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International Journal of Molecular... Aug 2023Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The... (Review)
Review
Epidemiological data highlight prostate cancer as a significant global health issue, with high incidence and substantial impact on patients' quality of life. The prevalence of this disease is associated with various factors, including age, heredity, and race. Recent research in prostate cancer genetics has identified several genetic variants that may be associated with an increased risk of developing the disease. However, despite the significance of these findings, genetic markers for prostate cancer are not currently utilized in clinical practice as reliable indicators of the disease. In addition to genetics, epigenetic alterations also play a crucial role in prostate cancer development. Aberrant DNA methylation, changes in chromatin structure, and microRNA (miRNA) expression are major epigenetic events that influence oncogenesis. Existing markers for prostate cancer, such as prostate-specific antigen (PSA), have limitations in terms of sensitivity and specificity. The cost of testing, follow-up procedures, and treatment for false-positive results and overdiagnosis contributes to the overall healthcare expenditure. Improving the effectiveness of prostate cancer diagnosis and prognosis requires either narrowing the risk group by identifying new genetic factors or enhancing the sensitivity and specificity of existing markers. Immunological biomarkers (both circulating and intra-tumoral), including markers of immune response and immune dysfunction, represent a potentially useful area of research for enhancing the diagnosis and prognosis of prostate cancer. Our review emphasizes the need for developing novel immunological biomarkers to improve the diagnosis, prognosis, and management of prostate cancer. We highlight the most recent achievements in the identification of biomarkers provided by circulating monocytes and tumor-associated macrophages (TAMs). We highlight that monocyte-derived and TAM-derived biomarkers can enable to establish the missing links between genetic predisposition, hormonal metabolism and immune responses in prostate cancer.
Topics: Male; Humans; Quality of Life; Prostatic Neoplasms; Biomarkers; Prostate-Specific Antigen; Epigenesis, Genetic
PubMed: 37628978
DOI: 10.3390/ijms241612797 -
European Journal of Nuclear Medicine... Jul 2023Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can...
Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [Lu]Lu-PSMA-617 and [Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals; Nuclear Medicine; Heterocyclic Compounds, 1-Ring; Dipeptides; Lutetium; Treatment Outcome
PubMed: 37246997
DOI: 10.1007/s00259-023-06255-8 -
Cancer Discovery Jan 2024Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing...
UNLABELLED
Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development.
SIGNIFICANCE
Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line mCRPC. This study provides proof of concept for T-cell engagers as a potential treatment for prostate cancer, validates STEAP1 as a target, and supports further clinical investigation of xaluritamig in prostate cancer. See related commentary by Hage Chehade et al., p. 20. See related article by Nolan-Stevaux et al., p. 90. This article is featured in Selected Articles from This Issue, p. 5.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Immunotherapy; Treatment Outcome; Antigens, Neoplasm; Oxidoreductases
PubMed: 37861461
DOI: 10.1158/2159-8290.CD-23-0964 -
Investigative and Clinical Urology Sep 2023
Topics: Male; Humans; Prostate-Specific Antigen; Early Detection of Cancer; Prostatic Neoplasms
PubMed: 37668197
DOI: 10.4111/icu.20230229 -
BMC Geriatrics Sep 2023Numerous studies have shown that the dietary inflammatory index (DII) is associated with adverse health effects. However, the relationship between DII and prostate...
BACKGROUND
Numerous studies have shown that the dietary inflammatory index (DII) is associated with adverse health effects. However, the relationship between DII and prostate cancer (PCa) remains controversial. Although alcohol is included in DII as a dietary factor, the various adverse health effects of alcohol consumption are not only related to inflammation. On the other hand, it has been a long-standing debate whether alcohol consumption is linked to the risk of PCa. Therefore, to clarify whether drinking affects the relationship between DII and PCa, we evaluated the correlation between DII and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database.
METHODS
We used data from the NHANES spanning from 2005 to 2010 to analyze the relationship between PCa and DII. Out of the 31,034 NHANES participants, we enrolled 4,120 individuals in our study, utilizing dietary intake data from a twenty-four-hour period to determine DII scores. Demographic data, physical and laboratory test results were collected to compare between low PSA and high PSA groups, and to calculate the odds ratio between both groups, we employed a logistic regression analysis.
RESULTS
In this cross-sectional investigation of PCa, drinkers and non-drinkers had different relationships between DII and PSA levels (OR: 1.2, 95% Cl: 1-1.44 vs. OR: 0.98, 95% Cl: 0.9-1.07), and DII and abstaining from alcohol were effective in reducing the incidence of PSA (p-value for significant interaction = 0.037).
CONCLUSION
The results of our study suggest that drinking may influence the relationship between DII and PSA levels. DII is likely to be a reliable indicator for estimating PSA levels among non-drinkers, who may limit their intake of pro-inflammatory ingredients to lower the incidence and death of PCa.
Topics: Male; Humans; Prostate-Specific Antigen; Cross-Sectional Studies; Nutrition Surveys; Diet; Ethanol; Drug-Related Side Effects and Adverse Reactions
PubMed: 37670257
DOI: 10.1186/s12877-023-04151-2 -
Clinical Cancer Research : An Official... Dec 2023Fibroblast activation protein (FAP) is a promising target for tumor treatment. In this study, we aimed to investigate the safety and efficacy of the albumin...
PURPOSE
Fibroblast activation protein (FAP) is a promising target for tumor treatment. In this study, we aimed to investigate the safety and efficacy of the albumin binder-conjugated FAP-targeted radiopharmaceutical, 177Lu-EB-FAPI (177Lu-LNC1004), in patients with metastatic radioiodine-refractory thyroid cancer (mRAIR-TC).
PATIENTS AND METHODS
This open-label, non-randomized, first-in-human, dose-escalation, investigator-initiated trial had a 3+3 design and involved a 6-week 177Lu-LNC1004 treatment cycle in patients with mRAIR-TC at 2.22 GBq initially, with subsequent cohorts receiving an incremental 50% dose increase until dose-limiting toxicity (DLT) was observed.
RESULTS
177Lu-LNC1004 administration was well tolerated, with no life-threatening adverse events observed. No patients experienced DLT in Group A (2.22 GBq/cycle). One patient experienced grade 4 thrombocytopenia in Group B (3.33 GBq/cycle); hence, another three patients were enrolled, none of whom experienced DLT. Two patients experienced grade 3 and 4 hematotoxicity in Group C (4.99 GBq/cycle). The mean whole-body effective dose was 0.17 ± 0.04 mSv/MBq. Intense 177Lu-LNC1004 uptake and prolonged tumor retention resulted in high mean absorbed tumor doses (8.50 ± 12.36 Gy/GBq). The mean effective half-lives for the whole-body and tumor lesions were 90.20 ± 7.68 and 92.46 ± 9.66 hours, respectively. According to RECIST, partial response, stable disease, and progressive disease were observed in 3 (25%), 7 (58%), and 2 (17%) patients, respectively. The objective response and disease control rates were 25% and 83%, respectively.
CONCLUSIONS
FAP-targeted radioligand therapy with 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated in patients with advanced mRAIR-TC, with high radiation dose delivery to the tumor lesions, encouraging therapeutic efficacy, and acceptable side effects.
Topics: Humans; Male; Iodine Radioisotopes; Thyroid Neoplasms; Radiopharmaceuticals; Prostate-Specific Antigen; Fibroblasts
PubMed: 37801296
DOI: 10.1158/1078-0432.CCR-23-1983 -
BMC Urology Jun 2023The incidence rate of prostate cancer (PCa) has continued to rise in Korea. This study aimed to construct and evaluate a 5-year PCa risk prediction model using a cohort...
INTRODUCTION
The incidence rate of prostate cancer (PCa) has continued to rise in Korea. This study aimed to construct and evaluate a 5-year PCa risk prediction model using a cohort with PSA < 10 ng/mL by incorporating PSA levels and individual factors.
METHODS
The PCa risk prediction model including PSA levels and individual risk factors was constructed using a cohort of 69,319 participants from the Kangbuk Samsung Health Study. 201 registered PCa incidences were observed. A Cox proportional hazards regression model was used to generate the 5-year risk of PCa. The performance of the model was assessed using standards of discrimination and calibration.
RESULTS
The risk prediction model included age, smoking status, alcohol consumption, family history of PCa, past medical history of dyslipidemia, cholesterol levels, and PSA level. Especially, an elevated PSA level was a significant risk factor of PCa (hazard ratio [HR]: 1.77, 95% confidence interval [CI]: [1.67-1.88]). This model performed well with sufficient discrimination ability and satisfactory calibration (C-statistic: 0.911, 0.874; Nam-D'Agostino test statistic:19.76, 4.21 in the development and validation cohort, respectively).
CONCLUSIONS
Our risk prediction model was effective in predicting PCa in a population according to PSA levels. When PSA levels are inconclusive, an assessment of both PSA and specific individual risk factors (e.g., age, total cholesterol, and family history of PCa) could provide further information in predicting PCa.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Proportional Hazards Models; Cholesterol; Biopsy; Risk Assessment
PubMed: 37270476
DOI: 10.1186/s12894-023-01259-w -
Clinical Genitourinary Cancer Dec 2023The associations among SARS-CoV-2 infection, vaccination and total serum prostate serum antigen (PSA) levels in men undergoing screening for prostate cancer are unknown.
INTRODUCTION
The associations among SARS-CoV-2 infection, vaccination and total serum prostate serum antigen (PSA) levels in men undergoing screening for prostate cancer are unknown.
METHODS
A retrospective analysis of data from a large health maintenance organization. Records of individuals aged 50 to 75 years with two serum PSA tests taken between March 2018 and November 2021 were included. Individuals with prostate cancer were excluded. Changes in PSA levels were compared between individuals who had at least 1 SARS-CoV-2 vaccination and/or infection between the two PSA tests and individuals who did not have an infection and were not vaccinated between the two PSA tests. Subgroup analyses were performed to assess the impact of the elapsed time between the event and the second PSA test on the results.
RESULTS
The study and control groups included 6,733 (29%) and 16 286 (71%) individuals, respectively. Although the median time between PSA tests was shorter in the study vs. the control group (440 vs. 469 days, P<.001), PSA elevation between the tests was higher in the study group (0.04 vs. 0.02, P<.001). The relative risk for PSA elevation ≥1 ng/dL was 1.22 (95% CI 1.1, 1.35). Among individuals who were vaccinated, PSA increased by 0.03 ng/dL (IQR -0.12, 0.28) and 0.09 ng/dL (IQR -0.05, 0.34) after 1 and 3 doses, respectively (P<.001). Multivariate linear regression showed that SARS-CoV-2 events (β 0.043; 95% CI 0.026-0.06) were associated with a greater risk for PSA elevation, after adjusting for age, baseline PSA and days between PSA tests.
CONCLUSION
SARS-CoV-2 infection and vaccinations are associated with a slight increase in PSA, with the third anti-COVID vaccine dose having a more prominent impact, but its clinical significance is unknown yet. Any significant increase in PSA must be investigated and cannot be dismissed as secondary to SARS-CoV-2 infection or vaccination.
Topics: Humans; Male; COVID-19; COVID-19 Vaccines; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; SARS-CoV-2; Vaccination
PubMed: 37270370
DOI: 10.1016/j.clgc.2023.05.001 -
Frontiers in Public Health 2023Oxidative Balance Score (OBS) is an index affecting the oxidative stress of dietary and lifestyle factors. We aimed to explore the association of OBS with prostate...
OBJECTIVE
Oxidative Balance Score (OBS) is an index affecting the oxidative stress of dietary and lifestyle factors. We aimed to explore the association of OBS with prostate specific antigen (PSA) among older males.
METHODS
A total of 5,136 samples were collected in this study to investigate the relationship between OBS and PSA from the National Health and Nutrition Examination Survey. Logistic regression models and restricted cubic spline were used to assess the associations between OBS and PSA.
RESULTS
Compared with the Q1 group, the odds ratios for the association between OBS and PSA were 1.005 (1.003, 1.009), 1.003 (1.001, 1.006), and 1.001 (0.978, 1.022) for Q2, Q3, and Q4, respectively. In the age-specific analyses, the association was significant among individuals aged 65 years old and over: the odds ratios for the association between OBS and PSA were 1.019 (1.005, 1.028), 1.028 (1.018, 1.039), and 1.038 (1.022, 1.049) for Q2, Q3, and Q4, respectively. But it was not significant among individuals aged less than 65 years old: the odds ratios for the association between OBS and PSA were 1.016 (0.995, 1.026), 1.015 (0.985, 1.022), and 0.988 (0.978, 1.016) for Q2, Q3, and Q4, respectively. The restricted cubic splines also indicated a nonlinear relationship between OBS and PSA among individuals aged 65 years old and over ( = 0.006, = 0.021).
CONCLUSION
Our findings provide evidence that OBS is positively associated with higher levels of PSA among older adults. Further large-scale prospective cohort studies are needed to verify our findings.
Topics: Aged; Humans; Male; Middle Aged; Diet; Nutrition Surveys; Oxidative Stress; Prospective Studies; Prostate-Specific Antigen
PubMed: 38317687
DOI: 10.3389/fpubh.2023.1336657