Treatment trends in patients with de novo metastatic prostate cancer in the era of upfront combination therapy.

OBJECTIVES: The objective of this study is to assess the trends in treatment selection for patients with de novo metastatic castration-sensitive prostate cancer in the era of upfront combination therapy. METHODS: This multicenter retrospective study included 595 patients treated with either upfront combination therapy (upfront novel hormonal therapies and taxane-based chemotherapy) or vintage therapy (androgen deprivation therapy with or without bicalutamide) between 2016 and 2021. High tumor burden metastatic disease was defined when a patient met the CHAARTED or LATITUDE criteria. We evaluated trends in treatment selection and reasons for selecting vintage therapy. RESULTS: Of the 595, 123 and 472 patients were classified as having low and high tumor-burden disease, respectively. The Use of upfront combination therapy was found to be rapidly increasing with utilization rates of 72% and 54% in 2021 for high and low tumor-burden disease, respectively. Multivariable logistic regression analysis found older age, poor performance status, and nonacademic center were significantly associated with the selection of vintage therapy. Of the 163 patients who received vintage hormone therapy after approval of upfront therapy, 74.2% had a specific reason for avoiding upfront therapy. The reasons for selecting vintage therapy included refusal (39.8%), older age (67.6%), frailty (56.3%), and comorbidity (40.8%). Furthermore, 16.9% of patients declined upfront combination therapy due to cost concerns. CONCLUSION: Upfront combination therapy use has 72% and 54% prevalence among patients with high and low tumor burden diseases, respectively, in this current practice. Older age, poor performance status, and facility bias were negatively associated with the use of upfront combination therapy.

Prediction of Postoperative Range of Motion after Mobile-Bearing Medial Unicompartmental Knee Arthroplasty from the Preoperative Range of Motion and Other Preoperative Factors.

Postoperative flexion after unicompartmental knee arthroplasty might be predicted from the preoperative range of motion and other preoperative factors, but this has not been sufficiently investigated. Between 2013 and 2017, 198 patients (198 knees) underwent unilateral knee arthroplasty with medial mobile-bearing unicompartmental knee arthroplasty. Range of motion was measured preoperatively and at the time of final follow-up. To investigate the accuracy of the prediction of preoperative to postoperative gain or loss of the flexion angle, we performed receiver operating characteristic analysis. Logistic regression analysis was used to evaluate other predictive factors. Change in flexion angle was significantly strongly and negatively correlated with the preoperative flexion angle (R = - 0.688; 95% confidence interval: -0.755 to -0.607; p < 0.001). Preoperative flexion angle was suggested to be a significant predictor of gain or loss of the flexion angle with the area under the curve of 0.781; the cutoff value calculated using the Youden index was 140 degrees. Logistic regression analysis showed that in addition to the preoperative flexion angle of the operated side, the postoperative flexion range was significantly affected by the patient's height and by the preoperative flexion angle of the contralateral knee. If the preoperative flexion angle in Oxford mobile-bearing medial unicompartmental knee arthroplasty is <140 degrees, the postoperative flexion angle may be improved; if it exceeds 140 degrees, the postoperative flexion angle may worsen. This predictive ability is further improved by consideration of the patient's height and the range of motion on the contralateral side.

Real-world effects of novel androgen receptor axis-targeted agents on oncological outcomes in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.

Background: The benefits of novel androgen receptor axis-targeted agents (ARATs) on oncological outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in real-world settings are unclear. Methods: This multi-institutional retrospective study included 178 patients with nmCRPC treated between September 2003 and August 2022. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 76 years and 37 months, respectively. Of the 178 patients, 122 (69%) were treated with novel ARATs after nmCRPC diagnosis. The MFS and OS in the novel ARATs group were significantly longer than those in the control group (P < 0.001 and P = 0.020, respectively). In multivariable analyses, a prostate-specific antigen doubling time (PSADT) of <3 months and novel ARATs were independently and significantly associated with MFS and OS. The effects of novel ARATs on MFS were consistently observed across subgroups stratified by age (<75 years or ≥75 years), history of radical treatment (no or yes), biopsy Gleason score (<9 or ≥9), clinical stage (≤cT3 and cN0, or cT4 or cN1), and PSADT (≥3 months or <3 months). Conclusion: Novel ARATs were significantly associated with improved oncological outcomes in patients with nmCRPC in a real-world setting, regardless of tumor aggressiveness.

Inhibitory action of B-type natriuretic peptide on adrenocorticotropic hormone in patients with acute coronary syndrome.

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (ß = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.

Trends in the use of local intervention for metastatic hormone-naïve prostate cancer: A multicenter retrospective study.

OBJECTIVE: To evaluated the trends of local intervention and their impact on oncological outcomes in metastatic hormone-naïve prostate cancer (mHNPC) in real-world practice. METHODS: This retrospective multicenter study included 760 patients treated with either androgen deprivation therapy (ADT) without local treatment (no castration-resistant prostate cancer [CRPC] progression within 12 months, control group) or ADT plus local intervention (intervention group) between January 2005 and March 2022. We evaluated the trends in the use of local intervention in patients with mHNPC and factors associated with CRPC-free survival in the intervention group. RESULTS: The use of local intervention gradually increased in combination with upfront combination treatment (docetaxel or androgen receptor axis-targeted agents) for the duration of our study. The number of patients with local intervention combined with upfront treatment was significantly higher in patients with high tumor burden disease than in those with low tumor burden disease. Of the 108 patients who received local intervention, a duration of ≤7 months of initial therapy before local intervention and a level of prostate-specific antigen ≥0.20 ng/mL at the time of local intervention were significantly associated with poor CRPC-free survival. CONCLUSIONS: The use of local intervention in combination with upfront therapy to treat mHNPC increased for the duration of our study regardless of the tumor burden. Local intervention in addition to the standard of care for mHNPC may be a feasible treatment option for selected patients, taking into consideration the duration of and response to initial treatment.

Impact of nephroureterectomy on postoperative renal function in upper tract urothelial carcinoma: A multicenter retrospective study.

OBJECTIVE: To assess the impact of radical nephroureterectomy on postoperative renal function in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively evaluated 645 patients with UTUC treated with radical nephroureterectomy between January 2000 and May 2022. The primary outcome was the rate of postoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 . Secondary outcomes included the rate of eGFR decline, identification of factors related to eGFR decline, and the impact of comorbidities (diabetes or cardiovascular disease) on postoperative eGFR at 1 year. RESULTS: The median preoperative and postoperative eGFR levels were 55.6 and 43.3 mL/min/1.73 m2 , respectively. The rate of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 was 40.9% and 9.0%, respectively. The median decline in eGFR after surgery was 25.1%. The presence of preoperative unilateral hydronephrosis and eGFR <60 mL/min/1.73 m2 was significantly associated with a low decline of postoperative eGFR and poor survival. The impact of the presence of comorbidities on postoperative eGFR at 1 year was significant (p < 0.001). CONCLUSION: Impaired renal function is prevalent in patients with UTUC. The rate of patients with postoperative eGFR ≥60 mL/min/1.73 m2 was 9.0%. The presence of preoperative renal impairment was significantly related to a low decline in postoperative eGFR and poor survival. The presence of comorbidities had a significant effect on eGFR decline 1 year after radical nephroureterectomy.

Is simultaneous bilateral unicompartmental knee arthroplasty and total knee arthroplasty better than simultaneous bilateral total knee arthroplasty?

INTRODUCTION: This retrospective study aims to clarify if there are benefits of performing unicompartmental knee arthroplasty (UKA) on just one indicated side in patients who undergo simultaneous bilateral knee arthroplasty. MATERIALS AND METHODS: We compared 33 cases of simultaneous bilateral UKA/total knee arthroplasty (TKA) (S-UT) with 99 cases of simultaneous bilateral TKA (S-TT). Comparison included blood tests [C-reactive protein (CRP), albumin, and D-dimer], the incidence of deep vein thrombosis (DVT), range of motion (ROM), and clinical scores before and 1 year after surgery. RESULTS: Clinical scores were not significantly different between the groups. The postoperative flexion angle was significantly better in UKA sides. Blood tests showed that the S-UT had a significantly higher albumin value at 4 and 7 days after surgery. The CRP value at 4 and 7 days, and the D-dimer value at 7 and 14 days after surgery were significantly lower in the S-UT. The S-UT had significantly lower incidence of DVT. CONCLUSIONS: In cases of bilateral arthroplasty, if there is an indication on only one side, a better flexion angle can be obtained by UKA on that side, and with less surgical invasion. Moreover, the incidence of DVT is low, which is considered to be a benefit of performing UKA on just one side.

Trends of incidence and age in adults with testicular germ cell tumors: a two-decade multicenter retrospective study.

Background: Testicular germ cell tumors (GCTs) are the most common type of cancer in adolescent boys and young adult men, but the age at onset has been increasing. However, little is known regarding the incidence and age of patients with testicular GCTs in Japan because the incidence there is low. Methods: We retrospectively reviewed the medical records of patients with GCTs in seven hospitals between 2001 and 2021. We compared the incidences of testicular GCTs, ages at onset, pathological types (seminoma or nonseminoma), and clinical stages in patients with GCTs between the periods 2001-2010 and 2011-2021. Results: We identified 193 adults (≥20 years of age) with testicular GCTs; their median age was 37 years [interquartile range (IQR), 29-47 years]. Of these patients, 87 (45.1%) were ≥40 years of age at diagnosis. The proportion of patients aged ≥40 years was significantly higher in the period 2011-2021 (54.8%) than in 2001-2010 (30.8%; P=0.001). The incidence of seminoma was significantly higher in the period 2011-2021, but clinical stage did not differ significantly between the two periods. The population-adjusted incidence among patients in their 40s was 3.4-fold higher in 2011-2021 than in 2001-2010. Conclusions: The number of patients with GCTs aged ≥40 years was significantly higher in 2011-2021, even in a population-adjusted analysis. Treatment strategies need to be adapted to older testicular germ cell tumor patients.

Oncological and functional outcomes of female reproductive organ-sparing radical cystectomy and ileal neobladder construction.

OBJECTIVES: To examine the oncological and urinary functional outcomes of reproductive organ-sparing radical cystectomy (ROS-RC) and U-shaped ileal neobladder construction in females compared with male patients. METHODS: We retrospectively examined 357 patients (281 male and 76 female) with muscle-invasive bladder cancer who were treated with RC plus U-shaped ileal neobladder construction between May 1996 and July 2021. All female patients were treated with ROS-RC. We compared disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and urinary functional outcomes between male and female patients. We evaluated the effect of gender on DFS, CSS, and OS. Furthermore, urinary functional outcomes were evaluated in 140 males and 48 females using a pressure-flow study at 3, 6, 9, and 12 months postoperatively. RESULTS: Female patients were considerably older than male patients at the time of radical cystectomy. No significant difference was noted in the tumor stage preoperatively. The multivariable Cox regression analysis with an inverse probability treatment weighted model revealed that the female gender was not significantly related to DFS, CSS, and OS. Moreover, urinary functions at 12 months were not markedly different between males and females, except for the capacity of the neobladder, detrusor pressure, and maximum urethral closure pressure. CONCLUSIONS: This study demonstrates that female patients with ROS-RC and U-shaped ileal neobladder construction did not significantly correlate with worse oncological outcomes. The combination of ROS-RC and U-shaped ileal neobladder construction might attain adequate urinary function without sacrificing oncologic outcomes.

Comparison of efficacy and medical costs between upfront docetaxel and abiraterone treatments of metastatic hormone-sensitive prostate cancer patients in real-world practice: a multicenter retrospective study.

PURPOSE: We compared the real-world efficacy and medical costs for treatment with upfront docetaxel (DOC) and abiraterone acetate (ABI) up to progression-free survival 2 (PFS2) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This multicenter retrospective study included 340 patients with mHSPC treated with either upfront DOC or upfront ABI between October 2015 and December 2021. We compared PFS2 and medical costs between the two treatment groups. PFS2 was defined as the time from first-line therapy to progression on second-line therapy. Medical costs were estimated using the National Health Insurance drug prices in 2022 in Japan. RESULTS: The upfront DOC and ABI groups included 107 and 233 patients, respectively. The incidence of metastatic castration-resistant PC progression was significantly higher in the upfront DOC group compared with the incidence in the upfront ABI group. However, no significant differences in PFS2 were observed between the two treatment groups. Monthly medical costs per patient were significantly higher in the upfront ABI group ($3453) compared with the costs in the upfront DOC group ($1239, P < 0.001). The cost differences were significantly influenced by differences in the length of androgen deprivation therapy monotherapy (DOC group, 13.4 months vs. ABI group, 0.0 months). CONCLUSIONS: We observed a significant cost benefit in the upfront DOC group in Japanese real-world practice, while the PFS2 rates were similar between the groups. Upfront DOC was a more cost-effective option for men with mHSPC who were eligible for toxic chemotherapy.

Long-term outcomes of percutaneous revascularization for internal mammary artery-left anterior descending artery bypass failure.

Despite the excellent long-term results of internal mammary artery (IMA)-left anterior descending (LAD) bypass, percutaneous revascularization of IMA is sometimes required for IMA-LAD bypass failure. However, its clinical outcomes have not been fully elucidated. The aim of this study was to investigate the long-term clinical outcomes, including target lesion revascularization (TLR) following contemporary percutaneous revascularization of failed IMA bypass graft. We examined data of 59 patients who had undergone percutaneous revascularization of IMA due to IMA-LAD bypass failure at nine hospitals. Patients with IMA graft used for Y-composite graft or sequential bypass graft were excluded. The incidence of TLR was primarily examined, whereas other clinical outcomes including cardiac death, myocardial infarction, and target vessel revascularization were also evaluated. Mean age of the enrolled patients was 67.4 ± 11.3 years, and 74.6% were men. Forty patients (67.8%) had anastomotic lesions, and 17 (28.8%) underwent revascularization within three months after bypass surgery. Procedural success was achieved in 55 (93.2%) patients. Stent implantation was performed in 13 patients (22.0%). During a median follow-up of 1401 days (interquartile range, 282-2521 days), TLR was required in six patients (8.5% at 1, 3, and 5 years). Patients who underwent percutaneous revascularization within 3 months after surgery tended to have a higher incidence of TLR. Clinical outcomes of IMA revascularization for IMA-LAD bypass failure were acceptable.

Posterior tibial slope and meniscal slope correlate with in vivo tibial internal rotation during running and drop jump.

PURPOSE: The relationship between tibial bony and meniscus anatomy and knee kinematics during in vivo, high-impact activities remains unclear. This study aimed to determine if the posterior tibial slope (PTS) and meniscal slope (MS) are associated with in vivo anterior-posterior translation and internal tibia rotation during running and double-leg drop jumps in healthy knees. METHODS: Nineteen collegiate athletes performed fast running at 5.0 m/s on an instrumented treadmill and double-leg drop jump from a 60 cm platform while biplane radiographs of the knee were acquired at 150 Hz. Tibiofemoral kinematics were determined using a validated model-based tracking process. Medial and lateral PTS and MS were measured using magnetic resonance imaging (MRI). RESULTS: In fast running, more internal tibia rotation was associated with greater PTS (ρ = 0.336, P = 0.039) and MS (ρ = 0.405, P = 0.012) in the medial knee compartment. In the double-leg drop jump, more internal tibia rotation was associated with greater PTS (ρ = 0.431, P = 0.007) and MS (ρ = 0.323, P = 0.005) in the medial knee compartment, as well as a greater PTS in the lateral knee compartment (ρ = 0.445, P = 0.005). CONCLUSION: These findings suggest that the medial and lateral PTS and medial MS are associated with the amount of knee rotation during high-impact activities. These in vivo findings improve our understanding of ACL injury risk by linking bone and meniscus morphology to dynamic kinematics.

Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: A multicenter retrospective study.

BACKGROUND: We aimed to evaluate the effects of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)-free survival in patients with advanced prostate cancer (PC). METHODS: We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 patients with treatment-naïve metastatic castration-sensitive PC (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin-related AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin-related AEs in patients with small body size, postskin AE apalutamide discontinuation rate, and CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy. RESULTS: Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin-related AE rate was not significantly different between the groups (55% vs. 43%, p = 0.761). In the group receiving reduced apalutamide dose, the incidence of skin-related AEs was significantly lower in patients with small body sizes (body weight <67 kg and body mass index <24 kg/m2 ) than in those with other body sizes. The postskin AE apalutamide discontinuation rate was significantly differed between patients receiving the full (50%) and reduced (16.7%) doses. In the 72 patients with mCSPC, CRPC-free survival was not significantly different between the full and reduced dose groups. CONCLUSION: Apalutamide dose reduction was not significantly associated with the incidence of skin-related AEs. However, dose reduction in patients with small body sizes may alleviate skin-related AEs without sacrificing oncological outcomes.

Utility of the Age Discrepancy between Frailty-Based Biological Age and Expected Life Age in Patients with Urological Cancers.

Background: The estimation of biological age is challenging in patients with cancers. We aimed to investigate frailty-based biological ages using frailty-discriminant scores (FDS) and examined the effect of biological-expected life age discrepancy on the prognosis of patients with urological cancers. Methods: We retrospectively evaluated frailty in 1035 patients having urological cancers. Their frailty-based biological age was then defined by the FDS, which is a comprehensive frailty assessment tool, using 1790 noncancer individuals as controls. An expected life age (=chronological age + life expectancy) was subsequently calculated using the 2019 life expectancy table. The primary outcome was the estimation of the biological-expected life age discrepancy between the frailty-based biological age and expected life age in patients with urological cancers. Secondary outcomes were the evaluation of the effect of the biological-expected life age discrepancy on overall survival. Results: We included 405, 466, and 164 patients diagnosed with prostate cancer, urothelial carcinoma, and renal cell carcinoma, respectively. The median chronological age, life expectancy, and estimated frailty-based biological age were 71, 17, and 83 years, respectively. The biological-expected life age discrepancy in any urological cancers, localized diseases, and metastatic diseases was −4.8, −6.3, and +0.15 years, respectively. The biological-expected life age discrepancy of >5 years was significantly associated with poor overall survival. Conclusions: The biological-expected life age discrepancy between frailty-based biological age and expected life age may be helpful in understanding the role of frailty and patient/doctor conversation.

Intramedullary rod insertion places the femoral component more laterally during Oxford medial unicompartmental knee arthroplasty.

BACKGROUND: This study aims to assess the influence of intramedullary rods on the implantation positions of femoral components using Microplasty instrumentation in Oxford unicompartmental knee arthroplasty. We hypothesized that femoral components can be laterally implanted incorrectly when using intramedullary rods. METHODS: This prospective study included all 45 consecutive patients (53 knees) who underwent Oxford unicompartmental knee arthroplasty surgery for anteromedial osteoarthritis or spontaneous osteonecrosis of the knee at our hospital during the study period. A custom-made toolset comprising a triangular caliper and circular trial bearings was used to evaluate the distance between the bearing and the vertical wall of the tibia implant (wall-bearing space) using the caliper at 90° flexion both with and without intramedullary rods. RESULTS: The wall-bearing space was significantly larger when the intramedullary rod was used than when intramedullary rod was not used (1.8 ± 1.1 mm versus 3.4 ± 1.2 mm, P < 0.001). The mean difference of wall-bearing space with and without intramedullary rod was 1.6 ± 0.7 mm. CONCLUSIONS: Femoral components can be laterally implanted incorrectly by an average of 1.6 mm when using intramedullary rods. The wall-bearing space should be evaluated using trial components, and if the relationship is improper, it should be corrected before keel slot preparation.

Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia-Reperfusion Injury in Diet-Induced Obesity.

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia-reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia-reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

BACKGROUND: The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. METHODS: This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. RESULTS: The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. CONCLUSION: Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

The impact of eligibility for maintenance immunotherapy on prognosis in patients with unresectable or metastatic urothelial carcinoma.

Objectives: To investigate the eligibility for maintenance immunotherapy and its impact on the prognosis of advanced urothelial carcinoma treated with first-line chemotherapy, as the selection biases of the eligible population in the JAVELIN Bladder 100 trial remain unclear. Methods: We retrospectively evaluated 213 patients (median age, 71 years) with unresectable locally advanced or metastatic urothelial carcinoma treated with platinum-based first-line chemotherapy between May 2003 and April 2021. The patients were categorized into the following two groups: progressive disease (PD) within four cycles (trial ineligible group) and non-PD within four cycles (trial eligible group). The primary outcomes were the estimated proportion of trial eligible patients for maintenance immunotherapy. The secondary outcomes were the comparison of the overall survival in the trial eligible and ineligible groups and the impact of radiologic response at the second cycle on the fourth cycle. Results: Among the 213 patients, 81 (38%) were included in the trial eligible group. The trial eligible group had a significantly longer overall survival than the trial ineligible group (P < 0.001). Of 166 patients who had no PD within two cycles, 85 (51%) patients experienced PD within four cycles. Patients with a complete response or partial response at the second cycle had a significantly lower rate of PD at the fourth cycle (42%) than those with stable disease at the second cycle (59%, P = 0.031). Conclusion: We observed 38% of the trial eligible population. Overall survival was significantly different between the trial eligible and ineligible groups.

Prognostic impact of eligibility for adjuvant immunotherapy in locally advanced urothelial cancer.

Objective: To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle-invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Patients and methods: We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3-4 or pN+ without neoadjuvant chemotherapy and ypT2-4 or pN+ treated with neoadjuvant chemotherapy (trial-eligible group) or others (trial-ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease-free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results: The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty-two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI-positive status was significantly associated with poor prognosis among patients in the trial-eligible group. A very high risk (LVI+ or pN+ among the pT3-4 or ypT2-4) was significantly associated with poor prognosis. Conclusion: A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

Prognostic impact of proton pump inhibitors for immunotherapy in advanced urothelial carcinoma.

Objective: To evaluate the effects of the concomitant use of proton pump inhibitors (PPIs) and/or antibiotics (Abs) on oncological outcomes in patients with advanced urothelial carcinoma. Patients and methods: We retrospectively evaluated 155 patients with advanced urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs) between August 2015 and April 2021. The concomitant use of PPI or Abs was defined as any PPI or Abs administered within 30 days before ICI initiation and during ICI therapy. The primary outcomes were the effect of PPI and/or Abs use on the objective response rate (ORR) and immune-related adverse events (irAEs). The secondary outcomes were the effects of PPI and/or Abs use on progression-free survival (PFS) and overall survival (OS) after ICI therapy analyzed using the inverse probability of treatment weighting-adjusted Cox regression analysis. Results: Of the 155 patients enrolled in the study, 99 (64%) were PPI users and 56 (36%) Abs users. PPI users were associated with a significantly poorer ORR than non-PPI users (41% vs. 20%, respectively), whereas Abs use was not significantly associated with changes in ORR. The rate of irAEs was not significantly associated with the use of PPIs or Abs. Multivariate inverse probability of treatment weighting-adjusted Cox regression analysis revealed significantly poorer PFS and OS in PPI users than in non-PPI users, whereas Abs use was not associated with poorer outcomes. Conclusion: The concomitant use of PPI may adversely affect oncological outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with ICI therapy.