified the overall survival (OS) of the entire cohort into three groups. RESULTS: We identified three significant variables as the predictive factors for treatment completion: baseline alkaline phosphatase (ALP) level, baseline hemoglobin (Hb) level, and baseline pain. The three groups generated using the prediction model were: group 1 (patients with three predictive factors, i.e., ALP < median, Hb ≥ median, and no pain), group 2 (patients with one to two predictive factors), and group 3 (patients without any predictive factors). The treatment completion rates differed between the three groups significantly. Furthermore, the OS also differed among the groups significantly. CONCLUSION: Our study suggested that the baseline ALP level, baseline Hb level, and baseline pain were the predictive factors of completion of all six cycles of Ra-223 treatment in patients with mCRPC. Our prediction model consisting of these factors could predict not only the completion of Ra-223 treatment, but also the post-treatment survival. This model can thus be useful for selection of patients for Ra-223 treatment.

Prognosis and safety of radium-223 with concurrent abiraterone acetate or enzalutamide use for metastatic castration-resistant prostate cancer: Real-world data of Japanese patients.

Objectives: To evaluate the real-world data on the efficacy and safety of a combination therapy with radium-223 (Ra-223) and second-generation androgen-receptor targeting agents (ARTAs), including abiraterone acetate (ABI) and enzalutamide (ENZ), among Japanese patients with bone metastatic castration-resistant prostate cancer (CRPC). Patients and methods: We retrospectively reviewed 79 patients with bone metastatic CRPC who were treated with Ra-223. The number of patients with concurrent ARTA use was 24:17 receiving ABI and 7 receiving ENZ. We evaluated the overall survival (OS) according to ARTA use and compared the survival of patients treated with Ra-223 with or without ARTA using multivariate analysis. Results: The median survival in the entire cohort was 23.5 months. The patients receiving Ra-223 combined with ARTA showed a tendency of better OS than patients treated with Ra-223 alone, although no significant difference was observed (median OS, 26.5 vs 23.5 months; P = .115). A multivariate analysis showed that the extent of disease on bone scan (EOD) scores and pain at baseline were significant predictors of OS. The concurrent use of bone-modifying agents (BMAs) was not significant for favorable OS (P = .050). However, the concurrent use of second-generation ARTA was not a significant factor for OS. Regarding safety, a bone fracture occurred in only one (4.2%) of 24 patients treated with combined Ra-223 and ARTA therapy. Conclusion: Our real-world data analysis suggested that Ra-223 combined with a second-generation ARTA is well tolerated in Japanese patients. The EOD score and pain at baseline are significant prognostic factors for OS, but the concurrent use of second-generation ARTA has no influence on OS among men treated with Ra-223. The concurrent use of BMA yields a marginally favorable OS.

A lower psoas muscle index predicts a poorer prognosis in metastatic hormone-naïve prostate cancer.

Introduction: A recent investigation revealed that sarcopenia was associated with a poorer prognosis in some solid malignancies, including prostate cancer. In most reports, sarcopenia was defined as a low psoas volume on CT. This study investigated the association of sarcopenia, determined according to the psoas muscle volume and density on CT, with the prognosis in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: A total of 66 patients initially diagnosed with mHNPC were enrolled in this study. Skeletal muscle was evaluated according to the psoas muscle index density (PMID) on computed tomography scans. The psoas muscle volume was calculated at the level of L3 and CT density was evaluated as the mean CT density at the psoas muscle area. We divided the patients into higher and lower PMID groups. Results: The lower PMID group (on both sides) showed a poorer overall survival than the higher PMID group (Right: 32.5 vs 99.0 months in Rt PMID, P = .014; Left: 36.0 vs 100.0 months in Lt PMID, P = .029). The lower PMID group (on both sides) showed a shorter time to CRPC (Right: 9.0 vs 42.0 months in Rt PMID, P = .006; Left: 9.0 vs 31.0 months in Lt PMID, P = .005). A multivariate analysis showed that lower Rt PMID and Lt PMID were independent risk factors for poorer OS (HR:2.02, 95%CI: 1.04-3.90, P = .037, HR:2.29, 95%CI: 1.18-4.47, P = .015, respectively). For CRPC, both Rt and Lt lower PMID also showed independent risk factors for shorter time to CRPC (HR:2.39, 95%CI: 1.23-4.62, P = .010, HR:2.43, 95%CI: 1.23-4.78, P = .010, respectively). Conclusions: Among mHNPC patients, both lower PMID groups showed a poorer overall survival and shorter time to CRPC than the higher PMID groups.

Prognostic value of automated bone scan index for predicting overall survival among bone metastatic castration resistant prostate cancer patients treated with radium-223.

Introduction: The objective of this study was to evaluate automated bone scan index (aBSI) as a prognostic biomarker for overall survival (OS) in bone-metastatic, castration-resistant prostate cancer (mCRPC) patients treated with radium-223 (Ra-223). Materials and methods: We identified 42 men treated with Ra-223 for mCRPC. We investigated aBSI as an independent prognostic factor by multivariate analysis. Moreover, we evaluated the prognostic value of the aBSI after 12 weeks after the first cycle of Ra-223 administration and aBSI change from baseline to after 12 weeks (ΔBSI). Results: Median baseline PSA and aBSI were 42.8 ng/mL and 1.5%, respectively. Median OS was 20.7 months. Multivariate analysis showed that baseline aBSI was a significant prognostic factor for OS. The aBSI at 12 weeks after first Ra-223 administration also exhibited significant prognostic value for OS, while we found no evidence of prognostic value for ΔBSI. Conclusions: Baseline aBSI may be a significant prognostic factor for OS in bone-metastatic CRPC patients treated with Ra-223.

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.

A retrospective study on the possible systematic inflammatory response markers to predict the prognosis of patients with bladder cancer undergoing radial cystectomy.

Recent studies have shown that several inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), lymphocyte-to-platelet ratio (LPR), De Retis and prognostic nutritional index (PNI), can function as useful prognostic factors in a number of malignancies. The present study aimed to assess the most reliable inflammatory tumor marker in patients with bladder cancer who have undergone radical cystectomy. A total of 161 cases underwent radical cystectomy between 1994 and 2014 at Yokohama City University Medical Center (Yokohama, Japan). Of these patients, the 107 who had data for the NLR, MLR, LPR, De Retis and PNI were enrolled in the present study. The correlation between recurrence-free survival (RFS) or overall survival (OS) and inflammatory tumor markers were examined. Regarding the RFS, the only noteworthy finding was that a lower PNI was associated with a significantly poorer RFS compared with higher PNI (P=0.028). Regarding the OS, lower LPR and PNI were associated with a significantly poorer OS compared with higher values (P=0.048 and P=0.036, respectively). The present study revealed that a low PNI more accurately predicts a worse RFS and OS compared with other systemic inflammatory risk factors.

Dynamic changes of bone metastasis predict bone-predominant status to benefit from radium-223 dichloride for patients with castration-resistant prostate cancer.

BACKGROUND: To best employ radium-223 dichloride (Ra-223) for patients with castration-resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone-predominant status in patients treated with Ra-223. METHODS: We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra-223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra-223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression-free survival (PFS). RESULTS: During the median follow-up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13-1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04-2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02-2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11-2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra-223 treatment. This was associated with non-bone metastasis progression, especially visceral metastasis, and overall survival. CONCLUSIONS: Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone-predominant metastasis type to benefit from Ra-223.

Clinical outcome of surgical management for symptomatic metastatic spinal cord compression from prostate cancer.

BACKGROUND: Metastatic spinal cord compression (MSCC) from prostate cancer (PC) influences not only patients' prognosis but also their quality of life. However, little is known about the clinical outcome of surgery for MSCC from PC. We evaluated both the oncological and functional outcomes of decompression and reconstruction surgery for patients with symptomatic MSCC from PC. METHODS: We assessed 19 patients who underwent decompression and reconstruction surgery for symptomatic MSCC from PC. Of these 19 patients, 8 had metastatic hormone-naïve PC (mHNPC) and 11 had metastatic castration-resistant PC (mCRPC). RESULTS: The median age of the patients with mHNPC and mCRPC was 72 and 65 years, respectively. The median prostate-specific antigen level at the time of diagnosis of MSCC in patients with mHNPC and mCRPC was 910 and 67 ng/mL, respectively. Although two of eight patients (25.0%) with mHNPC were ambulatory preoperatively, six patients (75.0%) were ambulatory postoperatively. Among 11 patients with mCRPC, only 3 (27.3%) were ambulatory preoperatively, while 6 (54.5%) were ambulatory postoperatively. The median postoperative overall survival among patients with mHNPC and mCRPC were not reached and 8 months, respectively. CONCLUSIONS: Decompression and reconstruction surgery for symptomatic MSCC from PC might contribute to a favorable functional outcome among men with mHNPC and mCRPC. However, its role in improving the oncological outcome remains unclear. The treatment strategy should be chosen by shared decision-making among patients, urologists, radiation oncologists, and orthopedic surgeons.

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.

Cabozantinib in advanced renal cell carcinoma: A phase II, open-label, single-arm study of Japanese patients.

OBJECTIVES: To evaluate the efficacy and safety of cabozantinib, through a bridging study to METEOR, in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy. METHODS: This phase II, open-label, single-arm study (ClinicalTrials.gov registration number: NCT03339219) included adult Japanese patients with advanced renal cell carcinoma and measurable disease who had received one or more tyrosine kinase inhibitors. Patients received cabozantinib 60 mg orally once daily while there was clinical benefit, or until unacceptable toxicity or disease progression. The primary end-point was objective response rate per Response Evaluation Criteria in Solid Tumors Version 1.1. Secondary end-points included clinical benefit rate (complete or partial response, or ≥8-week stable disease), progression-free survival, overall survival and safety. RESULTS: Of the 35 patients enrolled, 68.6%, 22.9% and 8.6% had previously received one, two and three prior tyrosine kinase inhibitors, respectively. The median duration of cabozantinib exposure was 27.0 weeks (range 5.1-43.0 weeks). The objective response rate was 20.0% (90% confidence interval 9.8-34.3%), and the clinical benefit rate was 85.7% (95% confidence interval 69.7-95.2%). The 6-month estimated progression-free survival was 72.3% (95% confidence interval 53.3-84.6%); the median progression-free survival and overall survival were not reached. All patients reported adverse events, which were manageable by supportive treatment or dose modification; two patients (5.7%) discontinued therapy due to adverse events. CONCLUSIONS: The results showed that findings from METEOR can be extrapolated, and that cabozantinib 60 mg/day is a viable treatment option in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy.

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.

Does screening for prostate cancer improve cancer-specific mortality in Asian men? Real-world data in Yokosuka City 15 years after introducing PSA-based population screening.

BACKGROUND: Studies of prostate-specific antigen (PSA)-based population screening have been conducted in western countries, but there is little data in Asian populations. The objective of this study was to determine the efficacy of PSA screening in Asian men using real-world data over a period of 15 years after introducing population screening in Yokosuka City, Japan. METHODS: We investigated patients with pathologically diagnosed prostate cancer at four hospitals and two clinics across the Yokosuka area (Miura peninsula) between April 2001 and March 2015. Patients were divided into two groups; the S group consisted of those diagnosed by PSA-based population screening in Yokosuka City and the NS group consisted of those diagnosed by methods other than screening. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated using the Kaplan-Meier method with the log-rank test to compare survival between the two groups. Clinical and pathological factors for cancer-specific mortality were assessed with Cox regression analyses to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 3094 patients had been diagnosed with prostate cancer over the 15-year period. The median follow-up period was 77 months. The S group and the NS group consisted of 977 and 2117 patients, respectively. Patients in the S group were younger (age: 71 years vs 73 years, P < .001) and had a lower Charlson comorbidity index (CCI) with favorable oncological factors, such as lower initial PSA, Gleason score (GS), and risk category. Kaplan-Meier curves for OS and CSS revealed significant differences between the two groups (OS: P < .001, CSS: P < .001). Analysis with Cox proportional hazards model indicated the NS group (HR: 1.584, 95% CI, 1.065-2.356, P = .023), a CCI > 4 (HR: 1.552, 95% CI, 1.136-2.120, P = .006), a GS ≥ 8 (HR: 4.869, 95% CI, 2.631-9.001, P < .001), and nonlocalized cancer (locally advanced; HR: 2.632, 95% CI, 1.676-4.133, P < .001, advanced; HR: 9.468, 95% CI, 6.279-14.278, P < .001) as independent risk factors for cancer-specific mortality. CONCLUSIONS: PSA-based population screening of prostate cancer might be useful in the Japanese population.