Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry.

PURPOSE: African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T. PATIENTS AND METHODS: OS for patients who received ≥1 sipuleucel-T infusion was compared between African American and Caucasian men using an all patient set and a baseline prostate-specific antigen (PSA)-matched set (two Caucasians to every one African American with baseline PSAs within 10% of each other). Univariable and multivariable analyses were conducted. Survival data were examined using Kaplan-Meier and Cox proportional hazard methodologies. RESULTS: Median follow-up was 46.6 months. Overall survival differed between African American and Caucasian men with hazard ratios (HR) of 0.81 (95% confidence interval [CI]: 0.68-0.97, P = 0.03) in the all patient set and 0.70 (95% CI: 0.57-0.86, P < 0.001) in the PSA-matched set. Median OS was longer in African Americans than in Caucasian men for both analysis sets, e.g., 35.3 and 25.8 months, respectively, in the PSA-matched set. Similar results were observed in the all patient set. Differences were larger when treatment began at lower baseline PSA; curves were more similar among patients with higher baseline PSA. In patients with baseline PSA below the median, the HR was 0.52 (95% CI: 0.37-0.72, P < 0.001), with median OS of 54.3 versus 33.4 months. Known prognostic factors and African American race (multivariable analyses; HR: 0.60, 95% CI: 0.48-0.74, P < 0.001) were independently associated with OS. Use of post-sipuleucel-T anticancer interventions was balanced between races. CONCLUSION: In this exploratory analysis of a registry including nearly 12% African American men with mCRPC, OS was significantly different between African Americans and Caucasians, indicating further research is warranted.

Low testosterone at first prostate-specific antigen failure and assessment of risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

BACKGROUND: Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein. METHODS: Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors. RESULTS: After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone. CONCLUSIONS: Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2018;124:1383-90. © 2017 American Cancer Society.

Physical and emotional health information needs and preferences of long-term prostate cancer survivors.

OBJECTIVE: Many men diagnosed with prostate cancer (PC) will experience physical and psychosocial late effects of treatment. Their interest/preferences for receiving information about addressing common sequelae is not well understood. We examined long-term PC survivors' level of interest, whether this differed based upon symptomatology, and their preferred coping information source. METHODS: N=615 PC survivors (3-8 years post-diagnosis) completed a survey on physical and psychological health and their information interests and preferences related to late effects of cancer treatment. RESULTS: Over half of PC survivors reported interest in information about late effects of treatment or sexual health, while approximately a quarter were interested in emotional health information. Survivors preferred to receive information about late effects of treatment from their oncologists, sexual health information from their primary care providers (PCP), oncologist, or written/online resources, and emotional health information from their PCP. Information needs were more commonly reported among men with poorer domain-specific health functioning. CONCLUSION: Long-term PC survivors report significant interest in receiving information about their physical, sexual, and emotional health. PRACTICE IMPLICATIONS: Medical providers caring for these men should inquire about survivors' information needs and future intervention efforts should consider who delivers the information, dependent upon the type of dysfunction reported.

Racial Differences in the Surgical Care of Medicare Beneficiaries With Localized Prostate Cancer.

IMPORTANCE: There is extensive evidence suggesting that black men with localized prostate cancer (PCa) have worse cancer-specific mortality compared with their non-Hispanic white counterparts. OBJECTIVE: To evaluate racial disparities in the use, quality of care, and outcomes of radical prostatectomy (RP) in elderly men (≥ 65 years) with nonmetastatic PCa. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis of outcomes stratified according to race (black vs non-Hispanic white) included 2020 elderly black patients (7.6%) and 24,462 elderly non-Hispanic white patients (92.4%) with localized PCa who underwent RP within the first year of PCa diagnosis in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2009. The study was performed in 2014. MAIN OUTCOMES AND MEASURES: Process of care (ie, time to treatment, lymph node dissection), as well as outcome measures (ie, complications, emergency department visits, readmissions, PCa-specific and all-cause mortality, costs) were evaluated using Cox proportional hazards regression. Multivariable conditional logistic regression and quantile regression were used to study the association of racial disparities with process of care and outcome measures. RESULTS: The proportion of black patients with localized prostate cancer who underwent RP within 90 days was 59.4% vs 69.5% of non-Hispanic white patients (P < 001). In quantile regression of the top 50% of patients, blacks had a 7-day treatment delay compared with non-Hispanic whites. (P < 001). Black patients were less likely to undergo lymph node dissection (odds ratio [OR], 0.76 [95% CI, 0.66-0.80]; P < .001) but had higher odds of postoperative visits to the emergency department (within 30 days: OR, 1.48 [95% CI, 1.18-1.86]); after 30 days or more (OR, 1.45 [95% CI, 1.19-1.76]) and readmissions (within 30 days: OR, 1.28 [95% CI, 1.02-1.61]); ≥ 30 days (OR, 1.27 [95% CI, 1.07-1.51]) compared with non-Hispanic whites. The surgical treatment of black patients was associated with a higher incremental annual cost (the top 50% of blacks spent $1185.50 (95% CI , $804.85-1 $1566.10; P < .001) more than the top 50% of non-Hispanic whites). There was no difference in PCa-specific mortality (P = .16) or all-cause mortality (P = .64) between black and non-Hispanic white men. CONCLUSIONS AND RELEVANCE: Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared with non-Hispanic white men; however, this does not translate into a difference in PCa-specific or all-cause mortality.

The Development of Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP).

New systemic therapies have prolonged the lives of men with metastatic castration-resistant prostate cancer (mCRPC). Use of these therapies in the adjuvant setting when the disease may be micrometastatic and potentially more sensitive to therapies may decrease mortality from prostate cancer. However, the conduct of adjuvant prostate cancer clinical trials is hampered by taking longer than a decade to reach the meaningful endpoint of overall survival (OS) and the fact that many men never die from prostate cancer, even if they relapse. A validated intermediate clinical endpoint (ICE) in prostate cancer that is a robust surrogate for OS has yet to be defined. This paper details the plans, process, and progress of the international Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group to pool individual patient data from all available clinical trials of radiation or prostatectomy for localized disease and conduct the requisite analyses to determine whether an ICE can be identified. This paper further details the challenges and the a priori statistical analytical plans and strategies to define an ICE for adjuvant prostate cancer clinical trials. In addition, a brief review of the health economic analyses to model the benefits to patients, society and manufacturers is detailed. If successful, the results from this work will provide a robust surrogate for OS that will expedite the design and conduct of future adjuvant therapy trials using new agents that have proven activity in mCRPC. Moreover, it will also define the health economic benefits to patients and societies.

Observation versus initial treatment for men with localized, low-risk prostate cancer: a cost-effectiveness analysis.

BACKGROUND: Observation is underutilized among men with localized, low-risk prostate cancer. OBJECTIVE: To assess the costs and benefits of observation versus initial treatment. DESIGN: Decision analysis simulating treatment or observation. DATA SOURCES: Medicare schedules, published literature. TARGET POPULATION: Men aged 65 and 75 years who had newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 µg/L, stage ≤T2a, Gleason score ≤3 + 3). TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). OUTCOME MEASURES: Quality-adjusted life expectancy and costs. RESULTS OF BASE-CASE ANALYSIS: Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15,374 ($24,520 vs. $39,894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11,746 ($18,302 vs. $30,048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. RESULTS OF SENSITIVITY ANALYSIS: Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. LIMITATION: Results depend on outcomes reported in the published literature, which is limited. CONCLUSION: Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. PRIMARY FUNDING SOURCE: National Cancer Institute, U.S. Department of Defense, Prostate Cancer Foundation, and Institute for Clinical and Economic Review.

Active surveillance compared with initial treatment for men with low-risk prostate cancer: a decision analysis.

CONTEXT: In the United States, 192,000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized. OBJECTIVE: To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. DESIGN AND SETTING: Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment. PATIENTS: Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6). MAIN OUTCOME MEASURE: Quality-adjusted life expectancy (QALE). RESULTS: Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. CONCLUSIONS: Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.

Department of Defense prostate cancer clinical trials consortium: a new instrument for prostate cancer clinical research.

BACKGROUND: In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). PATIENTS AND METHODS: The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >or=1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. RESULTS: The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. CONCLUSION: The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.

A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones.

OBJECTIVE: To evaluate mifepristone (RU-486) in patients with castration-resistant prostate cancer (CRPC), with a correlative assessment of serum androgens and androgen metabolites PATIENTS AND METHODS: The androgen receptor (AR) is critical in the development and progression of prostate cancer, but available antiandrogens incompletely abrogate AR signalling. Mifepristone is a potent AR antagonist that functions by competing with androgen, preventing AR coactivator binding and by enhancing binding of AR corepressors. Patients with CRPC were treated with mifepristone 200 mg/day oral until disease progression. Testosterone, dihydrotestosterone (DHT), androstenedione, dihydroepiandrosterone sulphate and the testosterone metabolite 3 alpha-diol G, were measured at baseline and during therapy. RESULTS: Nineteen patients were enrolled between April and August 2005; they were treated for a median (range) of 85 (31-338) days. The median prostate-specific antigen (PSA) level at enrollment was 22.0 (3.0-937.2) ng/mL. No patient had a PSA response (>50% reduction in PSA). Six patients had stable disease for a median of 5.5 months. After 1 month, adrenal androgens were increased and testosterone and DHT increased by 91% and 80%, respectively, compared to baseline. CONCLUSION: Mifepristone had limited activity in patients with CRPC, and stimulated a marked increase in adrenal androgens, testosterone and DHT. We hypothesise that inhibition of glucocorticoid receptor by mifepristone resulted in an increase in adrenocorticotropic hormone and subsequent increase in adrenal androgens, and that their conversion by tumour cells to testosterone and DHT probably limited the efficacy of mifepristone. These data emphasize the continued importance of alternative androgen sources in AR signalling in CRPC.

Contemporary trends in low risk prostate cancer: risk assessment and treatment.

PURPOSE: We updated national risk trends in prostate cancer with a focus on low risk tumors, reexamined trends in primary treatment for low risk tumors and substratified patients at low risk based on pretreatment clinical data. MATERIALS AND METHODS: Data were abstracted from the CaPSURE registry. A total of 10,385 men were diagnosed between 1990 and 2006 with localized disease. Low risk was defined as prostate specific antigen 10 ng/ml or less, Gleason score 6 or less and clinical T stage 2a or less. Temporal trends were assessed for patient distribution among risk groups and in the low risk group for individual risk factors, Kattan nomogram prediction, Cancer of the Prostate Risk Assessment score and primary treatment. The ability of the Cancer of the Prostate Risk Assessment score to substratify low risk prostatectomy cases was evaluated with survival analysis. RESULTS: The proportion of low risk tumors in CaPSURE almost doubled from 27.5% in 1990 to 1994, to 46.4% in 2000 to 2001 but it has been relatively constant since then. A growing proportion of low risk tumors are cT1c and virtually all are Gleason score 6. Prostate specific antigen and the percent of positive biopsies decreased throughout the study period, as did the mean Cancer of the Prostate Risk Assessment score. The use of active surveillance increased from a nadir of 6.2% in 2000 to 2001, to 10.2% in 2004 to 2006. The use of prostatectomy also increased, whereas the use of androgen deprivation and radiation decreased. The likelihood of recurrence increased significantly with increasing Cancer of the Prostate Risk Assessment scores. CONCLUSIONS: Patients at low risk can be further substratified to identify those at very low risk based on clinical variables. The use of surveillance is increasing but overtreatment remains a concern in these patients.

Racial differences in screening for prostate cancer in the elderly.

BACKGROUND: Black men are more likely than white men to be diagnosed as having advanced prostate cancer, and their prostate cancer mortality rates are more than twice as high. Low screening rates among black men may contribute to these disparities, but there are few data on racial differences in prostate cancer screening. OBJECTIVES: To present a case-control study of racial differences in the use of prostate-specific antigen (PSA) as a screening test among Medicare beneficiaries in New Jersey and to assess the degree to which race is associated with prostate cancer screening. METHODS: The study used a statewide database of claims data from Medicare Parts A and B, Medicaid, and the state's Pharmaceutical Assistance for the Aged and Disabled program. Prevalent cases of prostate cancer were excluded using the state's cancer registry. Of 139 672 men who underwent PSA screening, 34 984 were randomly selected along with an identical number of controls matched by month and year of birth. After men with International Classification of Diseases, Ninth Revision, Clinical Modification,or Current Procedural Terminology codes indicative of prostate cancer were excluded, 33 463 case patients and 33 782 control subjects remained. RESULTS: The use of PSA screening was strongly and inversely associated with black race (odds ratio [OR] = 0.50; P<.001), poverty (OR = 0.33; P<.001), and near poverty (OR = 0.69; P<.001). Multivariate logistic regression analysis after age, socioeconomic status, comorbidity, and use of health care services were controlled for revealed that black race remained a strong predictor of not undergoing PSA screening (OR = 0.65; 95% confidence interval, 0.60-0.70). CONCLUSIONS: Elderly blacks are substantially less likely to undergo PSA screening than elderly whites. Differences in socioeconomic status and comorbid conditions explain only a small part of the racial differences in screening rates.