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PurposeClinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated.MethodsThe medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan–Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors.ResultsMedian follow-up was 2.95 years, median CRPC-free survival was 21.9 months and median OS was 5.37 years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220 IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5 months, 17.9 months in intermediate-risk patients with two or three factors, and 11.0 months in high-risk patients with four factors. Median OS was 4.72 years in intermediate- and 2.44 years in high-risk patients. It was not reached in low-risk patients.ConclusionIn this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients.

PurposeThis study investigated the impact of treatment intensification with upfront docetaxel (DOC) or abiraterone (ABI) plus prednisolone on survival outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) by comparing it with androgen deprivation therapy (ADT) monotherapy or combined androgen blockade (CAB) using propensity score matching (PSM).MethodsOutcomes from 278 CHAARTED high-volume patients receiving upfront DOC (92 patients) or upfront ABI (186 patients) were compared to those from 354 patients receiving ADT or CAB. PSM was conducted to assess castration-resistant prostate cancer-free survival (CRPCFS) and overall survival (OS).ResultsAfter PSM, patient distributions between the three groups were well balanced. After 1:1 PSM, patients receiving upfront ABI had significantly better CRPCFS than those receiving ADT/CAB or upfront DOC [hazard ratio (HR) 0.39; 95% CI 0.27–0.56 vs. HR 0.50; 95% CI 0.30–0.82, respectively]. No significant difference in CRPCFS was observed between the upfront DOC and ADT/CAB groups (HR 0.75; 95% CI 0.50–1.12). Patients receiving upfront DOC and upfront ABI had significantly better OS than those receiving ADT/CAB (HR 0.54; 95% CI 0.0.30–0.98 vs. HR 0.49; 95% CI 0.29–0.84, respectively). However, no significant difference in OS was observed between upfront ABI and upfront DOC (hazard ratio 0.84; 95% CI 0.34–2.06).ConclusionThe comparison of real-world retrospective cohorts showed that treatment intensification with upfront DOC or upfront ABI promoted better OS compared to ADT alone or CAB in patients with high-volume mCSPC after PSM. However, no difference in OS was observed between upfront DOC and upfront ABI.

Background Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. Methods We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n  = 20) and the non-anemia-ABI group ( n  = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019). Results We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P  = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group ( n  = 68) ( P  < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups ( n  = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P  < 0.001), whereas ABI did not prolong the PFS of patients with anemia. Conclusion Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited.

PurposeWe assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies.MethodsThe medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted.ResultsA total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34–0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33–1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42–2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups.ConclusionsUpfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

We conducted a risk-adapted upfront docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here, we reported an interim analysis of the study. The study enrolled 68 patients with newly diagnosed mHSPC between 2016 and 2018. According to the presence of visceral metastasis, an EOD score ≥ 3, or prostate-specific antigen (PSA) level at 3 months of ≥ 1 ng/mL, patients were divided into low- and high-risk groups. Patients were treated with androgen deprivation therapy (ADT) with or without bicalutamide; those in the high-risk group received upfront treatment involving six cycles of DOC (70 mg/m2). Short-term treatment effect, adverse events, and quality of life (QOL) were evaluated. Fifty (73.5%) were classified in the high-risk group, and 46 (67%) received upfront ADT + DOC. In the ADT + DOC group, 43.5% (20/46) patients achieved a PSA level ≤ 0.2 ng/mL. PSA nadir and time to PSA nadir were 0.291 ng/mL and 288 days, respectively. In the ADT + DOC group, 76.1% (35/42) patients had adverse events (AEs) of grade ≥ 3. During a median follow-up of 18.5 months, 36.4% (8/22) patients in the ADT group and 43.5% (20/46) in the ADT + DOC group had CRPC. Two QOL scores including the physical status and appetite loss at 6 months significantly worsened in the ADT + DOC group but was resolved by 12 months. Upfront DOC achieved high PSA responses without long-term QOL deterioration. However, the short-term outcomes were limited. Longer follow-up is needed to determine the survival advantage.

Background The purpose of this study was to identify predictive factors associated with conditional net survival in patients with metastatic hormone‐naive prostate cancer (mHNPC) initially treated with androgen deprivation therapy (ADT). Methods At nine hospitals in Tohoku, Japan, the medical records of 605 consecutive patients with mHNPC who initially received ADT were retrospectively reviewed. The Pohar Perme estimator was used to calculate conditional net cancer‐specific survival (CSS) and overall survival (OS) for up to 5 years subsequent to the diagnosis. Using multiple imputation, proportional hazard ratios for conditional CSS and OS were calculated with adjusted Cox regression models. Results During a median follow up of 2.95 years, 208 patients died, of which 169 died due to progressive prostate cancer. At baseline, the 5‐year CSS and OS rates were 65.5% and 58.2%, respectively. Conditional 5‐year net CSS and OS survival gradually increased for all the patients. In patients given a 5‐year survivorship, the conditional 5‐year net CSS and OS rates improved to 0.906 and 0.811, respectively. Only the extent of disease score (EOD) ≥2 remained a prognostic factor for CSS and OS up to 5 years; as survival time increased, other variables were no longer independent prognostic factors. Conclusions The conditional 5‐year net CSS and OS in patients with mHNPC gradually increased; thus, the risk of mortality decreased with increasing survival. The patient's risk profile changed over time. EOD remained an independent prognostic factor for CSS and OS after 5‐year follow‐up. Conditional net survival can play a role in clinical decision‐making, providing intriguing information for cancer survivors. The conditional 5‐year net CSS and OS in patients with mHNPC gradually increased. EOD remained an independent prognostic factor for CSS and OS after 5‐year follow‐up. Conditional net survival can play a role in clinical decision‐making, providing intriguing information for cancer survivors.

PurposeTo investigate the association between the Geriatric Nutritional Risk Index (GNRI) and prognosis of patients with metastatic hormone-naïve prostate cancer (mHNPC) and to design the optimal risk score predicting for prognosis.MethodsWe retrospectively reviewed data from the Michinoku Japan Urological Cancer Study Group database, containing information about 656 patients with mHNPC who initially received androgen-deprivation therapy between 2005 and 2017. The baseline GNRI was calculated using serum albumin level and body mass index. Poor nutrition was defined as GNRI < 92.0. The impact of GNRI, CHAARTED criteria, and laboratory parameters on oncological outcomes was investigated using the multivariable Cox regression models. We developed the risk comprising GNRI and laboratory parameters and compared its prognostic performance with the CHAARTED criteria using the receiver operating characteristic curve with the DeLong method.ResultsOf 339 patients with sufficient data, 66 (19%) were diagnosed with poor nutrition. Multivariate analyses showed that GNRI < 92.0 was an independent prognostic factor of cancer-specific survival [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.04–2.98, P = 0.035] and overall survival (HR 1.80; 95% CI 1.13–2.89, P = 0.013), in addition to hemoglobin (Hb) and lactic dehydrogenase (LDH) levels. We designed the risk score comprising GNRI < 92.0, Hb < 13.0 g/dL, and LDH > 222 IU/L. The predictive value of the risk score was significantly superior to that of the CHAARTED criteria.ConclusionsPoor nutrition may predict mortality in patients with mHNPC. Risk factors, such as nutritional status and laboratory parameters, may be useful in decision-making regarding aggressive treatments for patients with mHNPC.

PurposeWe determine whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) patients.MethodsWe reviewed the Michinoku Japan Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW)-adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis.ResultsMedian age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir > 0.64 ng/mL and TTN < 7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC. The IPTW-adjusted multivariate model revealed that the unfavorable group had a negative impact on OS in mCRPC patients [hazards ratio (HR) 2.98, P < 0.001].ConclusionsHigher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.

We evaluated the impact of early changes in serum biomarker levels on the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC) who were initially treated with androgen deprivation therapy (ADT). We retrospectively investigated 330 patients with mHSPC whose serum maker levels were at baseline and at 2–4 months. An optimal Cox regression model was established with the highest optimism-corrected concordance index based on 10-fold cross-validation. The median cancer-specific survival (CSS) and overall survival (OS) were 7.08 and 6.47 years (median follow-up, 2.53 years), respectively. In the final optimal Cox model with serum biomarker levels treated as time-varying covariates, prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP) significantly increased the risk of poor survival in the context of both CSS and OS. Kaplan–Meier curves stratified by the three risk factors of high PSA, low Hb and high ALP desmondtated that median OS were not reached with none of these factors, 6.47 years with one or two factors, and 1.76 years with all three factors.Early changes in serum biomarker levels after ADT may be good prognostic markers for the survival of patients with mHSPC.

Gamma-ray bursts (GRBs) are the most luminous transients in the universe and are utilized as probes of early stars, gravitational wave counterparts and collisionless shock physics. In spite of studies on polarimetry of GRBs in individual wavelengths that characterized intriguing properties of prompt emission and afterglow, no coordinated multi-wavelength measurements have yet been performed. Here we report the first coordinated simultaneous polarimetry in the optical and radio bands for the afterglow associated with the typical long GRB 191221B. Our observations successfully caught the radio emission, which is not affected by synchrotron self-absorption, and show that the emission is depolarized in the radio band compared with the optical one. Our simultaneous polarization angle measurement and temporal polarization monitoring indicate the existence of cool electrons that increase the estimate of jet kinetic energy by a factor of more than 4 for this GRB afterglow. Further coordinated multi-wavelength polarimetric campaigns would improve our understanding of the total jet energies and magnetic field configurations in the emission regions of various types of GRBs, which are required to comprehend the mass scales of their progenitor systems and the physics of collisionless shocks.Simultaneous polarimetry measurements in the optical and radio bands for the afterglow emission of GRB 191221B provide insights into particle acceleration and total energy budget of gamma-ray bursts.