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Investigative and Clinical Urology Jul 2023
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen; Early Detection of Cancer; Mass Screening
PubMed: 37417555
DOI: 10.4111/icu.20230178 -
Current Oncology Reports Feb 2024Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European... (Review)
Review
PURPOSE OF REVIEW
Prostate cancer is the most frequently diagnosed non-cutaneous malignancy of men in the USA; notably, the incidence is higher among men of African, followed by European and Asian ancestry. Germline mutations and, in particular, mutations in DNA damage repair genes (DDRGs) have been implicated in the pathogenesis of prostate cancer. This review intends to discuss the implication of ancestry on prostate cancer, specifically in regard to lack of diversity in genomic and genetic databases and the ability of providers to properly counsel patients on the significance of cancer genetic results.
RECENT FINDINGS
Ancestral differences in prostate cancer-associated DDRG germline mutations are increasingly recognized. Guidelines for treatment by the National Comprehensive Cancer Network® (NCCN®) support germline testing in certain patients, and a myriad of genetic testing panels for DDRG mutations are now available in clinical practice. However, the consensus among providers on what genes and mutations to include in the genetic tests has evolved from experience from men of European ancestry (EA). Gaps in ancestry-informed clinical practice exist in genetic risk assessment, implementation of screening, counseling, guiding recommendations, treatment, and clinical trial enrollment. The lack of diversity in tumor genomic and genetic databases may hinder ancestry-specific disease-predisposing alterations from being discovered and targeted in prostate cancer and, therefore, impede the ability of providers to accurately counsel patients on the significance of cancer genetic test results.
Topics: Male; Humans; Germ-Line Mutation; Prostatic Neoplasms; Mutation; Genetic Testing; Genetic Predisposition to Disease
PubMed: 38265515
DOI: 10.1007/s11912-024-01493-x -
Nutrients Mar 2024Cancer has become a serious problem worldwide, as it represents the main cause of death, and its incidence has increased over the years. A potential strategy to counter... (Review)
Review
Cancer has become a serious problem worldwide, as it represents the main cause of death, and its incidence has increased over the years. A potential strategy to counter the growing spread of various forms of cancer is the adoption of prevention strategies, in particular, the use of healthy lifestyles, such as maintaining a healthy weight, following a healthy diet; being physically active; avoiding smoking, alcohol consumption, and sun exposure; and vitamin D supplementation. These modifiable risk factors are associated with this disease, contributing to its development, progression, and severity. This review evaluates the relationship between potentially modifiable risk factors and overall cancer development, specifically breast, colorectal, and prostate cancer, and highlights updated recommendations on cancer prevention. The results of numerous clinical and epidemiological studies clearly show the influence of lifestyles on the development and prevention of cancer. An incorrect diet, composed mainly of saturated fats and processed products, resulting in increased body weight, combined with physical inactivity, alcohol consumption, and smoking, has induced an increase in the incidence of all three types of cancer under study. Given the importance of adopting correct and healthy lifestyles to prevent cancer, global institutions should develop strategies and environments that encourage individuals to adopt healthy and regular behaviors.
Topics: Male; Humans; Risk Factors; Diet; Healthy Lifestyle; Alcohol Drinking; Life Style; Prostatic Neoplasms
PubMed: 38542712
DOI: 10.3390/nu16060800 -
Molecular Cancer Research : MCR May 2024Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into...
UNLABELLED
Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into emergent aggressive variant prostate cancer (AVPC), which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflect and retain key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. We compared 15 NE versus 33 AdCa samples, which included six different PDX tumors for each group in biological replicates, and identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of concordance from PDX tumor-matched protein and mRNA revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa.
IMPLICATIONS
Overall, our study highlights the importance of protein-based identification when compared with RNA and provides a rich resource of new and feasible targets for clinical assay development and in understanding the underlying biology of these tumors.
Topics: Humans; Male; Proteome; Animals; Mice; Phosphoproteins; Prostatic Neoplasms, Castration-Resistant; Heterografts; Prostatic Neoplasms; Adenocarcinoma; Xenograft Model Antitumor Assays; Proteomics
PubMed: 38345532
DOI: 10.1158/1541-7786.MCR-23-0976 -
Prostate Cancer and Prostatic Diseases Dec 2023
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Diet, Healthy; Diet; Life Style
PubMed: 36732362
DOI: 10.1038/s41391-023-00651-9 -
European Urology Oct 2023Considering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial. (Randomized Controlled Trial)
Randomized Controlled Trial
A Detailed Evaluation of the Effect of Prostate-specific Antigen-based Screening on Morbidity and Mortality of Prostate Cancer: 21-year Follow-up Results of the Rotterdam Section of the European Randomised Study of Screening for Prostate Cancer.
BACKGROUND
Considering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial.
OBJECTIVE
To provide an update on the effect of prostate-specific antigen (PSA)-based screening on PCa-specific mortality (PCSM), metastatic disease, and overdiagnosis in the Dutch arm of the ERSPC.
DESIGN, SETTING, AND PARTICIPANTS
Between 1993 and 2000, a total of 42376 men, aged 55-74 yr, were randomised to a screening or a control arm. The main analysis was performed with men aged 55-69 yr (n = 34831). Men in the screening arm were offered PSA-based screening with an interval of 4 yr.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Intention-to-screen analyses with Poisson regression were used to calculate rate ratios (RRs) of PCSM and metastatic PCa.
RESULTS AND LIMITATIONS
After a median follow-up of 21 yr, the RR of PCSM was 0.73 (95% confidence interval [CI]: 0.61-0.88) favouring screening. The numbers of men needed to invite (NNI) and needed to diagnose (NND) to prevent one PCa death were 246 and 14, respectively. For metastatic PCa, the RR was 0.67 (95% CI: 0.58-0.78) favouring screening. The NNI and NND to prevent one metastasis were 121 and 7, respectively. No statistical difference in PCSM (RR of 1.18 [95% CI: 0.87-1.62]) was observed in men aged ≥70 yr at the time of randomisation. In the screening arm, higher rates of PCSM and metastatic disease were observed in men who were screened only once and in a selected group of men above the screening age cut-off of 74 yr.
CONCLUSIONS
The current analysis illustrates that with a follow-up of 21 yr, both absolute metastasis and mortality reduction continue to increase, resulting in a more favourable harm-benefit ratio than demonstrated previously. These data do not support starting screening at the age of 70-74 yr and show that repeated screening is essential.
PATIENT SUMMARY
Prostate-specific antigen-based prostate cancer screening reduces metastasis and mortality. Longer follow-up shows fewer invitations and diagnoses needed to prevent one death, a positive note towards the issue of overdiagnosis.
Topics: Humans; Male; Early Detection of Cancer; Follow-Up Studies; Mass Screening; Morbidity; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 37029074
DOI: 10.1016/j.eururo.2023.03.016 -
BMJ Open Oct 2023Patients undergoing prostate radiotherapy with an enlarged prostate can have short-term and long-term urinary complications. Currently, transurethral resection of the...
mparing Urolift and tandard ransurethral resection of prostate head of adiotherapy in men with urinary symptoms secondary to prostate enlargement in Southwest London and North Cumbria (CO-STAR): a study protocol for a randomised feasibility study.
INTRODUCTION
Patients undergoing prostate radiotherapy with an enlarged prostate can have short-term and long-term urinary complications. Currently, transurethral resection of the prostate (TURP) is the mainstay surgical intervention for men with urinary symptoms due to an enlarged prostate prior to radiotherapy. UroLift (NeoTract, Pleasanton, CA, USA) is a recent minimally invasive alternative, widely used in benign disease but is untested in men with prostate cancer.
METHODS AND ANALYSIS
A multicentre, two-arm study designed in collaboration with a Patient Reference Group to assess the feasibility of randomising men with prostate cancer and coexisting urinary symptoms due to prostate enlargement to TURP or UroLift ahead of radiotherapy. 45 patients will be enrolled and randomised (1:1) using a computer-generated programme to TURP or UroLift. Recruitment and retention will be assessed over a 12 month period. Information on clinical outcomes, adverse events and costs will be collected. Clinical outcomes and patient reported outcome measures will be measured at baseline, 6 weeks postintervention and 3 months following radiotherapy. A further 12 in-depth interviews will be conducted with a subset of patients to assess acceptability using the Theoretical Framework of Acceptability. Descriptive analysis on all outcomes will be performed using Stata (StataCorp V.2021).
ETHICS AND DISSEMINATION
The trial has been approved by the Research Ethics Committee (REC) NHS Health Research Authority (HRA) and Health and Care Research Wales (HCRW). The results will be published in peer-reviewed journals, presented at national meetings and disseminated to patients via social media, charity and hospital websites.
TRIAL REGISTRATION NUMBER
NCT05840549.
Topics: Humans; Male; Feasibility Studies; London; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Transurethral Resection of Prostate; Randomized Controlled Trials as Topic
PubMed: 37802612
DOI: 10.1136/bmjopen-2023-076621 -
Current Treatment Options in Oncology Feb 2024PSMA-PET has been a practice-changing imaging biomarker for the management of men with PCa. Research suggests improved accuracy over conventional imaging and other PET... (Review)
Review
PSMA-PET has been a practice-changing imaging biomarker for the management of men with PCa. Research suggests improved accuracy over conventional imaging and other PET radiotracers in many contexts. With multiple approved PSMA-targeting radiotracers, PSMA PET will become even more available in clinical practice. Its increased use requires an understanding of the prospective data available and caution when extrapolating from prior trial data that utilized other imaging modalities. Future trials leveraging PSMA PET for treatment optimization and management decision-making will ultimately drive its clinical utility.
Topics: Humans; Male; Antigens, Surface; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Prospective Studies; Prostatic Neoplasms; Radiopharmaceuticals; Prostate-Specific Antigen
PubMed: 38270802
DOI: 10.1007/s11864-024-01181-9 -
Biochimica Et Biophysica Acta. Reviews... Mar 2024Prostate cancer is unique compared to other major cancers due to the presence of multiple primary malignant foci in the majority of patients at the time of diagnosis.... (Review)
Review
Prostate cancer is unique compared to other major cancers due to the presence of multiple primary malignant foci in the majority of patients at the time of diagnosis. Each malignant focus has distinct somatic mutations and gene expression patterns, which represents a challenge for the development of prognostic tests for localized prostate cancer. Additionally, the molecular heterogeneity of advanced prostate cancer has important implications for management, particularly for patients with metastatic and locally recurrent cancer. Studies have shown that prostate cancers with mutations in DNA damage response genes are more sensitive to drugs inhibiting the poly ADP-ribose polymerase (PARP) enzyme. However, testing for such mutations should consider both spatial and temporal heterogeneity. Here, we summarize studies where multiregional genomics and transcriptomics analyses have been performed for primary prostate cancer. We further discuss the vast interfocal heterogeneity and how prognostic biomarkers and a molecular definition of the index tumor should be developed. The concept of focal treatments in prostate cancer has been evolving as a demand from patients and clinicians and is one example where there is a need for defining an index tumor. Here, biomarkers must have proven value for individual malignant foci. The potential discovery and implementation of biomarkers that are agnostic to heterogeneity are also explored as an alternative to multisample testing. Thus, deciding upon whole-organ treatment, such as radical prostatectomy, should depend on information from biomarkers which are informative for the whole organ.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Mutation; Prostatectomy; Biomarkers
PubMed: 38272101
DOI: 10.1016/j.bbcan.2024.189080 -
The Journal of Clinical Investigation Nov 2023Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3β-hydroxysteroid...
Half of all men with advanced prostate cancer (PCa) inherit at least 1 copy of an adrenal-permissive HSD3B1 (1245C) allele, which increases levels of 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) and promotes intracellular androgen biosynthesis. Germline inheritance of the adrenally permissive allele confers worse outcomes in men with advanced PCa. We investigated whether HSD3B1 (1245C) drives resistance to combined androgen deprivation and radiotherapy. Adrenally permissive 3βHSD1 enhanced resistance to radiotherapy in PCa cell lines and xenograft models engineered to mimic the human adrenal/gonadal axis during androgen deprivation. The allele-specific effects on radiosensitivity were dependent on availability of DHEA, the substrate for 3βHSD1. In lines expressing the HSD3B1 (1245C) allele, enhanced expression of DNA damage response (DDR) genes and more rapid DNA double-strand break (DSB) resolution were observed. A correlation between androgen receptor (AR) expression and increased DDR gene expression was confirmed in 680 radical prostatectomy specimens. Treatment with the nonsteroidal antiandrogen enzalutamide reversed the resistant phenotype of HSD3B1 (1245C) PCa in vitro and in vivo. In conclusion, 3βHSD1 promotes prostate cancer resistance to combined androgen deprivation and radiotherapy by upregulating DNA DSB repair. This work supports prospective validation of early combined androgen blockade for high-risk men harboring the HSD3B1 (1245C) allele.
Topics: Humans; Male; Androgen Antagonists; Androgens; DNA; Genotype; Hydroxysteroid Dehydrogenases; Multienzyme Complexes; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 37966114
DOI: 10.1172/JCI165718