Higher Baseline Prostate-specific Antigen Research Articles

Very Long-Term Complete Remission Can Be Achieved in Men With High-Risk Localized Prostate Cancer and a Very High PSA Value: An Analysis of the GETUG 12 Phase 3 Trial.

Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established. Ancillary analysis from the GETUG 12 phase 3 trial. Patients with non-metastatic high-risk prostate cancer by bone and computerized tomography (CT) scan were randomly assigned to receive androgen deprivation therapy (ADT) and docetaxel plus estramustine or ADT alone. Relapse-free survival (RFS), clinical RFS, metastases-free survival (MFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using the Kaplan-Meier method for different levels of PSA (50 ng/mL, 75 ng/mL, and 100 ng/mL). The relationship between PSA and outcomes was studied using residual-based approaches and spline functions. The median follow-up was 12 years (range: 0-15.3). Baseline PSA (<50 ng/mL, n=328; ≥50ng/mL, n=85) was associated with improved RFS (P=.0005), cRFS (P=.0024), and MFS (P=.0068). The 12-year RFS rate was 46.33% (CI 40.59-51.86), 33.59% (CI 22.55-44.97), and 11.76% (1.96-31.20) in men with PSA values <50 ng/mL (n=328), 50-100 ng/mL (n=68), and ≥100 ng/mL (n=17), respectively. Exploratory analyses revealed no deviation from the linear relationship assumption between PSA and the log hazard of events. Men with apparently localized prostate cancer and a high baseline PSA value have a reasonable chance of being long-term disease-free when treated with curative intent combining systemic and local therapy.

Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial.

This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer. PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and P values were based on an unstratified Cox proportional analysis model. In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively. There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer.

Nonmetastatic castration-resistant prostate cancer: Novel agents to treat a lethal disease

Nonmetastatic castration-resistant prostate cancer (nmCRPC) - defined as prostate-specific antigen (PSA) > 2 ng/mL, testosterone castration levels < 1.7 nm/L, and the absence of metastatic lesions on conventional imaging (computed tomography or bone scan) - has been defined as a lethal disease by the Prostate Cancer Work Group. One-third of patients with prostate cancer who receive androgen deprivation therapy for biochemical recurrence after local treatment will develop CRPC, with death occurring an average of 2.5 years after diagnosis of castration resistance. Most patients diagnosed with nmCRPC are asymptomatic or minimally symptomatic at diagnosis due to local treatment. In patients with short PSA doubling times (< 10 mo) and high baseline PSA levels, there is a high risk of bone metastases followed by prostate cancer-related mortality. These patients also present significant morbidity that negatively impacts quality of life (QoL). Recently, the results of three randomized trials (PROSPER, SPARTAN, and ARAMIS) were published. Those trials evaluated the efficacy of three different androgen receptor inhibitors - enzalutamide, apalutamide, and darolutamide - in patients with nmCRPC. In all three trials, the study drugs improved both metastasis-free survival and overall survival compared to placebo, plus on-going androgen deprivation therapy without a negative impact on QoL. In patients with nmCRPC, the most important clinical objective is early detection and treatment to maintain a low tumor burden and to prolong the symptom-free interval. For patients with nmCRPC, these novel drugs offer new hope for better QoL and survival outcomes.

Upgrading on radical prostatectomy specimens of very low- and low-risk prostate cancer patients on active surveillance: A population-level analysis.

A proportion of prostate cancer (PCa) patients initially managed with active surveillance (AS) are upgraded to a higher Gleason score (GS) at the time of radical prostatectomy (RP). Our objective was to determine predictors of upgrading on RP specimens using a national database. The Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database was used to identify AS patients diagnosed with very low- or low-risk PCa who underwent delayed RP between 2010 and 2015. The primary outcome was upgrading to GS 7 disease or worse. Logistic regression analyses were used to evaluate demographic and oncological predictors of upgrading on final specimen. A total of 3775 men underwent RP after a period of AS, 3541 (93.8%) of whom were cT2a; 792 (21.0%) patients were upgraded on RP specimen, with 85.4%, 10.6%, and 3.4% upgraded to GS 7(3+4), 7(4+3), and 8 diseases, respectively. On multivariable analysis, higher prostate-specific antigen (PSA) at diagnosis (5-10 vs. 0-2 ng/ml, odd ratio [OR] 2.59, p<0.001) and percent core involvement (80-100% vs. 0-20%, OR 2.52, p=0.003) were significant predictors of upgrading on final RP specimen, whereas higher socioeconomic status predicted lower odds of upgrading (highest vs. lowest quartile OR 0.75, p=0.013). Higher baseline PSA and percent positive cores involvement are associated with significantly increased risk of upgrading on RP after AS, whereas higher socioeconomic status predicts lower odds of such events. These results may help identify patients at increased risk of adverse pathology on final specimen who may benefit from earlier definitive treatment.

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

PurposeAfrican 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 methodsOS 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.ResultsMedian 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.ConclusionIn 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.

225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience.

Up to 30% of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) never respond or develop resistance to 177Lu-labeled PSMA-targeted radioligand monotherapy. Single-agent PSMA-targeted radioligand therapy (PRLT) with the alpha-emitter 225Ac showed promise against mCRPC but may cause severe and/or persistent xerostomia, which may substantially impair patients' quality-of-life. We hypothesized that when 177Lu-PSMA ligand alone is ineffective, tandem therapy with low-activity 225Ac-PSMA ligand plus full activity of the beta emitter may enhance efficacy while minimizing xerostomia severity. We retrospectively analyzed pilot experience with 1 course of 225Ac-PSMA-617/177Lu-PSMA-617 tandem therapy in our first 20 patients with mCRPC receiving this intervention after insufficiently responding to 177Lu-PSMA-617 monotherapy. This cohort had late-stage/end-stage disease with high baseline prostate-specific antigen (PSA) concentration (median 215 ng/mL), heavy pre-treatment (abiraterone and/or enzalutamide, and 177Lu-PRLT [median cumulative activity, 26.3 GBq] in 20/20 patients, 100%; docetaxel and/or cabazitaxel in 13/20 patients, 65%), and frequent Eastern Cooperative Oncology Group performance status of 2 (8/20 patients, 40%). Median (minimum-maximum) administered activities were 225Ac-PSMA-617, 5.3 (1.5-7.9) MBq, and 177Lu-PSMA-617, 6.9 (5.0-11.6) GBq. Significant responders to tandem therapy received 177Lu-PSMA-617 monotherapy as maintenance (median [minimum-maximum]: 1 [0-5] cycle). After a median (minimum-maximum) 22 (14-63) weeks' follow-up, 13/20 patients (65%) had as best biochemical response a PSA decline > 50%. Median (95% confidence interval) progression-free survival was 19 (12-26) weeks, and overall survival was 48 (4-92) weeks post-tandem therapy administration. Xerostomia was reported as grade 1 (very mild) in 8/20 patients (40%), grade 2 (mild) in 5/20 (25%), and grade 3/4 in 0/20. Our results suggest that a single course of tandem therapy with low-activity 225Ac-PSMA-617/full-activity 177Lu-PSMA-617 may safely enhance response to PRLT in men with late-stage/end-stage mCRPC while minimizing xerostomia severity. Formal study of this combination is warranted.

Population-Based Analysis Of The Use Of Radium-223 For Bone-Metastatic Castration-Resistant Prostate Cancer In Ontario, And Of Factors Associated With Treatment Completion And Outcome.

IntroductionRadium-223 (Ra223) prolongs the survival and improves the quality of life of men with metastatic, castration-resistant prostate cancer (mCRPC) to bones. However, compared to other mCRPC therapies, using Ra223 comes with its unique challenges. Hence, we aimed to identify Ra223 utilization patterns under real-world conditions, as well as factors predicting treatment completion and outcome.MethodsIn this retrospective chart analysis, 198 mCRPC patients were identified that had received Ra223 outside of clinical trials or access programs from January 2015 to October 2016 at four cancer centres in Ontario. The main outcomes studied were Ra223 completion rate, reasons for early treatment discontinuation, overall survival, and survival differences in patients completing Ra223 therapy versus patients receiving <6 cycles of Ra223. In addition, patient and disease characteristics were analysed to identify predictors of treatment completion and survival.ResultsIn this cohort of patients mostly pretreated with abiraterone and/or enzalutamide (92.4%), almost half of which had also received docetaxel (48.5%), the Ra223 completion rate was 46.5%, and the actuarial median survival was 13.3 months. The main reason for early Ra223 discontinuation was disease progression, and Ra223 non-completion was associated with poorer outcome (median survival 8.1 months [6.0–12.2] versus 18.7 months [15.3–22.3] in men completing Ra223, p<0.0001). Lymph node metastases and a high baseline prostate-specific antigen (PSA) were independent predictors of early treatment discontinuation. Multivariable Cox proportional hazards models revealed early Ra223 discontinuation, baseline anemia, high PSA, prior skeletal-related events, visceral metastases, and being referred to another centre for Ra223 therapy as predictors of worse outcome.ConclusionDespite a lower completion rate than observed under clinical trial conditions, the real-world results achieved with Ra223 are encouraging. If prospectively validated, predictive patient and disease characteristics identified in our cohort might become instrumental to identify mCRPC patients likely to complete and to most benefit from Ra223 therapy.

Hemigland Cryoablation of Localized Low, Intermediate and High Risk Prostate Cancer: Oncologic and Functional Outcomes at 5 Years.

We evaluated 5-year oncologic and functional outcomes of hemigland cryoablation of localized prostate cancer. We reviewed the records of 160 consecutive men who underwent hemigland cryoablation of localized prostate cancer. Recurrent and/or residual clinically significant prostate cancer was defined as Grade Group 2 or greater on followup biopsy. A prostate specific antigen nadir plus 2 ng/ml according to the Phoenix criteria was used to define biochemical failure. Radical treatment was defined as any whole gland therapy. Treatment failure was defined as any radical and/or whole gland treatment, systemic therapy initiation, metastasis or prostate cancer specific mortality. The study primary end point was treatment failure-free survival. The secondary end points were survival free of biochemical failure, clinically significant prostate cancer and radical treatment. Followup biopsy and functional outcomes were also evaluated. Statistical analysis included the Kaplan-Meier method, and univariate and multivariable Cox and logistic regression with significance considered at p <0.05. Median patient age was 67 years, baseline prostate specific antigen was 6.3 ng/ml and followup was 40 months. A total of 131 patients (82%) had D'Amico intermediate (66%) or high risk (16%) prostate cancer. At 5 years the treatment failure-free survival rate was 85%, the biochemical failure-free survival rate was 62% and the survival rate free of clinically significant prostate cancer was 89%. Higher baseline prostate specific antigen independently predicted treatment failure (p <0.001), biochemical failure (p=0.048), recurrence and radical treatment (p <0.01). Grade Group 3 or greater independently predicted treatment failure (p=0.04). The metastasis-free survival rate was 100% at 5 years. Pad-free continence and potency (erections sufficient for intercourse) were retained in 97% and 73% of patients, respectively. There was no rectal fistula or mortality. Hemigland cryoablation of localized prostate cancer provides effective midterm oncologic outcomes with good continence and potency. Patients with higher baseline prostate specific antigen are at increased risk for biochemical failure, recurrent cancer and treatment failure.

Experience with sipuleucel-T in metastatic castration-resistant prostate cancer (mCRPC) with visceral spread from PROCEED.

174 Background: Trials of approved agents in mCRPC have reported shorter overall survival (OS) in men with visceral metastases (mets). The phase 3 IMPACT trial evaluated sipuleucel-T, an autologous cellular immunotherapy, in mCRPC but excluded visceral mets. PROCEED, a registry of mCRPC patients receiving sipuleucel-T, offers the first description of sipuleucel-T in patients with visceral mets. Methods: PROCEED enrolled men with mCRPC treated with sipuleucel-T biweekly x 3. Dose adjustment for organ dysfunction was unnecessary. Men were followed until death, study withdrawal, or a minimum of 3 years. OS is reported in this post-hoc subgroup analysis. Results: 1902 men received ≥1 sipuleucel-T infusion between 2011-2014. Visceral mets (n = 90) included liver (n=21), lung (n=61), and brain (n=2) involvement. Compared to patients without visceral mets (Table), men with visceral mets had poorer performance status (PS) and higher baseline prostate-specific antigen (PSA). Median OS was 20.5 and 31.2 mo in those with and without visceral mets. Patients with liver and lung mets had a median OS of 16.3 and 21.0 mo, respectively. Activation of antigen-presenting cells, a measure of immune activation and product potency, was similar in those with and without visceral mets. Conclusions: Initial observations suggest that patients with mCRPC and visceral spread can activate their immune cells to produce sipuleucel-T, but have a shorter OS than those with bone and/or lymph node spread. (NCT01306890). Clinical trial information: NCT00065442. [Table: see text]

Rethinking active surveillance for prostate cancer in African American men

Active surveillance (AS) is a treatment modality for prostate cancer that aims to simultaneously avoid overtreatment and allow for the timely intervention of localized disease. AS has become the de facto standard of care for most men with low-risk prostate cancer. However, few African American (AA) men were included in the prospective observational cohorts that resulted in a paradigm shift in treatment recommendations from active intervention toward AS. It has been established that AA men have an increased prostate cancer incidence, higher baseline prostate-specific antigen (PSA) values, more aggressive prostate cancer features, greater frequency of biochemical recurrence after treatment, and higher overall cancer-specific mortality compared to their Caucasian counterparts. As such, this has given many physicians pause before initiating AS for AA patients. In the following manuscript, we will review the available literature regarding AS, with a particular focus on AA men. The preponderance of evidence demonstrates that AS is as viable a management method for AA with low-risk prostate cancer as it is with other racial groups.

The Relationship of Baseline Prostate Specific Antigen and Risk of Future Prostate Cancer and Its Variance by Race

PurposeSeveral studies suggest that a baseline prostate specific antigen (PSA) measured in young men predicts future risk of prostate cancer. Considering recent recommendations against PSA screening, high-risk populations (e.g. black men, men with a high baseline PSA) may be particularly vulnerable in the coming years. Thus, we investigated the relationship between baseline PSA and future prostate cancer in a black majority–minority urban population. Materials and methodsA retrospective analysis was performed of the prostate biopsy database (n = 994) at the Brooklyn Veterans Affairs Hospital. These men were referred to urology clinic for elevated PSA and biopsied between 2007 and 2014. Multivariate logistic regression was used to predict positive prostate biopsy from log-transformed baseline PSA, race (black, white, or other), and several other variables. ResultsThe majority of men identified as black (50.2%). Median age at time of baseline PSA and biopsy was 58.6 and 64.8, respectively. Median baseline PSA was similar among black men and white men (2.70 vs 2.91 for black men vs white men, p = 0.232). Even so, black men were more likely than white men to be diagnosed with prostate cancer (OR 1.62, p < 0.0001). Black men less than age 70 were at particularly greater risk than their white counterparts. Baseline PSA was not a statistically significant predictor of future prostate cancer (p = 0.101). ConclusionsBlack men were more likely to be diagnosed with prostate cancer than were white men, despite comparable baseline PSA. In our pre-screened population at the urology clinic, a retrospective examination of baseline PSA did not predict future prostate cancer.

Exploring the Clinical Benefit of Docetaxel or Enzalutamide After Disease Progression During Abiraterone Acetate and Prednisone Treatment in Men With Metastatic Castration-Resistant Prostate Cancer

BackgroundAbiraterone acetate (AA) has demonstrated improved outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). However, data are lacking on the effect of AA on subsequent efficacy of enzalutamide or docetaxel. Patients and MethodsWe included men with mCRPC who received AA and subsequent enzalutamide or docetaxel by August 12, 2013. Patients were separated into 3 groups: group A, treated with AA then enzalutamide before chemotherapy; group B, treated with AA then docetaxel; and group C, treated with AA and enzalutamide after chemotherapy. The primary objective was to describe the response and overall survival with subsequent therapy. ResultsThere were 28 evaluable patients who received enzalutamide after AA (9 in group A and 19 in group C) and 13 patients who received docetaxel after AA (group B). Group A patients had more visceral disease and higher baseline prostate-specific antigen (PSA) levels, and group C men had a higher level of pain and multiple poor prognostic features. Median progression-free survival was 3.6, 5.1, and 2.8 months, respectively, and median overall survival was 8.5, not reached, and 9.6 months, respectively. A ≥ 50% PSA decline was achieved in 11%, 63%, and 5% of group A, B, and C patients, respectively. Radiographic or clinical progression as best response was noted in 55.5%, 30.8%, and 68.4% in each respective group. ConclusionIn this chart review of consecutive men with progressive mCRPC after AA, we found modest activity for enzalutamide and docetaxel, with clear cross-resistance for AA and enzalutamide. These data might inform the complex treatment decisions after AA treatment.

Men (Aged 40-49 Years) With a Single Baseline Prostate-specific Antigen Below 1.0 ng/mL Have a Very Low Long-term Risk of Prostate Cancer: Results From a Prospectively Screened Population Cohort

To study the use of a baseline prostate-specific antigen (PSA) and digital rectal examination in men (aged 40-49 years) in predicting long-term prostate cancer risk in a prospectively followed, representative population cohort. Since 1990, a random sample of men in Olmsted County (aged 40-49 years) has been followed up prospectively (n = 268), with biennial visits, including a urologic questionnaire, PSA screening, and physical examination. The ensuing risk of prostate cancer (CaP) was compared using survival analyses. Median follow-up was 16.3 years (interquartile range 14.0-17.3, max 19.1). For men with a baseline PSA <1.0 ng/mL (n = 195), the risk of subsequent Gleason 6 CaP diagnosis by 55 years was 0.6% (95% confidence interval [CI] 0%-1.7%) and 15.7% (95% CI 6.5%-24.9%) for men with a baseline PSA ≥ 1.0 ng/mL. No man with a low baseline PSA developed an intermediate or high risk CaP, whereas 2.6% of men with a higher baseline PSA did (95% CI 0.58%-4.6%). Men (aged 40-49 years) can be stratified with a baseline PSA. If it is below 1.0 ng/mL, there is very little risk for developing a lethal CaP, and as many as 75% of men might be able to avoid additional PSA screening until 55 years. Conversely, men aged 40-49 years with a baseline PSA level >1.0 ng/mL had a significant risk of CaP diagnosis and should be monitored more closely.

Increased expression of Golgi phosphoprotein-3 is associated with tumor aggressiveness and poor prognosis of prostate cancer

BackgroundTo investigate the expression of Golgi phosphoprotein-3 (GOLPH3) in prostate cancer and determine its prognostic value.MethodsImmunohistochemical staining for GOLPH3 was performed on tissue microarrays of 342 prostate patients. The correlation between GOLPH3 expression with its clinicopathologic factors was also analyzed in order to determine its prognostic significance.ResultsGOLPH3 expression of normal prostate tissues, benign prostate hyperplasia, high-grade prostatic intraepithelial neoplasia, and hormone-dependent prostate cancer (HDPC) did not show any statistically significant difference. In contrast, statistically significant difference was reported in moderate/intense GOLPH3 expression in cases diagnosed with HDPC and castration resistant prostate cancer (CRPC) (P < 0.0005). Moderate /intense expression of GOLPH3 was associated with androgen independence (P = 0.012), higher Gleason score (P = 0.017), bone metastasis (P = 0.024), higher baseline prostate-specific antigen (PSA) (P = 0.038), and higher PSA nadir (P = 0.032). A significantly negative correlation was found between moderate/intense GOLPH3 expression and disease-free survival (DFS) (HR = 0.28, P = 0.012) and overall survival (OS) (HR = 0.42, P = 0.027). Univariated analysis indicated that moderate/intense GOLPH3 expression created a significantly prognostic impact in patients with CRPC. On the other hand, multivariate analysis indicated that GOLPH3 was a significantly independent prognostic factor of DFS (P = 0.027) in all prostate cancer patients.ConclusionsIn this study, it was discovered that the overexpression of GOLPH3 is associated with the transition of prostate cancer from hormone sensitive phase to hormone refractory phase. GOLPH3 might be an important prognostic factor of DFS and OS in patients with prostate cancer. In totality, GOLPH3 could be used as a novel candidate in devising a more effective therapeutic strategy to tackle CRPC.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1452541171722856.

943P - Openact: Phase 2, Open-Label Study of Sipuleucel-T in Metastatic Castrate-Resistant Prostate Cancer (MCRPC)

ABSTRACT Background Sipuleucel-T is an FDA-approved autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic mCRPC. In the Phase 3 IMPACT trial, sipuleucel-T showed a 22% reduction in risk of death (p = 0.032) and a 4.1-month median OS improvement (25.8 vs 21.7 months) compared with control. OpenACT (P09-1; NCT00901342) is a Phase 2 open-label study to further evaluate the safety and immune responses of sipuleucel-T in patients (pts) with mCRPC. Methods Pts received sipuleucel-T at 2-week (wk) intervals for a total of 3 infusions. Sipuleucel-T is manufactured from autologous PBMCs isolated by leukapheresis at wks 0, 2 and 4, and activated with PA2024 (a recombinant fusion protein composed of prostatic acid phosphatase [PAP] linked to GM-CSF). Cell activation is measured by upregulation of the costimulatory molecule CD54. The primary endpoint was to evaluate the magnitude of immune responses to sipuleucel-T treatment. Results From October 2009–June 2010, 104 pts were enrolled; 101 pts received ≥1 leukapheresis and 98 pts received ≥1 infusion (safety population). Pts who had received prior docetaxel (D; 29.3% of enrolled pts) had a higher baseline prostate-specific antigen (90 vs 40ng/mL) and a greater proportion with a time from diagnosis of ≥6 years (93.5% vs 68.7%) compared with pts with no prior D exposure. Consistent with previous studies, CD54 upregulation and post-culture cytokine levels were significantly greater at wk2 and wk4 compared with wk0 (p Discussion Sipuleucel-T generates antigen-specific immune responses in patients with and without prior D exposure. However, product characteristics suggest that patients without prior D may generate sip-T products with higher TNC, which has previously been shown to correlate with prolonged survival, supporting earlier use in the mCRPC treatment paradigm. Disclosure J. Corman: On the Board of Directors for Benaroya Research Institute and employee of Virginia Mason Medical Center, N. Dawson: Corporate sponsored research for Dendreon Corporation, and participation in Speakers Bureau also for Dendreon Corporation, S. Hall: Corporate sponsored research for Dendreon and Medivation, C. Nabhan: Participation in corporate sponsored research and speakers bureau, A. Ferrari: Participation in advisory boards, A.J. Armstrong: Advisory boards for Bristol Myers Squibb, Bayer, Amgen; sponsored research for Dendreon, Sanofi Aventis, Medivation, Eli Lilly, Pfizer, Novartis, Janssen Biotech, Kanglaite Active Biotech/Ipsen; speaker for Dendreon, Sanofi Aventis, Amgen, Pfizer, F. Stewart: Employee and stock ownership in Dendreon Corporation, N. Sheikh: Employee of and stock ownership in Dendreon Corporation, D.P. Petrylak: Advisory boards for Amgen, Bayer, Pfizer, Ferring, Millenium, Novartis, Dendreon, Johnson and Johnson, GlaxoSmithKline; sponsored research Celgene, Dendreon, Sanofi, Pfizer, AstraZeneca, GlaxoSmithKline, Rogesen Institute, Boheringer Ingelheim, All other authors have declared no conflicts of interest.

Dried Plums = Fiber for Chronic Constipation

Several studies suggest that a baseline prostate specific antigen (PSA) measured in young men predicts future risk of prostate cancer. Considering recent recommendations against PSA screening, high-risk populations (e.g. black men, men with a high baseline PSA) may be particularly vulnerable in the coming years. Thus, we investigated the relationship between baseline PSA and future prostate cancer in a black majority–minority urban population.A retrospective analysis was performed of the prostate biopsy database (n = 994) at the Brooklyn Veterans Affairs Hospital. These men were referred to urology clinic for elevated PSA and biopsied between 2007 and 2014. Multivariate logistic regression was used to predict positive prostate biopsy from log-transformed baseline PSA, race (black, white, or other), and several other variables.The majority of men identified as black (50.2%). Median age at time of baseline PSA and biopsy was 58.6 and 64.8, respectively. Median baseline PSA was similar among black men and white men (2.70 vs 2.91 for black men vs white men, p = 0.232). Even so, black men were more likely than white men to be diagnosed with prostate cancer (OR 1.62, p < 0.0001). Black men less than age 70 were at particularly greater risk than their white counterparts. Baseline PSA was not a statistically significant predictor of future prostate cancer (p = 0.101).Black men were more likely to be diagnosed with prostate cancer than were white men, despite comparable baseline PSA. In our pre-screened population at the urology clinic, a retrospective examination of baseline PSA did not predict future prostate cancer.

Long-Term Hormonal Therapy: Who Would Benefit?

Traditionally, the role of hormonal therapy (HT) for prostate cancer (PCa) has been the palliative treatment of advanced and metastatic disease. Recently, advances in the development of androgen-deprivation therapy (ADT) with luteinising hormone-releasing hormone (LHRH) agonists have made LHRH agonists the standard of care for 90% of men with advanced or metastatic PCa. Although the role of ADT is historically well defined, recent studies demonstrate that the treatment of advanced or metastatic PCa with ADT can be tailored to the needs of the patient. This may be achieved by the immediate or deferred initiation of ADT (orchiectomy or LHRH agonist treatment) depending upon the nature of the disease and the patient's age. Patients who are likely to die of non-PCa-related causes prior to an indication for treatment initiation, for example, may benefit from deferred treatment, which may spare them the burden of treatment-related adverse events. In contrast, patients who are likely to die of PCa-related causes may benefit from immediate treatment because this option may delay disease progression and reduce symptom burden. Additionally, recent studies have shown that prognostic disease markers such as prostate-specific antigen (PSA) and PSA doubling time (PSA DT) can be used as indicators of who may receive the greatest benefit from treatment. Patients with a high baseline PSA level or a short PSA DT (markers of aggressive and/or advanced disease), for example, are more likely to die of disease-related causes than patients with low baseline PSA levels or long PSA DT. Furthermore, recent studies have shown that HT may be used successfully in adjuvant settings for patients in earlier stages of the disease and/or who require radical treatment. This paper reviews which patients can benefit from HT in terms of treatment timing, baseline prognostic indicators, disease stage, and adjuvant use.

Prognostic Factors Affecting Progression and Survival in Metastatic Prostate Cancer

Purpose: To evaluate the role of age, Gleason score, prostate-specific antigen (PSA), PSA doubling time (PSADT), and PSA half-time (PSAT_1/2) as prognostic factors in metastatic prostate cancer to predict long-term outcome. Patients and Methods: 412 patients with metastatic prostate cancer diagnosed after January 1995, with at least 6 months of follow-up, were enrolled. Serum PSA was determined at diagnosis and every 3–6 months thereafter. All patients underwent medical or surgical castration. End points of the study were either death or disease progression. Univariate and multivariate Cox proportional hazard analysis was used to evaluate prognostic factors. Results: Median progression-free and overall survival was 3 and 5.7 years. Patients aged ≤65 years at diagnosis, high baseline PSA and high nadir PSA were associated with poor overall survival. Patients with a PSAT_1/2 of <6 months, high baseline alkaline phosphatase, and PSADT of <1 month had significantly poorer progression-free and overall survival. Conclusion: Prostate cancer is a common malignancy in the elderly population. We have found that younger patients with high baseline and nadir PSA, shorter PSADT and PSAT_1/2 have poorer overall and progression-free survival.

Additional Analysis of the Secondary End Point of Biochemical Recurrence Rate in a Phase 3 Trial (CS21) Comparing Degarelix 80 mg Versus Leuprolide in Prostate Cancer Patients Segmented by Baseline Characteristics

BackgroundRecent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients. ObjectiveTo compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival. Design, setting, and participantsPhase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240mg for 1 mo, and then 80mg monthly (240/80mg); degarelix at 240mg for 1 mo, and then 160mg monthly; and leuprolide at 7.5mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer). MeasurementsPSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and ≥5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (<10, 10–20, >20–50, and >50 ng/ml) were analysed. Results and limitationsPatients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p=0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p=0.04). The relatively low number of patients in each subgroup is a limitation of this study. ConclusionsThese results generate the hypothesis that degarelix at 240/80mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings.

The influence of unscheduled biopsies on prostate cancer detection in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial

1504^ Background: REDUCE is an ongoing 4-year, international, randomized, placebo-controlled study investigating the effect of dutasteride on the incidence of biopsy-detectable prostate cancer (PCa). We assessed the influence of prostate specific antigen (PSA)-driven, unscheduled biopsies on PCa detection. Methods: Eligible subjects were aged 50–75 years with serum PSA 2.5–10 ng/mL (50–60 years) or 3–10 ng/mL (&gt;60 years) and a negative 6–12-core biopsy ≤6 months before enrollment. Protocol-mandated transrectal ultrasound directed biopsies (10 cores) were taken at 2 and 4 years; we report unblinded 2-year data. Results: Of the 8108 subjects in the efficacy population (subjects with no PCa in baseline biopsy as assessed by Central lab and who took at least one dose of study medication), 356 subjects (4.4%) underwent an unscheduled biopsy (0–18 months), and 6460 subjects (79.7%) underwent a protocol-mandated (scheduled) biopsy (19–24 months). Rising PSA was the primary reason for an unscheduled biopsy. PCa was diagnosed in 60 subjects (16.9%) at an unscheduled biopsy compared with 950 subjects (14.7%) at scheduled biopsy. Subjects with PCa on unscheduled, compared with scheduled, biopsy had higher baseline PSA (6.63 vs. 6.06 ng/mL), lower % free PSA (13.2% vs. 15.5%); there was no difference in the mean number of baseline biopsy cores (8.6 vs. 8.4). Conclusions: Although unscheduled biopsies in REDUCE were slightly more likely to result in a cancer diagnosis and have a higher Gleason score, the small number of such biopsies (356/6591, 5.4% of subjects biopsied) would not cause a significant ascertainment bias. This contrasts the prostate cancer prevention trial (PCPT), where close to 40% of subjects had for-cause biopsies (most often PSA-driven), creating a substantial detection bias for high-grade cancers. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .