Primary Androgen Deprivation Therapy Research Articles

Psoas mass index at the level of the third lumbar vertebra on computed tomography is a prognostic predictor for metastatic castration-sensitive prostate cancer.

Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters. We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm2]/height2 [m2]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes. The median follow-up was 56.9months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm2/m2). Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer.

The effect of human leukocyte antigen genotype on survival in advanced prostate cancer treated with primary androgen deprivation therapy: the KYUCOG-1401-A study.

Immune editing, in which human leukocyte antigens (HLA) have critical roles, has been suggested to shape the landscape of human cancer. This study prospectively investigated whether HLA gene zygosity is associated with the prognosis of primary androgen deprivation therapy in advanced prostate cancer. KYUCOG-1401-A was conducted in conjunction with a prospective clinical trial (KYUCOG-1401). Among the patients enrolled in KYUCOG-1401 and treated with primary androgen deprivation therapy, only Japanese patients were included. HLA genotypes of HLA-A, B, C, DRB1, DQB1, and DPB1 were determined. The effect of divergence of HLA genotypes on time to progression, prostate cancer-specific survival, and overall survival was evaluated. Among 127 patients, homozygosity for HLA-DRB1 (HR, 95% CI; 4.05, 1.54-10.7, P = 0.0047) and HLA-DQB1 (HR, 95% CI; 3.75, 1.47-9.58, P = 0.0058) was associated with an increased risk of prostate cancer-specific mortality. Patients with higher HLA evolutionary divergence scores at HLA-DQB1 (HR, 95% CI; 0.90, 0.82-0.97, P = 0.0093) had lower risks of prostate cancer-specific mortality. Androgen-responsive gene sets were upregulated in CD4low and CD8low tumors in the prostate cancer cohort, but not in the bladder and kidney cancer cohorts. This study suggested that the diversity of HLA-II loci including HLA-DRB1 and HLA-DQB1 plays an important role in advanced prostate cancer survival, contributing to improved risk stratification in advanced prostate cancer. Moreover, it was shown that CD4+ T cells play an important role in androgen deprivation therapy, suggesting that immunotherapy targeting CD4+ T cells is promising for prostate cancer.

Role of Bone Scan Index (BSI) in the Prognosis and Treatment Efficacy in Castration-Sensitive Prostate Cancer Patients with Bone Metastasis

Bone is the most common metastatic site in prostate cancer (PCa). Although the extent of disease (EOD) grade is used for evaluating burden of bone metastasis, the accuracy of bone metastasis classification needs improvement. Bone scan index (BSI) was developed as a quantitative tool to enhance the interpretability and clinical relevance of the bone scan. This study aimed to explore the role of BSI using BONENAVI® software in determining the prognosis and treatment efficacy in castration-sensitive PCa (mCSPC) patients with bone metastasis. We retrospectively reviewed 61 mCSPC patients with bone metastasis who had received primary androgen deprivation therapy (PADT) at our institution. All patients received PADT with luteinizing hormone-releasing hormone agonist or surgical castration accompanied by first-generation antiandrogen, bicalutamide. Bone scans were performed with ⁹⁹[m]Tc-MDP. BSI (%) was divided into two groups (＜1.0 and ≧1.0), and BSI response rates(change at 0 months to after 6 months) were determined using thresholds of 45% decline. Castration-resistant prostate cancer (CRPC) -free survival (CRPC-FS) and Overall survival (OS) rates were analyzed using the Kaplan-Meier method. The median follow-up was 41. 9 months. Overall, 16 patients (26. 2%) died. Multivariate analysis on pretreatment factors revealed that hemoglobin (P＝0.03) and BSI (P＝0.04) were independent prognostic factors for OS. The 5-year OS rates in patients with low BSI and high BSI were 84.6% and 39.2%, respectively (P＝0.02). In 40 patients who had a bone scan before and after PADT, OS rates in patients with a good response (≧45%) were significantly higher than those with a poor response (＜45%) (P＝0.001). Nadir PSA titers within 6 months after the start of treatment (P＝0.005), Hb (P＝0.003), and BSI change (P＝0.014) were independent prognostic factors for OS. In mCSPC patients with bone metastases, BSI at diagnosis was an important predictor of CRPC progression and OS as a pre-treatment factor, and BSI change rate and PSA nadir as post-treatment factors.

Carbon Ion Radiation Therapy for Nonmetastatic Castration-Resistant Prostate Cancer: A Retrospective Analysis

PurposeTreatment outcomes of definitive photon radiotherapy for nonmetastatic castration-resistant prostate cancer (nmCRPC) are reportedly unsatisfactory. Carbon ion radiotherapy (CIRT) has shown favorable tumor control in various malignancies, including radioresistant tumors. Therefore, we retrospectively evaluated the clinical outcomes of CIRT for nmCRPC. Methods and MaterialsPatients with nmCRPC (N0M0) treated with CIRT at a total dose of 57.6 Gy (relative biological effectiveness; RBE) in 16 fractions or 51.6 Gy (RBE) in 12 fractions were included. The castration-resistant status was diagnosed based on prostate-specific antigen kinetics showing a monotonic increase during primary androgen deprivation therapy (ADT) or the need to change ADT. Clinical factors associated with patient prognosis were explored. Twenty-three consecutive patients were identified from our database. The median follow-up period was 63.6 months (range, 14.1–120). ResultsSeven patients developed biochemical relapse, six had clinical relapse, and four died from the disease. The 5-year overall survival, local control rate, biochemical relapse-free survival, and clinical relapse-free survival were 87.5%, 95.7%, 70.3%, and 75.7%, respectively. One patient with diabetes mellitus requiring insulin injections and taking antiplatelet and anticoagulant drugs developed grade 3 hematuria and bladder tamponade after CIRT. None of the patients developed grade 4 or worse toxicity. ConclusionsThe present findings indicate the acceptable safety and favorable efficacy of CIRT, encouraging further research on CIRT for nmCRPC.

A US real-world study of treatment patterns and outcomes in localized or locally advanced prostate cancer patients

PurposeMen with localized or locally advanced prostate cancer (LPC/LAPC) are at risk of progression after radiotherapy (RT) or radical prostatectomy (RP). Using real-world data, we evaluated patient characteristics, treatment patterns, and outcomes in LPC/LAPC.MethodsOptum claims and electronic health records (EHR) data from January 2010 to December 2021 were queried for men with LPC/LAPC who received primary RT, RP, or androgen deprivation therapy alone within 180 days after diagnosis. Survival outcomes were analyzed using descriptive statistics and Kaplan–Meier curves. Real-world overall survival (rwOS) was compared in patients with and without evidence of disease (i.e., disease recurrence, metastasis, diagnosis of castration-resistant PC) at defined time points.Results61,772 and 62,361 men in claims and EHR cohorts met the inclusion criteria. Median follow-up was 719 and 901 days, respectively. Most men received primary RT (51.0% claims, 35.0% EHR) or RP (39.4% claims, 53.8% EHR). Survival was greatest among men treated with RP, followed by RT. Adjusted for age and comorbidity, rwOS was shorter among men with evidence of disease within 1, 3, 4, and 5 years after primary treatment than those without at the same time points.ConclusionReal-world claims and EHR data show that survival among men with LPC/LAPC differs by primary treatment and time point of disease recurrence thereafter. Poor outcomes in men with LPC/LAPC who progress early indicate an unmet medical need for more effective primary treatment. If validated for surrogacy, no evidence of disease at specific time points could represent an intermediate efficacy endpoint in future trials.

Central Nervous System-related Conditions and Associated Healthcare Resource Use Among Japanese nmCRPC Patients Based on Retrospective Claims Data.

Background: Japanese patients with prostate cancer are typically treated with primary androgen deprivation therapy (ADT), most commonly administered as a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and an antiandrogen (AA). Since LHRH agonists and AA therapy can be maintained for several years, the long-term effects of these treatments on patients must be carefully considered, including the risk of concomitant central nervous system (CNS) conditions which could affect treatment choices. Objective: To describe CNS-related concomitant conditions during ADT and/or AA treatment and the subsequent healthcare resource utilization in Japanese nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. Methods: Patients diagnosed with nmCRPC and CNS-related conditions while on ADT and/or AA therapy between April 2009 and August 2017 were retrospectively followed up for a maximum of 2 years using a claims database. Results: A total of 455 patients (average age, 78.5 years), were included. The 3 most common concomitant CNS-related conditions were pain (~60% of events), insomnia (~30%), and headache (2%-3%). The frequency of CNS-related conditions in these patients increased approximately threefold after starting AA therapy (before, 969 events; after, 2802). On average, a patient had 10 episodes of concomitant CNS-related conditions in a year. Medical costs did not significantly increase due to CNS-related conditions. Discussion: The most frequently reported CNS-related conditions were pain, insomnia, and headaches. Furthermore, more concomitant CNS-related conditions 1 year after CRPC diagnosis and 1 year after starting AA treatment were recorded. Conclusion: Patients with nmCRPC experience an increase in the frequency of concomitant CNS-related conditions, including pain, insomnia, and headaches, after CRPC diagnosis or starting AA treatment. Future research should explore the causes of this increased frequency.

Central Nervous System-related Conditions and Associated Healthcare Resource Use Among Japanese nmCRPC Patients Based on Retrospective Claims Data

Background: Japanese patients with prostate cancer are typically treated with primary androgen deprivation therapy (ADT), most commonly administered as a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and an antiandrogen (AA). Since LHRH agonists and AA therapy can be maintained for several years, the long-term effects of these treatments on patients must be carefully considered, including the risk of concomitant central nervous system (CNS) conditions which could affect treatment choices. Objective: To describe CNS-related concomitant conditions during ADT and/or AA treatment and the subsequent healthcare resource utilization in Japanese nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. Methods: Patients diagnosed with nmCRPC and CNS-related conditions while on ADT and/or AA therapy between April 2009 and August 2017 were retrospectively followed up for a maximum of 2 years using a claims database. Results: A total of 455 patients (average age, 78.5 years), were included. The 3 most common concomitant CNS-related conditions were pain (~60% of events), insomnia (~30%), and headache (2%-3%). The frequency of CNS-related conditions in these patients increased approximately threefold after starting AA therapy (before, 969 events; after, 2802). On average, a patient had 10 episodes of concomitant CNS-related conditions in a year. Medical costs did not significantly increase due to CNS-related conditions. Discussion: The most frequently reported CNS-related conditions were pain, insomnia, and headaches. Furthermore, more concomitant CNS-related conditions 1 year after CRPC diagnosis and 1 year after starting AA treatment were recorded. Conclusion: Patients with nmCRPC experience an increase in the frequency of concomitant CNS-related conditions, including pain, insomnia, and headaches, after CRPC diagnosis or starting AA treatment. Future research should explore the causes of this increased frequency.

Long-term Prostate Cancer–specific Mortality After Prostatectomy, Brachytherapy, External Beam Radiation Therapy, Hormonal Therapy, or Monitoring for Localized Prostate Cancer

BackgroundThe optimal treatment of localized prostate cancer (PCa) remains controversial. ObjectiveTo compare long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (active surveillance [AS]/watchful waiting [WW]) for PCa. Design, setting, and participantsThis is a cohort study with long-term follow-up from the multicenter, prospective, largely community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Men with biopsy-proven, clinical T1–3aN0M0, localized PCa were consecutively accrued within 6 mo of diagnosis and had clinical risk data and at least 12 mo of follow-up after diagnosis available. Outcome measurements and statistical analysisPCa risk was assessed, and multivariable analyses were performed to compare PCa-specific mortality (PCSM) and all-cause mortality by primary treatment, with extensive adjustment for age and case mix using the Cancer of the Prostate Risk Assessment (CAPRA) score and a well-validated nomogram. Results and limitationsAmong 11 864 men, 6227 (53%) underwent RP, 1645 (14%) received BT, 1462 (12%) received EBRT, 1510 (13%) received PADT, and 1020 (9%) were managed with AS/WW. At a median of 9.4 yr (interquartile range 5.8–13.7) after treatment, 764 men had died from PCa. After adjusting for CAPRA score, the hazard ratios for PCSM with RP as the reference were 1.57 (95% confidence interval [CI] 1.24–1.98; p < 0.001) for BT, 1.55 (95% CI 1.26–1.91; p < 0.001) for EBRT, 2.36 (95% CI 1.94–2.87; p < 0.001) for PADT, and 1.76 (95% CI 1.30–2.40; p < 0.001) for AS/WW. In models for long-term outcomes, PCSM differences were negligible for low-risk disease and increased progressively with risk. Limitations include the evolution of diagnostic and therapeutic strategies for PCa over time. In this nonrandomized study, the possibility of residual confounding remains salient. ConclusionsIn a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, PCSM was lower after local therapy for those with higher-risk disease, and in particular after RP. Confirmation of these results via long-term follow-up of ongoing trials is awaited. Patient summaryWe evaluated different treatment options for localized prostate cancer in a large group of patients who were treated mostly in nonacademic medical centers. Results from nonrandomized trials should be interpret with caution, but even after careful risk adjustment, survival rates for men with higher-risk cancer appeared to be highest for patients whose first treatment was surgery rather than radiotherapy, hormones, or monitoring.

A multicenter, retrospective observational study investigating baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer treated with primary androgen deprivation therapy.

This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. Of the 2494 patients (goserelin, n=564; leuprorelin, n=1148; surgical castration, n=161; degarelix, n=621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7months for surgical castration and 54.0months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n=195). This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.

Pretreatment Lymphocyte to C-Reactive Protein Ratio: An Independent Predictor of Overall Survival in Metastatic Hormone-Naïve Prostate Cancer Patients

IntroductionThe purpose of this study was to investigate the clinical value of combination of systematic inflammatory factors in predicting the outcomes of primary androgen deprivation therapy (ADT) plus first-generation antiandrogen treatment in metastatic hormone-naïve prostate cancer (mHNPC) patients. Materials and MethodsA total of 361 consecutive mHNPC patients from the discovery (n = 165) and validation (n = 196) cohorts were analyzed. All patients received primary ADT with surgical castration or pharmacologic castration accompanied by first-generation antiandrogens. We evaluated the prognostic impact of pretreatment lymphocyte to C-reactive protein ratio (LCR) on overall survival (OS) in both cohorts. ResultsThe median follow-up in the discovery and validation cohorts was 43.4 and 50.9 months, respectively. In the discovery cohort, low LCR (using an optimal cutoff threshold of 14,025) was significantly correlated with poor OS compared with high LCR (P < .001). Multivariate analysis revealed that the biopsy Gleason score and LCR were independent prognostic factors for OS. In the validation cohort, low LCR was also significantly correlated with poor OS compared with high LCR (P = .001). A multivariate analysis revealed that the extent of disease on bone scan grade, lactate dehydrogenase, and LCR were all independent predictors of OS. ConclusionsPretreatment low LCR is an independent predictor of poor OS in mHNPC patients. This may be informative in predicting the susceptible patients’ developing worse outcomes after being treated with primary ADT plus first-generation antiandrogen.

Genome-wide association studies in advanced prostate cancer: KYUCOG-1401-A study.

Androgen deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (PFS) at 1 year and adverse events including de novo diabetes mellitus, arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with radiographic PFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and overall survival in ADT. In addition, GWAS showed that several SNPs were associated with de novo diabetes mellitus, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.

MP54-03 THE EFFECT OF DUAL ELIGIBILITY ON ACCESS TO CARE IN PATIENTS WITH NEWLY DIAGNOSED PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP54-03 THE EFFECT OF DUAL ELIGIBILITY ON ACCESS TO CARE IN PATIENTS WITH NEWLY DIAGNOSED PROSTATE CANCER Kassem Faraj, Rodney Dunn, Brent Hollenbeck, and Lindsey Herrel Kassem FarajKassem Faraj More articles by this author , Rodney DunnRodney Dunn More articles by this author , Brent HollenbeckBrent Hollenbeck More articles by this author , and Lindsey HerrelLindsey Herrel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003307.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Dual eligible beneficiaries are a particularly vulnerable population, as they qualify for Medicare due to age and Medicaid due to low income. Though some dual eligible beneficiaries have access to additional social services, such as transportation coverage, others do not qualify for these services (i.e. partial dual eligibility). This heterogeneity in support services may impact access to treatment for dual eligible men with newly diagnosed prostate cancer, a condition that necessitates timely, repeated interactions with the healthcare system. METHODS: We performed a cohort study of Medicare beneficiaries who were diagnosed with prostate cancer between 2015 and 2019. Beneficiaries were required to have 12-months of eligibility before and after diagnosis date. We compared pre-diagnosis testing, post-diagnosis testing, and primary prostate cancer treatment between beneficiaries who have full dual-eligibility (full duals, “F”), partial dual-eligibility (partial duals, “P”) and those who are not dual-eligible (non-duals, “N”). RESULTS: In 138,785 men with newly diagnosed prostate cancer, 4,611 (3.3%) were full duals and 2,031 (1.5%) were partial duals. Full and partial duals (Figure 1) were more often of Black race than non-duals (p<0.001). Partial duals were less likely to have a PSA (p<0.001) or multiparametric MRI (p<0.001) prior to diagnosis, compared to both duals and non-duals. After diagnosis, full and partial duals less commonly underwent multiparametric MRI (F-17%, P-15%, N-24%, p<0.001) and more commonly underwent bone scan (F-43%, P-42%, N-33%, p<0.001) compared to non-duals. Regarding treatment (Figure 1), full and partial duals less commonly underwent surgery (F-12%, P-13%, N-20%) and more commonly received androgen deprivation therapy as a primary treatment (F-16%, P-13%, N-7%) compared to non-duals (p<0.001). CONCLUSIONS: Our findings demonstrate disparities in access for dual-eligible beneficiaries before and after a new prostate cancer diagnosis. A more advanced stage at diagnosis may be reflected by the higher rates of bone scan testing and treatment with primary androgen deprivation therapy in the duals. A deeper understanding of barriers in access to prostate cancer screening and treatment is needed for this particularly vulnerable population. Source of Funding: This study is supported by funding from the National Cancer Institute Advanced Training in Urologic Oncology T32 Grant No T32CA180984 (Faraj) and by funding from the Prostate Cancer Foundation-Pfizer Health Equity Grant No K08CA237638 (Herrel) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e754 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kassem Faraj More articles by this author Rodney Dunn More articles by this author Brent Hollenbeck More articles by this author Lindsey Herrel More articles by this author Expand All Advertisement PDF downloadLoading ...

MP21-20 SOCIAL VULNERABILITY AND TREATMENT PATTERNS IN PATIENTS WITH PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP21-20 SOCIAL VULNERABILITY AND TREATMENT PATTERNS IN PATIENTS WITH PROSTATE CANCER Rishi Sekar, Kassem Faraj, Rodney L. Dunn, and Lindsey Herrel Rishi SekarRishi Sekar More articles by this author , Kassem FarajKassem Faraj More articles by this author , Rodney L. DunnRodney L. Dunn More articles by this author , and Lindsey HerrelLindsey Herrel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003246.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Individual characteristics such as race, ethnicity, and socioeconomic status (SES) are well-established risk factors for poor outcomes across the care continuum in various cancers, including prostate cancer. However, these metrics may not capture the complexity of social determinants of health (SDOH) and systemic barriers that often underlie suboptimal care. We evaluate the association of community-level SDOH as measured by the Centers for Disease Control and Prevention’s Social Vulnerability Index (SVI) with diagnostic and treatment patterns in patients with newly diagnosed prostate cancer (PCa). METHODS: We used Medicare claims data to perform a retrospective cohort study of men >65 years with newly diagnosed PCa between 2015-2019. SVI was abstracted and linked to each beneficiary at the county-level and categorized into quartiles (i.e., least vulnerable to most vulnerable). Patient demographics, SES measures, diagnostic and treatment modalities were compared across SVI quartiles. Group comparisons were tested with chi-squared analyses. RESULTS: We identified 138,207 men with newly diagnosed PCa. A greater proportion of men residing in the most vulnerable counties were older, of minority status, more comorbid, living in rural locations with lower SES, and more often dual-eligible (all p<0.001). In terms of diagnosis, these men were less likely to undergo prostate MRI prior to or after diagnosis, but more likely to have a bone scan after diagnosis (all p<0.001). In terms of treatment, these men were less likely to be managed with active treatment (prostatectomy or radiation therapy), and more likely to be managed with primary ADT or active surveillance (all p<0.001). CONCLUSIONS: In a large cohort of Medicare beneficiaries with newly diagnosed PCa, men residing in higher SVI counties were more disadvantaged, less likely to undergo appropriate diagnostic testing, and less likely to be managed with definitive local therapy. Measuring, understanding, and mitigating SDOH is necessary to provide equitable cancer care for patients with PCa. Source of Funding: Prostate Cancer Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e294 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rishi Sekar More articles by this author Kassem Faraj More articles by this author Rodney L. Dunn More articles by this author Lindsey Herrel More articles by this author Expand All Advertisement PDF downloadLoading ...

Randomized, double-blinded phase II study of ketoconazole (keto), hydrocortisone (HC), and anti-PSMA antibody J591 labeled with 177Lu or 111In in patients (pts) with high-risk non-metastatic (met) castration-resistant prostate cancer (M0 CRPC).

LBA21 Background: Up to 1/3 of pts develop biochemical relapse following primary therapy. Many are not cured with salvage local therapy, likely because of undetectable distant disease. PSMA is expressed on most PC and can be targeted by radiolabeled J591. 177Lu is a predominantly β-emitting radionuclide and also has γ emission which allows imaging. 111In is predominantly a γ emitter, also with some auger emission for therapy. Hormonal therapy is effective and may increase PSMA expression and radiosensitize. In this DOD-funded study initiated in the pre-PSMA PET and AR signaling inhibitor era, we hypothesized that 177Lu prolongs 18-month (mo) met-free survival (MFS) more than 111In in pts with high risk, M0 CRPC when targeting PSMA via J591 in combo with keto and HC. Methods: Pts with high-risk M0 CRPC defined by PSA DT &lt; 8 mo and/or absolute PSA &gt; 20 ng/mL and serum testosterone &lt; 50 ng/mL with no evidence of metastatic disease on CT/MRI and bone scan were eligible. Treatment included a minimum 4 week lead-in with keto 400 mg TID and HC 20 mg AM, 10 mg PM (both of which could be continued until unacceptable toxicity or development of mets) and a single infusion of J591 with 2:1 randomization to 177Lu (70 mCi/m2) or 111In (5 mCi) in double-blinded fashion. The final version of the protocol was designed to randomize 55 pts for 80% power to detect a difference in 18-mo MFS with one-sided alpha of 10%. Secondary endpoints include median MFS, PSA response, overall survival, and toxicity. Results: 55 pts with median age 68 (range 52 - 88), 75% prostatectomy, 23% primary radiation, 2% primary ADT; 19% local salvage therapy. Median PSA doubling time 3 mo (range 0.87 – 7.85), median baseline PSA 8.0 (range 1-78). In intent to treat analysis (5 without imaging and 4 lost to follow up by 18 mo), 50% developed mets by 18 mo with 177Lu vs 76% with 111In (p=0.066). Median MFS was 23.8 mo vs 20.8 mo, and biochemical PFS was 18.67 vs 8.87 mo, favoring 177Lu in analyses censoring start of new treatment. Confirmed &gt;50% PSA decline occurred in 82% with 177Lu and 71% with 111In. Grade &gt;3 heme AEs were more common with 177Lu vs 111In, including neutropenia (57% vs 11%, with 1 febrile neutropenia) and thrombocytopenia (77% vs 11%, with 25% vs 6% platelet transfusions), whereas Gr &gt;3 non-heme AEs were less common with 177Lu vs 111In, including abdominal pain (0 vs 11%), ALT increase (3.3% vs 22%), and diarrhea (0 vs 22%). Conclusions: Anti-PSMA mAb J591 with keto/HC when radiolabeled with 177Lu leads to improved 18-month met-free survival vs 111In. Most pts had significant PSA decline with either version of radiolabeled J591 with keto/HC. Hematologic toxicity is more common with 177Lu. This supports the development of anti-PSMA radioimmunotherapy for low volume advanced PC, though the optimal radionuclide and targeting agent is unknown. Clinical trial information: NCT00859781 .

Validity and Future of Primary Androgen Deprivation Therapy in Prostate Cancer. Integration in the Era of New Agents Targeting the Androgen Receptor.

The relationship of sex hormones with prostate glandular activity and the evidence of the favourable impact of bilateral orchiectomy in 21 patients with locally advanced or metastatic prostate cancer (PCa), ratified by Huggins C.B. and cols. in 1941, is one of the pillars for the acceptance of androgen deprivation therapy (ADT). Its clinical relevance has withstood the passage of time and remains valid, fundamentally, in advanced PCa. ADT has expanded its use over the years and, after extensive clinical experience, substantial modifications have been incorporated into its indications and options, both of which are increasingly precise. The objective of this review is to update the therapeutic positioning of primary ADT, genetic-molecular advances and future of the developing treatments of PCa.

Prostate-specific Antigen Kinetics During Androgen-deprivation Therapy Predict Response to Enzalutamide in Metastatic Castration-resistant Prostate Cancer.

No practical predictive biomarkers exist to date for the response to androgen receptor-axis targeted (ARAT) therapies in metastatic castration-resistant prostate cancer (mCRPC). This study investigated whether prostate-specific antigen (PSA) kinetics in primary androgen-deprivation therapy for advanced hormone-sensitive prostate cancer may be associated with the response to ARAT agents in mCRPC. This study assessed 102 patients with mCRPC treated with enzalutamide or abiraterone to evaluate the associations between clinical outcomes and PSA kinetics, including the ratio of initial to nadir PSA (I/N PSA) level in primary combined androgen blockade. The PSA response was defined as a ≥50% decrease at 3 months from baseline in patients with mCRPC. In patients treated with enzalutamide, the optimal cut-off I/N PSA value for PSA response was 531 ng/ml (sensitivity=66.7%, specificity=88.2%, area under the curve=0.73, using a receiver operating characteristic curve). The PSA response was 83.3% and 25.0% in the high and low I/N PSA groups, respectively. The median overall survival and radiographic progression-free survival from enzalutamide initiation were longer for the high compared to the low I/N PSA group. Multivariate analysis revealed I/N PSA (hazard ratio=0.275, p=0.026) as an independent risk factor for overall survival in the patients treated with enzalutamide. In contrast, I/N PSA showed no predictive ability for PSA response in patients treated with abiraterone. In patients with mCRPC, I/N PSA can be a practical predictive biomarker for response to the ARAT agent enzalutamide.

Clinicopathological and immunological profiles of prostate adenocarcinoma and neuroendocrine prostate cancer

BackgroundBiomarkers of DNA damage repair deficiency provide opportunities for personalized treatment with immunotherapy. However, there is limited research on the immune microenvironment of adeno-neuroendocrine prostate cancer (NEPC). In this study, we aimed to assess and describe the comprehensive clinicopathological manifestations of NEPC to improve diagnosis and predict prognosis.MethodsA retrospective medical record review of 66 patients with prostate cancer (PCa) was performed. PCa samples from the 66 patients were analyzed using immunohistochemical staining for the detection of chromogranin, neural cell adhesion molecule 1, and synaptophysin. For tumor-associated immune microenvironment analysis, PD-L1, CD3, and CD8 were labeled in tissue slides. The effect of clinicopathological factors on the survival of patients with Adeno-NEPC was analyzed.ResultsTwenty patients presented with adeno-NEPC, whereas 46 presented with adeno-PCa. The median age of patients at PCa diagnosis was 67.86 ± 7.05 years (68.65 ± 7.23 years, adeno-NEPC; 67.52 ± 7.02 years, adeno-PCa). Eleven patients with adeno-NEPC underwent prostatectomy, whereas nine received primary androgen deprivation therapy (ADT). Additionally, 30 patients with adeno-PCa underwent prostatectomy, whereas 16 (34.8%) received primary ADT. There was a significant difference in overall survival between patients with adeno-NEPC and those with adeno-PCa (46.0 months vs. 65.0 months). There was also a significant difference in time from prostatectomy to biochemical recurrence between the groups of patients who underwent prostatectomy. Prostatectomy and normal lactate dehydrogenase levels were clinical factors that were significantly associated with better outcomes in patients with adeno-NEPC. Metastatic adeno-NEPC was associated with a higher programmed death ligand 1 (PD-L1) score (2–4) than localized PCa. The data showed that PD-L1 expression in adeno-NEPC may be negatively associated with that in CD8+ T cells.ConclusionsOur study revealed clinicopathological manifestations of adeno-NEPC and some possible predictive factors significantly associated with better outcomes in patients with adeno-NEPC. These findings might be beneficial in the development of diagnostic strategies and customized treatment plans.

Pre-Treatment Hemoglobin Concentration and Absolute Monocyte Count as Independent Prognostic Factors for Survival in Localized or Locally Advanced Prostate Cancer Patients Undergoing Radiotherapy.

The prognostic value of inflammatory indices, such as the absolute monocyte count (AMC), has been a subject of interest in recent prostate cancer (PCa) studies, while hemoglobin concentration (HGB) has been recognized as a survival factor in castration-resistant metastatic prostate cancer, but its value remains unclear in localized diseases. The aim of this study was to test the prognostic value of these two simple and inexpensive biomarkers for survival and was based on a cohort of 1016 patients treated with primary radiotherapy and androgen deprivation therapy for localized or locally advanced intermediate- or high-risk PCa. Complete survival data were available for all cases and were based on the National Cancer Registry, with a median observation time of 120 months (Interquartile Range (IQR) 80.9–144.7). Missing blood test data were supplemented using the Nearest Neighbor Imputation, and the Cox Proportional Hazards Regression model was used for analysis. The median age was 68.8 years (IQR 63.3–73.5). The five-year overall survival was 82.8%, and 508 patients were alive at the time of analysis. The median time between blood tests and the first day of radiotherapy was 6 days (IQR 0–19). HGB (p = 0.009) and AMC (p = 0.003) were independent prognostic factors for survival, along with age, Gleason Grade Group, clinical T stage and maximum prostate-specific antigen concentration. This study demonstrates that HGB and AMC can be useful biomarkers for overall survival in patients treated with radiotherapy for localized intermediate- or high-risk PCa.

Characteristics of Patients in SPCG-15—A Randomized Trial Comparing Radical Prostatectomy with Primary Radiotherapy plus Androgen Deprivation Therapy in Men with Locally Advanced Prostate Cancer

BackgroundThere is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. ObjectiveTo describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design, setting, and participantsThis study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. InterventionRadical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysisCause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitationsThe distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45–75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. ConclusionsWe have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summaryThis study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer.

Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer.

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all‐cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008‐18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all‐cause mortality, were explored using time‐varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow‐up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05‐1.21), myocardial infarction (1.18: 1.05‐1.32), stroke (1.21: 1.06‐1.38), heart failure (1.23: 1.13‐1.35) and all‐cause mortality (1.49: 1.39‐1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all‐cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all‐cause mortality within the context of treatment guidelines and benefits of ADT.