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To describe prostate-specific antigen (PSA) response and treatment adherence, overall and stratified by race, for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide.Electronic medical records representing 63 urology practices from the United States were used to conduct this study. Patients with ≥2 apalutamide prescription fills and ≥12 months of prior prostate cancer management were identified. Patients were followed from apalutamide initiation until a switch to another antineoplastic treatment, death, or end of data availability (October 4, 2019). PSA response (≥50% decline from baseline PSA) and apalutamide adherence rates are described for the overall nmCRPC population treated and also stratified by race (Black and non-Black cohorts).Overall, 193 patients with nmCRPC were initiated on apalutamide. Thirty-three patients were Black (17.1%), 138 were non-Black (71.5%), and the remaining had an unknown racial background. The mean baseline PSA level for the overall, Black, and non-Black cohorts, was 7.0 ng/mL, 10.5 ng/mL, and 5.6 ng/mL, respectively. At 12 months of follow-up, PSA response was 86.0%, 93.1%, and 85.9% for the overall, Black, and non-Black cohorts, respectively. During a mean follow-up period of 333 days, 352 days, and 326 days, adherence was 93.6%, 90.1%, and 94.5% for the overall, Black and non-Black cohorts, respectively.This real-world study of patients with nmCRPC initiated on apalutamide showed that PSA response was robust and consistent with clinical trial data. Moreover, both Black and non-Black patients demonstrated high treatment adherence.

Background The objective of this study was to evaluate differences in tolerability in patients with metastatic castration-resistant prostate cancer treated with enzalutamide (ENZA) or abiraterone acetate plus prednisone (AA+P). Patients and Methods This was a phase IV, prospective, open-label, multicenter, real-world study. Patients were prescribed ENZA or AA+P at the treating physician’s discretion. Computerized tests of 4 cognitive domains (Cogstate), patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-30], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-Fatigue], Functional Assessment of Cancer Therapy-Cognitive Function [FACT-Cog]), and patient/caregiver surveys were assessed at baseline and 2 months. Safety data were collected. Results Of 100 treated patients, 92 were evaluable (46/arm). Baseline characteristics were similar, with mild cognitive impairment observed in ∼20% of patients. The FACIT-Fatigue demonstrated a statistically significant worsening from baseline of −4.00 (95% confidence interval, −6.61 to −1.39) for ENZA compared with AA+P, −0.01 (95% confidence interval, −2.40 to 2.38). Overall, more adverse events (AEs) and more AEs of fatigue were reported with ENZA versus AA+P (52% vs. 36% and 26% vs. 8%, respectively). Grade 3/4 AEs were similar (4% vs. 6%). Unique neuropsychiatric AEs reported with ENZA included amnesia, cognitive disorders, memory impairment, and confusional state; those for AA+P included cerebrovascular accident, presyncope, and spinal cord compression. Clinically meaningful cognitive decline was seen in 4 patients on ENZA versus 1 patient on AA+P. However, the overall mean changes from baseline for the Cogstate tests, the EORTC QLQ-C30, and the FACT-Cog assessment were similar and showed no meaningful change. Caregiver survey responses noted more fatigue with ENZA and more moodiness with AA+P compared with patient responses. Conclusions Although baseline values were similar, more fatigue and neurocognitive differences were observed with ENZA compared with AA+P.

The authors assessed the use of distal third radius dual energy X-ray absorptiometry (DXA) concomitantly with central (hip and lumbar spine) DXA to identify men with osteopenia or osteoporosis receiving androgen deprivation therapy (ADT) for prostate cancer. Initial classification with central DXA demonstrated 60 (17%) normal, 187 (55%) osteopenic, and 96 (28%) osteoporotic patients. Sixteen of 60 (27%) normal patients were reclassified as osteopenic (14) or osteoporotic (2), and 20 of 187 (11%) osteopenic patients were reclassified as osteoporotic with the combination of central DXA plus distal third radius DXA. The difference in reclassification was statistically significant. The addition of distal third radius to central DXA scanning in men with bone loss associated with ADT identifies a statistically significant number of men being reclassified as having osteopenia or osteoporosis. Combined central and distal third radius DXA scanning should be considered routine in the evaluation of all men suspected of bone loss associated with ADT. This has specific significant clinical relevance because of the large number of men with nonevaluable central DXA studies. Fracture risk prediction and treatment recommendations based on this reclassification will need to be determined by follow-up studies.

Overactive bladder (OAB) syndrome is characterized by urinary frequency and urgency with or without urge incontinence, and often accompanied by nocturia. The prevalence of OAB increases with aging; it is a particularly common condition among the elderly, affecting at least 25% of people agedor = 65 years.The goal of this study was to assess the efficacy and tolerability of solifenacin 5 and 10 mg once daily for treating elderly subjects with OAB.This was a retrospective analysis of pooled data from 4 studies. Data were analyzed from elderly subjects (agedor = 65 years) with OAB who were treated with solifenacin in four 12-week, double-blind, Phase III, international, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled studies and from elderly subjects who received solifenacin in a 40-week, open-label, flexible-dose extension trial that enrolled subjects who completed 2 of the double-blind studies. Micturition data were collected from diaries completed during the 3 days before each study visit. Efficacy end points included mean change from baseline for the number of incontinence episodes/24 hours, urgency episodes/24 hours, number of micturitions/24 hours, and volume voided/micturition. The proportion of subjects who became continent or had no urgency episodes at end point was also evaluated.The mean age of the subjects in the 12-week, double-blind studies (N = 1045; 781 women, 264 men) was 71.9 years; mean age in the 40-week extension trial (N = 509; 359 women, 150 men) was 71.2 years. The majority of subjects (74.7% in the 12-week, double-blind studies and 70.5% in the 40-week extension trial) were female, and90% of the elderly subjects were white. The duration of OAB ranged from 0 to 66 months, and 43.7% had received previous medical therapy for OAB. The completion rate for elderly subjects was 85.5% for the 12-week, double-blind studies and 80.0% for the 40-week extension trial. Efficacy end points at week 12 of double-blind treatment demonstrated statistically significant improvements in the symptoms of OAB with solifenacin compared with placebo. Mean (SE) changes in number of incontinence episodes/24 hours were -1.5 (0.17) for the 5-mg dose and -1.9 (0.14) for the 10-mg dose compared with -1.0 (0.14) for placebo (P = 0.013 for the 5-mg dose and P0.001 for the 10-mg dose, vs placebo); mean (SE) changes in the number of urgency episodes/24 hours were -3.2 (0.27) for the 5-mg dose and -3.2 (0.19) for the 10-mg dose compared with -1.6 (0.18) for placebo (P0.001 for both doses vs placebo); mean (SE) changes in the number of micturitions/24 hours were -2.0 (0.17) for the 5-mg dose and -2.5 (0.13) for the 10-mg dose compared with -1.1 (0.13) for placebo (P0.001 for both doses vs placebo); mean (SE) changes in the volume voided/micturition were 30.2 (3.24) mL for the 5-mg dose and 46.2 (2.55) mL for the 10-mg dose, compared with 9.1 (2.39) mL for placebo (P0.001 for both doses vs placebo). The proportion of subjects with restoration of continence was 49.1% and 47.3% of the 5- and 10-mg treatment groups, respectively, compared with 28.9% of the placebo group (P0.001 for both doses vs placebo). The proportion of subjects with resolution of urgency was 34.6% and 24.9% for the 5- and 10-mg treatment groups, respectively, compared with 16.9% of the placebo group (P0.001 for the 5-mg dose and P0.01 for the 10-mg dose). Improvements in incontinence, urgency, and micturitions were maintained during the 40-week extension trial. The most common adverse events in both the double-blind and extension trials were dry mouth, constipation, and urinary tract infection. Most adverse events were mild to moderate in nature and did not result in treatment discontinuation.In these pooled analyses, solifenacin 5 and 10 mg once daily were efficacious and well tolerated in the treatment of these elderly subjects with OAB. Solifenacin therapy was also associated with a high level of persistence in a 40-week extension trial.

OBJECTIVES To evaluate whether the increased number of rectal perforations associated with contemporary transrectal ultrasound-guided, 12-core prostate biopsy, with a periprostatic block, is associated with a greater rate of postprocedural complications. METHODS We prospectively studied 1000 patients undergoing contemporary transrectal ultrasound-guided prostate biopsy and compared the rates of complicated urinary tract infection and significant rectal bleeding with the rates in our previous report of complications using a then-standard, 6-core biopsy technique, without a periprostatic block. RESULTS Three patients developed complicated urinary tract infections, two of which were with ciprofloxacin-resistant organisms. This was not a significant different statistically from our earlier report. Seven patients had significant rectal bleeding requiring endoscopic intervention. This rate also was not significantly different statistically from our earlier report. CONCLUSIONS Our infection and rectal bleeding complications associated with contemporary transrectal ultrasound-guided prostate biopsy were low. We experienced a small, nonstatistically significant, increase in the complicated urinary tract infection rate and a small, nonstatistically significant, increase in the rectal bleeding rate in association with the transition from an eight-core, no periprostatic block, technique to the contemporary technique.

Background In a phase 3, randomized, double-blinded (DB) trial (NCT00321620), subcutaneous (SC) denosumab prevented skeletal-related events (SRE) more effectively compared with intravenous (IV) zoledronic acid (ZA) in men with castration-resistant prostate cancer (CRPC) and bone metastases (Fizazi K et al., Lancet 2011). As a result, all patients (pts) remaining on study were offered open-label (OL) denosumab in a pre-specified 2-year extension phase. Materials and methods Pts (n = 1901) with CRPC metastatic to bone received either SC denosumab 120 mg and IV placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the DB treatment phase. OL denosumab Q4W was offered for up to 2 years to pts remaining on study. Pts declining OL treatment were followed for survival for up to 2 years after their last dose of investigational product in the DB treatment phase. Results Of 323 pts completing the DB phase, 153 (87.4%) who were randomized to denosumab (here referred to as DD pts) and 128 (86.5%) randomized to ZA (here referred to as ZD pts) continued in the OL phase. Demographics were balanced between groups. Cumulative median (Q1, Q3) denosumab exposure over the entire study for DD pts was 12.0 (5.6, 21.3) months (range: 0.1 to 67.2 months). Overall, adverse events (AEs) were comparable between groups (n = 138/147 [93.9%] DD pts; n = 105/118 [89.0%] ZD pts). Twelve pts in the DD group and 7 pts in the ZD group developed osteonecrosis of the jaw (ONJ) in the OL phase, resulting in a cumulative ONJ incidence for the entire study of 3.8% for DD pts and 2.2% for ZD pts. Hypocalcemia AEs during the OL phase were balanced between groups (n = 8 DD pts; n = 5 ZD pts). Serious AEs were reported in 78 (53.1%) DD pts and 63 (53.4%) ZD pts. Median (95% CI) overall survival over the entire study was similar between groups: 19.4 months (17.8 to 21.0) for DD pts, 19.3 months (18.0 to 20.6) for ZD pts. Conclusion This two-year OL extension treatment phase confirmed the long-term safety profile of denosumab in pts with prostate cancer metastatic to bone who received denosumab for up to 5.6 years or who switched from ZA to denosumab. Disclosure K. Fizazi: Consultant/advisor: Amgen, Novartis, J.E. Brown: Advisory Board Member: Amgen, Novartis, Bristol Myers Squibb Corporate Sponsored Research: Novartis Other Substantive Relationships: Consultant, Amgen, M. Carducci: Consultant/advisor: Amgen, N.D. Shore: Consultant/Advisor: Amgen, Astellas, Bayer, Dendreon, Janssen, Medivation, Sanofi Corporate Sponsored Research: Amgen, Astellas, Bayer, Dendreon, Janssen, Medivation, Sanofi, Active Biotech, BMS, Millenium, Oncogenix, Progenics, BN Immunotherapeutics, P. Sieber: Other substantive relationships: consultant, speaker: Amgen, R. Wei: Employee and stockholder: Amgen, C. Goessl: Employee and stockholder: Amgen. All other authors have declared no conflicts of interest.

Recent data indicates that the free-radical anion superoxide (O2-), an unstable cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel following reperfusion after low flow states. This report evaluates the effect of free radical scavengers on survival in an animal model with bowel ischemia. At laparotomy, the superior mesenteric artery (SMA) of 79 weanling rats (90 g) was occluded for one minute and released. Animals were divided into three experimental groups: group I acted as controls (n = 41), group II, received thiopental 5 mg/kg IV (n = 19), group III, received methohexital 2.5 mg/kg IV (n = 19). At one week animals were evaluated for mortality, mean survival time, evidence of bowel necrosis or perforation, and bowel appearance on scanning electron microscopy (EM). Mortality was 63.5% (26/41) in group I, 19 had necrotic bowel and 7 had gross perforation; 31.6% in group II (6/19) (p less than .05 versus control), with one necrotic bowel and 5 perforations; and 57.9% in group III (11/19) where 7 had necrotic bowel and 4 had perforations (p NS v control). Survival time (mean +/- SD in days) post SMA occlusion was 3.2 +/- 1.9 for group I; 4.0 +/- 1.7 for group II; and 2.5 +/- 2.0 for group III. EM showed mucosal destruction worsened by the duration of reperfusion, decreased by thiopental but not by methohexital. Thiopental, a free radical anion scavenger was cytoprotective in this animal model, as it decreased mortality and the incidence of bowel necrosis and perforation. These data support the thesis that following low flow states bowel ischemia may be related to a reperfusion injury due to the release of toxic free radical anions.

The role of acid phosphatase in the definition of response to treatment for prostate cancer is unclear. To better define its predictive value, especially regarding survival rate, we reviewed the clinical course of 76 men with Stage D2 prostate cancer who were treated with combination chemotherapy.