Clinical characteristics and outcomes of patients with prostate cancer and parenchymal brain metastases (PBM).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 187-187
Author(s):  
Richard Martin Bambury ◽  
Vaios Hatzoglou ◽  
Kristen Rebecca Curtis ◽  
Gita V Patel ◽  
Howard I. Scher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Brain Metastases ◽  
Clinical Characteristics ◽  
Specific Antigen ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Gleason Grade ◽  
Primary Malignancy ◽  
Resistant Disease ◽  
Castration Resistant

187 Background: Parenchymal brain metastases' (PBM's) are rare in prostate cancer (PCa), but the introduction of novel therapies that prolong life for metastatic disease has raised the possibility that the distribution of disease may be changing as patients live longer. In an effort to establish the clinical characteristics and outcomes of PBM as a comparator for future studies, we reviewed all cases at our institution over a 13 year period. Methods: Patients (pts) diagnosed with PBM at Memorial Sloan-Kettering Cancer Center between 2000 and 2010 were retrospectively identified by billing codes for prostate cancer, brain metastases, and no additional primary cancers. Additional cases since 2010 were manually collected prospectively. Direct extension of osseous skull metastases or leptomeningeal disease were not considered PBM. Demographic, clinical, and pathologic characteristics were recorded. Results: 5,474 pts with metastatic PCa and no other primary malignancy were identified of whom 21 had PBM. An additional four PBM cases were prospectively identified, for a total of 25 pts. Twenty two pts (88%) had prostate adenocarcinoma (adeno), of which 14 had Gleason 8 or more disease, 20 had castration resistant disease, and nine had prostate-specific antigen (PSA) less than 5ng/mL. The other three (12%) had atypical histologies (osteosarcoma, small cell carcinoma, and high grade neuroendocrine carcinoma). Median time from diagnosis of PCa to diagnosis of PBM was 3.7 years (range 0 to 19.8) and from discovery of metastatic PCa to PBM was 2.3 years (range 0 to 10). At the time of PBM diagnosis all pts had 1 or more additional site of disease - bone metastases in 20 (80%), lung in 13 (52%), liver in nine (36%). Treatments included whole brain RT in 10 (45%), surgery +/- RT in 8 (36%) and stereotactic RT in 2 (9%). Median overall survival from diagnosis of PBM was 4.3 months (0.7-18.1) in adeno pts compared with 0.7 months (0.7-1.0) in atypical histology pts. Only four pts (16%) survived 12 or more months. Conclusions: In this contemporary cohort, PBM cases were often associated with PCa of atypical histology, high Gleason grade, frequent visceral disease, and low PSA production. Survival was poor after diagnosis of PBM despite treatment. These data can be used as a comparator to track whether treatment with novel PCa therapies is altering the incidence and characteristics of CNS involvement.

Characterization of PSA at death in patients with metastatic castration-resistant prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 184-184
Author(s):  
Krishna Bikkasani ◽  
Qian Qin ◽  
Justin Lin ◽  
Matt D. Galsky ◽  
Bobby Chi-Hung Liaw ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Characteristics ◽  
Descriptive Analysis ◽  
Specific Antigen ◽  
Predictive Biomarker ◽  
Mount Sinai Hospital ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Castration Resistant ◽  
Mount Sinai

184 Background: Prostate Specific Antigen (PSA) is a valuable prognostic and predictive biomarker in prostate cancer (PC). Currently, the significance of PSA at death is undefined. In this single institution retrospective study, we aim to characterize the significance of PSA at death in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we stratified patients into the following cohorts based on their PSA at death: < 10, 10-100, 100-1000, and > 1000 ng/ml. We excluded data of patients who had less than 3 visits to the Mount Sinai Hospital. A descriptive analysis was performed to assess clinical characteristics of disease, treatment response, and outcomes. Results: We identified 1097 PC patients, and 101 were found to be deceased following a diagnosis of mCRPC. Cohorts of higher PSA level at death were associated with: a lower Gleason score at diagnosis, a longer time to castration resistance, higher burden of metastatic disease at death (non-visceral and visceral), and longer OS in patients with mCRPC (see table). Conclusions: In this study, PSA at death is associated with several important clinical characteristics and outcome, including overall survival. These differences may be attributed to their underlying biologic behavior. These results are hypothesis generating, and larger studies will be needed to further assess the significance of these findings. [Table: see text]

scholarly journals Comparison of metastatic castration-resistant prostate cancer in bone with other sites: clinical characteristics, molecular features and immune status

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11133
Author(s):  
Zhengquan Xu ◽  
Yanhong Ding ◽  
Wei Lu ◽  
Ke Zhang ◽  
Fei Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Characteristics ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Specific Antigen ◽  
Functional Enrichment ◽  
Castration Resistant Prostate Cancer ◽  
Hub Genes ◽  
Molecular Features ◽  
Castration Resistant

Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage and the leading cause of death in prostate cancer patients, among which bone metastasis is the most common site. Here in this article, we downloaded the gene expression data and clinical information from online dataset. We found that prostate cancer metastasis in bone is prone to have higher prostate-specific antigen (PSA) and longer time on first-line androgen receptor signaling inhibitors (ARSI). A total of 1,263 differentially expressed genes (DEGs) were identified and results of functional enrichment analysis indicated the enrichment in categories related to cell migration, cancer related pathways and metabolism. We identified the top 20 hub genes from the PPI network and analyzed the clinical characteristics correlated with these hub genes. Finally, we analyzed the immune cell abundance ratio of each sample in different groups. Our results reveal the different clinical characteristics, the immune cell infiltration pattern in different sites of mCRPC, and identify multiple critical related genes and pathways, which provides basis for individualized treatment.

scholarly journals Phase I Study of Samarium-153 Lexidronam With Docetaxel in Castration-Resistant Metastatic Prostate Cancer

2009 ◽  
Vol 27 (15) ◽  
pp. 2436-2442 ◽  
Author(s):  
Michael J. Morris ◽  
Neeta Pandit-Taskar ◽  
Jorge Carrasquillo ◽  
Chaitanya R. Divgi ◽  
Susan Slovin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Maximum Tolerated Dose ◽  
Resistant Disease ◽  
Castration Resistant ◽  
Bone Deposition ◽  
To Receive

Purpose Early studies of patients with castration-resistant metastatic prostate cancer (CRMPC) suggest that chemotherapy administered with a dose of a bone-seeking radiopharmaceutical is superior to chemotherapy alone. To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 (153Sm) lexidronam. Patients and Methods Men with progressive CRMPC were eligible. Cohorts of three to six patients were defined by dose escalations as follows: docetaxel 65, 70, 75, 75, 75 mg/m2 and 153Sm ethylenediaminetetramethylenephosphonate (EDTMP) 0.5, 0.5, 0.5, 0.75, 1 mCi/kg. Each cycle lasted a minimum of 6 (cohorts 1 through 5) or 9 (cohort 6) weeks. Docetaxel was administered on days 1 and 22 (and day 43 for cohort 6), and 153Sm-EDTMP was administered on day −1 to 1 of each cycle. Patients with acceptable hematologic toxicities were eligible to receive additional cycles until progression. Results Twenty-eight men were treated in six cohorts. Maximum-tolerated dose was not reached, because full doses of both agents were well tolerated, even using an every-6-week dosing schedule of 153Sm-EDTMP. Patients received an average of 5.6 docetaxel doses (range, one to 13 doses) and 2.9 153Sm-EDTMP doses (range, one to six doses). Fifteen patients demonstrated a more than 50% decline in prostate-specific antigen. Treatment significantly reduced indices of bone deposition and resorption. Conclusion Docetaxel and 153Sm-EDTMP can be combined safely at full doses over repeated cycles. Responses were seen in the small group of patients with taxane-resistant disease tested. The optimal phase II doses for patients with taxane-naïve disease may differ from those optimal for patients with taxane-resistant disease.

scholarly journals Clinical characteristics and outcomes for patients with non‑metastatic castration-resistant prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Peter Arnold ◽  
Maria Cristina Penaloza-Ramos ◽  
Lola Adedokun ◽  
Sarah Rees ◽  
Mohamed Lockhat ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Characteristics ◽  
Doubling Time ◽  
Specific Antigen ◽  
Proportional Hazard ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Cox Proportional Hazard ◽  
Psa Doubling Time ◽  
Cox Proportional Hazard Models

AbstractThis study used linked, routinely-collected datasets to explore incidence, clinical characteristics and outcomes of prostate cancer (PC) patients who experience a rise in prostate-specific antigen (PSA) levels despite androgen deprivation therapy (ADT), without evidence of metastases in their patient record, termed non-metastatic castration-resistant PC (nmCRPC). Routinely collected administrative data in Wales were used to identify patients diagnosed with PC and nmCRPC from 2000–2015. Logrank tests and Cox proportional hazard models were used to compare time-to-events across subgroups defined by PSA doubling time and age. Of 38,021 patients identified with PC, 1,465 met nmCRPC criteria. PC incidence increased over the study period, while nmCRPC categorizations reduced. Median time from PC diagnosis to nmCRPC categorization was 3.07 years (95% confidence interval [CI] 2.91–3.26) and from nmCRPC categorization to metastases/death was 2.86 years (95% CI 2.67–3.09). Shorter PSA doubling time (≤ 10 months, versus > 10 months) was associated with reduced time to metastases or death (2.11 years [95% CI 1.92–2.30] versus 5.22 years [95% CI 4.87–5.51]). Age was not significantly associated with time to metastases/death. Our findings highlight key clinical characteristics and outcomes for patients with nmCRPC prior to the introduction of recently approved treatments.

scholarly journals Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors

2021 ◽  
Author(s):  
Fred Saad ◽  
Martin Bögemann ◽  
Kazuhiro Suzuki ◽  
Neal Shore
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Imaging Techniques ◽  
Specific Antigen ◽  
Conventional Imaging ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Consensus Statements

Abstract Background Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit–risk profile of potential treatments is required. Methods In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function. Results and conclusions While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit–risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.

Bone modifying agents in veterans with castration-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6582-6582
Author(s):  
Jordan Bauman ◽  
Kyle Kumbier ◽  
Jennifer A. Burns ◽  
Jordan Sparks ◽  
Phoebe A. Tsao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Specific Antigen ◽  
Veterans Health ◽  
Health Administration ◽  
Castration Resistant Prostate Cancer ◽  
National Guidelines ◽  
Castration Resistant ◽  
Unit Increase

6582 Background: Skeletal related events (SREs) are a known complication for the 80% of men with metastatic prostate cancer who have bone metastases. Previous studies have demonstrated that bone modifying agents (BMAs) such as zoledronic acid and denosumab reduce SREs in men with metastatic castration-resistant prostate cancer who have bone metastases and are now recommended by national guidelines. We sought to investigate factors associated with use of BMAs in Veterans with CRPC across the Veterans Health Administration (VA). Methods: Using the VA Corporate Data Warehouse, consisting of aggregated medical record data from 130 facilities, we used an algorithm previously published to identify men with a diagnosis of castration-resistant prostate cancer (CRPC) based on rising prostate specific antigen (PSA) levels while on androgen deprivation therapy and who received systemic treatment for CRPC with one of the commonly used therapies: abiraterone, enzalutamide, docetaxel, ketoconazole between 2010 and 2017. To account for clustering among facilities, we used a multilevel multivariable logistic regression to determine the association of patient and disease-specific variables on the odds of a patient receiving a BMA after they started treatment for CRPC. Results: Of 4,998 patients with CRPC in our cohort, 2223 (44%) received either zoledronic acid or denosumab at some point after they were initiated on treatment for CRPC. After adjusting for other variables and accounting for a facility, the odds of receiving a BMA decreased by 3% for every additional year of age (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.96-0.98), and decreased significantly with increasing comorbid conditions (OR 0.94, 95% CI 0.72-0.98 for Charlson Comorbidity Index [CCI] of 1; OR 0.69, 95% CI 0.59-0.81 for CCI 2+). Patients who were Black had 25% lower odds of receiving a BMA than patients who were White (OR 0.75, 95% CI 0.65-0.87). PSA at time of CRPC treatment start had a small but not significant effect on receipt of a BMA (OR 1.04, 95% CI 1.00-1.08) for every unit increase of PSA on the log scale. PSA doubling time was not associated with receipt of a BMA. The presence of a diagnosis code for bone metastases was far lower than expected in this cohort of patients with CRPC (40.7%), and thus was not included in the model. We did not expect the presence of bone metastases to vary significantly among the other independent variables. Conclusions: Despite most patients with CRPC historically having bone metastases, less than half of patients with CRPC received a BMA. Patients who are older, had more comorbidities, or were Black were less likely to receive a BMA after starting treatment for CRPC. Understanding factors that lead to different patterns of treatment can guide initiatives toward more guideline-concordant care.

scholarly journals Who’s too old to screen? Prostate cancer in elderly men

2013 ◽  
Vol 3 (3) ◽  
pp. 205 ◽  
Author(s):  
Sandeep Mistry ◽  
Wesley Mayer ◽  
Rose Khavari ◽  
Gustavo Ayala ◽  
Brian Miles
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Threshold Value ◽  
The Elderly ◽  
Cancer De La Prostate ◽  
Gleason Grade ◽  
Elderly Men ◽  
Patients Âgés ◽  
Positive Core ◽  
Clinically Significant

Introduction: Prostate cancer is the most common nonskin malignancyaffecting men and is the second leading cause of cancerrelateddeath in North America. The incidence of prostate cancerincreases dramatically with age. However, many healthauthorities advocate the cessation of routine prostate cancer testingin men older than 75 because of the belief that most patientswill have a clinically insignificant cancer and will not benefit fromtherapy. The true prevalence of clinically significant prostate cancerin elderly men is not known.Methods: We analyzed 1446 needle biopsies of the prostate inmen aged 75 or older. All pathological reviews were conductedby the pathology department at the Methodist Hospital in Houston,Tex. Data were collected from pathology reports, hospital andclinic databases, and medical records when available. Dataobtained included age at biopsy, serum prostate-specific antigen(PSA) levels, number of positive core biopsies and Gleasongrade. Statistical analysis was performed using Stata. Clinicallysignificant cancer was defined by the pathological presence ofGleason grade 6 adenocarcinoma in more than 1 biopsy coreor the presence of any Gleason 4 or 5 component in the biopsy.Results: The median age of the patients included in the studywas 78.8 and 95% of the patients were between the ages of 75and 85. The mean serum PSA level for patients biopsied was10.4 μg/L. Of all biopsies reviewed, 53% were positive for prostatecancer and 78% of these would be defined as clinically significantcancer. Regression analysis revealed age to be a significant(p < 0.05) factor for increased Gleason grade in positive biopsies.Logistic regression revealed age as a significant factor (p <0.05) for clinically significant prostate cancer even when controllingfor PSA. A serum PSA threshold value of 6.5 μg/L would havemissed 38% of significant cancers and a threshold of 4.0 μg/Lwould have missed 8% of significant cancers.Conclusion: Our findings suggest that the prevalence of clinicallysignificant prostate cancer in the elderly population may be higherthan previously thought. As the population continues to livelonger and healthier lives, it will become more common to confrontprostate cancer morbidity in the eldery population. Usinghigher serum PSA thresholds to eliminate unnecessary biopsies inolder men does not appear to help identify patients at greaterrisk of having clinically significant prostate cancer. Patients withprostate cancer having aggressive clinical features may benefitfrom treatment of their prostate cancer well into their eighth andninth decades of life. Testing and diagnostic recommendationsshould reflect the potential benefit of identifying patients withaggressive prostate cancer even after age 75.Introduction : Le cancer de la prostate est le type de cancer noncutané le plus fréquent chez les hommes et la seconde causede décès lié au cancer en importance en Amérique du Nord.L’incidence du cancer de la prostate augmente grandement avecl’âge. Néanmoins, de nombreuses autorités en matière de santéavancent l’idée de mettre fin au dépistage systématique du cancerde la prostate chez les hommes de plus de 75 ans en raisonde la croyance selon laquelle la plupart des patients présenterontun cancer non significatif sur le plan clinique et ne bénéficierontpas d’un traitement. La véritable prévalence des cas decancer de la prostate cliniquement significatif chez les hommesâgés n’est pas établie.Méthodes : Nous avons analysé 1446 échantillons de biopsie àl’aiguille prélevés au niveau de la prostate chez des patients de75 ans ou plus. Toutes les analyses de pathologie ont été effectuéespar le service de pathologie du Methodist Hospital deHouston, au Texas. Les données ont été tirées des rapports depathologie, des bases de données des hôpitaux et des cliniques,et des dossiers médicaux lorsque possible. Les données obtenuesincluaient l’âge au moment de la biopsie, les valeurs d’antigèneprostatique spécifique (APS), le nombre de microbiopsies positiveset le score de Gleason. Les analyses statistiques ont été effectuéesà l’aide du système Stata. Le cancer cliniquement significatifest défini comme la présence d’un adénocarcinome avec un scorede Gleason de 6 dans plus d’une zone de biopsie ou un scorede Gleason de 4 ou 5 dans toute partie de l’échantillon.Résultats : L’âge moyen des patients inclus était de 78,8 ans et95 % des patients avaient entre 75 et 85 ans. La valeur moyennede l’APS chez les patients ayant subi une biopsie était de 10,4 μg/L.De tous les échantillons examinés, 53 % confirmaient la présenced’un cancer de la prostate, et le cancer était défini comme étantcliniquement significatif dans 78 % de ces cas. Une analyse derégression a révélé que l’âge était un facteur significatif (p <0,05) lié à un score de Gleason plus élevé dans les biopsies positives.Une analyse de régression logistique a révélé que l’âge étaitaussi un facteur significatif (p < 0,05) lié à un cancer de la prostatecliniquement significatif même en tenant compte du taux d’APS.Une valeur seuil d’APS de 6,5 μg/L serait passée à côté de 38 %des cas de cancer significatif, alors qu’une valeur seuil d’APSde 4,0 μg/L serait passée à côté de 8 % des cancers significatifs.Conclusion : Nos observations portent à croire que la prévalencedu cancer de la prostate significatif sur le plan clinique chezles patients âgés pourrait être plus élevée qu’on le croit. Avecl’augmentation de l’espérance de vie, l’incidence de la morbiditéliée au cancer de la prostate augmentera. Le recours àdes valeurs seuils d’APS plus élevées pour éliminer les cas debiopsies non nécessaires chez les hommes âgés ne semble pasaider à cerner les patients présentant un risque plus élevé de cancerde la prostate cliniquement significatif. Les patients atteintsde cancer de la prostate cliniquement agressif peuvent bénéficierd’un traitement contre le cancer même lorsqu’ils dépassentlargement les 80 ou les 90 ans. Les recommandations concernantle dépistage et le diagnostic devraient refléter les avantages potentielsliés au dépistage d’un cancer de la prostate agressif, mêmeaprès 75 ans.

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