Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BACKGROUND: The large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). METHODS: PROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal. RESULTS: In 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively. CONCLUSIONS: PROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings.

Treatment Duration, Healthcare Resource Utilization, and Costs Among Chemotherapy-Naïve Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate: A Retrospective Claims Analysis.

INTRODUCTION: Enzalutamide and abiraterone acetate (plus prednisone) are new hormonal treatments for metastatic castration-resistant prostate cancer (mCRPC). This study compared treatment duration, healthcare resource utilization (HRU), and treatment costs for chemotherapy-naïve mCRPC patients treated with enzalutamide or abiraterone acetate in the USA. METHODS: Chemotherapy-naïve mCRPC patients initiating treatment with enzalutamide or abiraterone acetate were identified from administrative claims. Continuous enrollment ≥ 6 months before and ≥ 3 months after the index date (initiation date of enzalutamide or abiraterone acetate) was required. Treatment duration, all-cause and prostate cancer-related HRU, and costs were estimated during the post-index period. Multivariable analyses compared HRU and costs between cohorts, adjusting for baseline characteristics. RESULTS: Overall, 920 chemotherapy-naïve patients initiated enzalutamide and 2310 initiated abiraterone acetate (median follow-up, 10.7 and 13.5 months, respectively). More enzalutamide-treated patients had corticosteroid-sensitive comorbidities at baseline. Treatment duration was longer with enzalutamide versus abiraterone acetate (median, 10.7 vs. 8.8 months; P = 0.008). Enzalutamide was associated with fewer all-cause inpatient admissions [adjusted incidence rate ratio (95% confidence interval) 0.87 (0.76, 0.99)], days of hospitalization [0.84 (0.70, 1.02)], and outpatient visits [0.94 (0.90, 0.98)], and fewer prostate cancer-related outpatient visits [0.92 (0.87, 0.96)] compared with abiraterone acetate. Enzalutamide was also associated with lower prostate cancer-related inpatient and emergency department costs [adjusted differences, $122 (P = 0.024) and $28 (P = 0.009), respectively]. CONCLUSION: Chemotherapy-naïve mCRPC patients treated with enzalutamide versus abiraterone acetate had longer treatment duration and incurred lower HRU and prostate cancer-related inpatient and emergency department costs. FUNDING: Astellas Pharma Inc.

Integrating the Genomic Prostate Score into Clinical Practice Workflow.

INTRODUCTION: A dilemma that urologists face is how to determine which patients with prostate cancer need immediate intervention and which patients can be safely placed on active surveillance. Gene expression profile analysis of biopsy tissue has been proposed as a means of providing more accurate risk stratification for low risk prostate cancer. However, there is a general lack of acceptance and standardization around the integration of genomic testing in clinical practice. The Oncotype DX® prostate cancer assay is a commercially available tissue based assay that assesses the expression of key genes across multiple biological pathways predictive of prostate cancer aggressiveness from the diagnostic biopsy specimen, and reports an individual Genomic Prostate Score. METHODS: With the recommendations set forth in this article we aim to standardize operational best practices for the integration of the Genomic Prostate Score into clinical practice. Its purpose is to provide practical guidance to help physicians understand, run, interpret and communicate actionable results to patients. RESULTS: The Genomic Prostate Score reflects the biology of the underlying tumor to help guide initial treatment decisions at the time of biopsy. This article is based on real-world evidence from the authors' respective experiences at their institutions and practices. The authors were carefully selected based on their depth of experience and knowledge about the Genomic Prostate Score and, as such, it is their expertise that is being leveraged to support the best practices algorithm. CONCLUSIONS: This article provides easy to use, clear-cut and practical guidance for physicians on how to use the Genomic Prostate Score to inform decisions regarding active surveillance.

Surveillance for recurrent bladder cancer using a point-of-care proteomic assay.

CONTEXT: At least 50% of patients with a history of bladder cancer have recurrences, so rigorous surveillance is necessary. Cystoscopy is standard but can fail to detect some bladder cancers, so a urine test is frequently part of the evaluation. OBJECTIVE: To investigate whether a point-of-care proteomic test that measures the nuclear matrix protein NMP22 in voided urine could improve detection of recurrence during monitoring of patients with a history of bladder cancer. DESIGN, SETTING, AND PATIENTS: From September 2001 to February 2002, 23 academic, private practice, and hospital facilities in 9 US states prospectively enrolled 668 consecutive patients with a history of bladder cancer in this cross-sectional study. Patients provided a voided urine sample for analysis of NMP22 protein and cytology prior to cystoscopy. MAIN OUTCOME MEASURES: Diagnosis of bladder cancer recurrence, based on cystoscopy with biopsy, was accepted as the reference standard. The performance of the NMP22 test was compared with voided urine cytology as an aid to detection. Testing for the NMP22 tumor marker was conducted in a blinded manner. RESULTS: Bladder cancer was diagnosed in 103 patients. Cystoscopy alone identified 91.3% of the cancers (94/103; 95% confidence interval [CI], 84.1%-95.9%). The combination of cystoscopy with the NMP22 assay detected 99.0% of the malignancies (102/103; 95% CI, 94.7%-100%; P = .005). The NMP22 assay detected 8 of 9 cancers that were not visualized during initial cystoscopy, including 7 that were high-grade. The sensitivity and specificity of the NMP22 test alone were 49.5% (51/103; 95% CI, 39.5%-59.5%) and 87.3% (493/565; 95% CI, 84.2%-89.9%), respectively. Voided cytology detected only 3 of the malignancies missed during initial cystoscopy and did not significantly increase the sensitivity of cystoscopy (94.2%; 95% CI, 87.7%-97.8%; P = .08). CONCLUSION: The noninvasive point-of-care assay for elevated urinary NMP22 protein can increase the ability to detect recurrent bladder cancer, with test results available during the patient visit.

Sexual function in patients treated for benign prostatic hyperplasia.

CONTEXT: What is the effect of different treatment options for benign prostatic hyperplasia (BPH) on sexual function or dysfunction? With increasing age, sexual dysfunction and BPH become more prevalent. Some treatments for BPH can affect sexual function. Different surgical treatments have different effects on sexual function depending on how much the internal involuntary sphincter is affected. The same is true for medical therapies, each class of drug having a unique affect on sexual function. STARTING POINT: In the past, many articles suggested a causal relation between BPH and sexual dysfunction. But a recent report by H Leliefeld and colleagues (BJU International 2002; 89: 208-13) confirms the idea that the relation is coincidental. Prospectively, these investigators examined patients at baseline and 9 months after various treatments for BPH with questionnaires on voiding symptoms, related complications, and sexual function. 84% of patients reported no change in sexual function. All treatments showed both improvement and deterioration in 3-14% and 0-16% of patients, respectively. As expected, age was the most important determinant of sexual function. In addition, the effect of severe irritative symptoms or the presence of urological comorbidity, such as bladder stones, increased the rate of sexual dysfunction. In this study, most patients underwent surgical therapy or watchful waiting while fewer had medical therapy. Too few patients had minimally invasive procedures to comment on their effect on sexual function. WHRE NEXT? Thus the relation between treatment of BPH (or watchful waiting) and sexual dysfunction is usually coincidental, unless symptoms become severe or complications (such as bladder stones or urinary retention) develop. More prospective studies are needed to assess the effect of BPH and its treatment on sexual function. Medical therapy is now more common than surgery in developed countries and treatment of BPH is commonly advocated for improvement in quality of life. Therefore any effects on sexual function become even more important. As minimally invasive surgical operations become more common, more data will be required for such interventions. The difficulty will be in keeping up with the rapidly evolving techniques of minimally invasive therapies.

Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.

Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.