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BJU International Oct 2021To present an overview of radiation therapy (RT) for prostate cancer over the past decade. (Review)
Review
OBJECTIVES
To present an overview of radiation therapy (RT) for prostate cancer over the past decade.
METHODS
The literature on prostate cancer radiation therapy was reviewed and summarised. Radiation therapy (RT) for prostate cancer has dramatically evolved in the past decade, with superior techniques and exciting advances, pushing the role of the radiation oncologist to new frontiers.
RESULTS
Innovations in imaging, treatment delivery, and a deeper understanding of biology has resulted in more tailored RT for individuals. In the present review, we summarise the changing landscape and broadly discuss new developments in prostate RT.
CONCLUSIONS
Questions and challenges remain in the field, however there are multiple opportunities to further improve upon RT for our patients with prostate cancer.
Topics: Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Risk Assessment
PubMed: 34273237
DOI: 10.1111/bju.15550 -
The Journal of Urology Apr 2021We sought to identify new information evaluating clinically localized prostate cancer therapies. (Review)
Review
PURPOSE
We sought to identify new information evaluating clinically localized prostate cancer therapies.
MATERIALS AND METHODS
Bibliographic databases (2013-January 2020), ClinicalTrials.gov and systematic reviews were searched for controlled studies of treatments for clinically localized prostate cancer with duration ≥5 years for mortality and metastases, and ≥1 year for harms.
RESULTS
We identified 67 eligible references. Among patients with clinically, rather than prostate specific antigen, detected localized prostate cancer, watchful waiting may increase mortality and metastases but decreases urinary and erectile dysfunction vs radical prostatectomy. Comparative mortality effect may vary by tumor risk and age but not by race, health status, comorbidities or prostate specific antigen. Active monitoring probably results in little to no mortality difference in prostate specific antigen detected localized prostate cancer vs radical prostatectomy or external beam radiation plus androgen deprivation regardless of tumor risk. Metastases were slightly higher with active monitoring. Harms were greater with radical prostatectomy than active monitoring and mixed between external beam radiation plus androgen deprivation vs active monitoring. 3-Dimensional conformal radiation and androgen deprivation plus low dose rate brachytherapy provided small mortality reductions vs 3-dimensional conformal radiation and androgen deprivation but little to no difference on metastases. External beam radiation plus androgen deprivation vs external beam radiation alone may result in small mortality and metastasis reductions in higher risk disease but may increase sexual harms. Few new data exist on other treatments.
CONCLUSIONS
Radical prostatectomy reduces mortality vs watchful waiting in clinically detected localized prostate cancer but causes more harms. Effectiveness may be limited to younger men and those with intermediate risk disease. Active monitoring results in little to no mortality difference vs radical prostatectomy or external beam radiation plus androgen deprivation. Few new data exist on other treatments.
Topics: Comparative Effectiveness Research; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Watchful Waiting
PubMed: 33350857
DOI: 10.1097/JU.0000000000001578 -
PET Clinics Oct 2022Computed tomography (CT), MRI, and Ultrasound play an evolving role in prostate cancer management. Multi-parametric MRI has high sensitivity and negative predictive... (Review)
Review
Computed tomography (CT), MRI, and Ultrasound play an evolving role in prostate cancer management. Multi-parametric MRI has high sensitivity and negative predictive value in prostate cancer diagnosis, leading to increased utilization as part of an active surveillance paradigm in low-to-intermediate-risk patients, and local tumor staging in high-grade cancers. CT is modestly sensitive in staging high-grade tumors to evaluate for nodal, liver, lung, and bone metastasis, and is preferred for assessing treatment related complications. Until recently, ultrasound has been limited to a guidance modality for biopsy and treatment; however, advances in micro-ultrasound technology aim to expand its role diagnosing and managing prostate cancer.
Topics: Humans; Magnetic Resonance Imaging; Male; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Tomography, X-Ray Computed; Ultrasonography
PubMed: 36229101
DOI: 10.1016/j.cpet.2022.07.002 -
Minerva Urologica E Nefrologica = the... Oct 2020The aim of this review was to summarize the available evidence on the role of metastasis-directed therapy (MDT) and/or prostate-targeted therapy (PTT) in the setting of...
INTRODUCTION
The aim of this review was to summarize the available evidence on the role of metastasis-directed therapy (MDT) and/or prostate-targeted therapy (PTT) in the setting of oligometastatic prostate cancer (PCa).
EVIDENCE ACQUISITION
We searched PubMed, the Web of Science, and the Cochrane Library databases. The following keywords were used: ("prostate cancer" OR "prostate carcinoma" OR "prostate neoplasm" OR "prostate tumor") AND ("oligometastatic" OR "oligometastasis" OR "PSMA") AND ("surgery" OR "prostatectomy" OR "radical prostatectomy" OR "cytoreductive" OR "local treatment" OR "radiotherapy" OR "stereotactic" OR "stereotaxic") AND ("survival" OR "mortality").
EVIDENCE SYNTHESIS
After evaluating the selection criteria, 81 studies were evaluated for our endpoints. We included 22 studies for PTT of synchronous mPCa. There have been no randomized studies on cytoreductive prostatectomy (cRP). Four prospective studies showed that cRP was feasible but did not contribute to a positive effect on overall survival (OS). Regarding PTT-radiotherapy, two randomized controlled phase 3 trials showed that OS was improved in men with a low metastatic burden. Regarding MDT of metachronous lymph node recurrence, we included 29 retrospective studies. For MDT of oligometastases, we included 30 studies. One randomized phase 2 trial showed that androgen deprivation therapy-free survival improved with stereotactic body radiation therapy compared to that with surveillance; however, benefits on OS remain unclear.
CONCLUSIONS
We performed a comprehensive overview of the current literature on MDT and PTT. The feasibility of MDT and PTT is supported by several retrospective studies. Nevertheless, there remains a lack of high-quality trials to prove its survival benefits. Results from ongoing prospective trials data are awaited.
Topics: Humans; Male; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prostatic Neoplasms
PubMed: 32550632
DOI: 10.23736/S0393-2249.20.03779-0 -
Prostate Cancer and Prostatic Diseases Jun 2024Prostate cancer (PCa), one of the most prevalent malignancies affecting men, significantly contributes to increased mortality rates worldwide. While the causative death... (Review)
Review
BACKGROUND
Prostate cancer (PCa), one of the most prevalent malignancies affecting men, significantly contributes to increased mortality rates worldwide. While the causative death is due to advanced metastatic disease, this occurrence disproportionately impacts men of African descent compared to men of European descent. In this review, we describe potential mechanisms underlying PCa metastases disparities and current treatments for metastatic disease among these populations, differences in treatment outcomes, and survival rates, in hopes of highlighting a need to address disparities in PCa metastases.
METHODS
We reviewed existing literature using databases such as PubMed, Google Scholar, and Science Direct using the following keywords: "prostate cancer metastases", "metastatic prostate cancer disparity", "metastatic prostate cancer diagnosis and treatment", "prostate cancer genetic differences and mechanisms", "genetic differences and prostate tumor microenvironment", and "men of African descent and access to clinical treatments". The inclusion criteria for literature usage were original research articles and review articles.
RESULTS
Studies indicate unique genetic signatures and molecular mechanisms such as Epithelial-Mesenchymal Transition (EMT), inflammation, and growth hormone signaling involved in metastatic PCa disparities. Clinical studies also demonstrate differences in treatment outcomes that are race-specific, for example, patients of African descent have a better response to enzalutamide and immunotherapy yet have less access to these drugs as compared to patients of European descent.
CONCLUSIONS
Growing evidence suggests a connection between a patient's genetic profile, the prostate tumor microenvironment, and social determinants of health that contribute to the aggressiveness of metastatic disease and treatment outcomes. With several potential pathways highlighted, the limitations in current diagnostic and therapeutic applications that target disparity in PCa metastases warrant rigorous research attention.
Topics: Humans; Prostatic Neoplasms; Male; Neoplasm Metastasis; Tumor Microenvironment; Healthcare Disparities; Health Status Disparities; Epithelial-Mesenchymal Transition
PubMed: 37046071
DOI: 10.1038/s41391-023-00667-1 -
Cancer Radiotherapie : Journal de La... Oct 2021The management of high-risk prostate cancer has greatly evolved in recent years. Advances in imaging helps to better define the actual aggressiveness of the disease, to... (Review)
Review
The management of high-risk prostate cancer has greatly evolved in recent years. Advances in imaging helps to better define the actual aggressiveness of the disease, to plan the surgical procedure, and to improve the prognostic evaluation of this high-risk of recurrence disease. The information obtained by MRI and by targeted biopsies improves management before surgery. Advances in nuclear medicine and generalization of PSMA-PET scans are beginning to improve the initial stage of diagnosis, thanks to a better detection of lymph node and distant metastases. The oncological interest of these new imaging techniques, which then influence the therapeutic plan, remains to be defined. The curative impact of an extensive lymph node dissection, as currently recommended, remains to be proved, and recently published randomized trials do not provide firm conclusions. The new hormone therapies pave the way for an intensification of perioperative systemic treatment, with a significant action on the tumor tissue, but an impact on survival, which remains to be defined in the context of ongoing randomized trials.
Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Biopsy; Chemotherapy, Adjuvant; Humans; Lymph Node Excision; Lymph Nodes; Magnetic Resonance Imaging; Male; Neoplasm Recurrence, Local; Organ Sparing Treatments; Positron-Emission Tomography; Prognosis; Prostate; Prostatectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 34175227
DOI: 10.1016/j.canrad.2021.06.010 -
Molecular Cancer Research : MCR May 2022Treatment-induced tumor dormancy is a state in cancer progression where residual disease is present but remains asymptomatic. Dormant cancer cells are...
UNLABELLED
Treatment-induced tumor dormancy is a state in cancer progression where residual disease is present but remains asymptomatic. Dormant cancer cells are treatment-resistant and responsible for cancer recurrence and metastasis. Prostate cancer treated with androgen-deprivation therapy (ADT) often enters a dormant state. ADT-induced prostate cancer dormancy remains poorly understood due to the challenge in acquiring clinical dormant prostate cancer cells and the lack of representative models. In this study, we aimed to develop clinically relevant models for studying ADT-induced prostate cancer dormancy. Dormant prostate cancer models were established by castrating mice bearing patient-derived xenografts (PDX) of hormonal naïve or sensitive prostate cancer. Dormancy status and tumor relapse were monitored and evaluated. Paired pre- and postcastration (dormant) PDX tissues were subjected to morphologic and transcriptome profiling analyses. As a result, we established eleven ADT-induced dormant prostate cancer models that closely mimicked the clinical courses of ADT-treated prostate cancer. We identified two ADT-induced dormancy subtypes that differed in morphology, gene expression, and relapse rates. We discovered transcriptomic differences in precastration PDXs that predisposed the dormancy response to ADT. We further developed a dormancy subtype-based, predisposed gene signature that was significantly associated with ADT response in hormonal naïve prostate cancer and clinical outcome in castration-resistant prostate cancer treated with ADT or androgen-receptor pathway inhibitors.
IMPLICATIONS
We have established highly clinically relevant PDXs of ADT-induced dormant prostate cancer and identified two dormancy subtypes, leading to the development of a novel predicative gene signature that allows robust risk stratification of patients with prostate cancer to ADT or androgen-receptor pathway inhibitors.
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Androgens; Animals; Humans; Male; Mice; Neoplasm Recurrence, Local; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant
PubMed: 35082166
DOI: 10.1158/1541-7786.MCR-21-1037 -
The British Journal of Radiology Apr 2021We determined the sensitivity and specificity of multiparametric magnetic resonance imaging (MP-MRI) in detection of locally recurrent prostate cancer and extra...
OBJECTIVE
We determined the sensitivity and specificity of multiparametric magnetic resonance imaging (MP-MRI) in detection of locally recurrent prostate cancer and extra prostatic extension in the post-radical radiotherapy setting. Histopathological reference standard was whole-mount prostatectomy specimens. We also assessed for any added value of the dynamic contrast enhancement (DCE) sequence in detection and staging of local recurrence.
METHODS
This was a single centre retrospective study. Participants were selected from a database of males treated with salvage prostatectomy for locally recurrent prostate cancer following radiotherapy. All underwent pre-operative prostate-specific antigen assay, positron emission tomography CT, MP-MRI and transperineal template prostate mapping biopsy prior to salvage prostatectomy. MP-MRI performance was assessed using both Prostate Imaging-Reporting and Data System v. 2 and a modified scoring system for the post-treatment setting.
RESULTS
24 patients were enrolled. Using Prostate Imaging-Reporting and Data System v. 2, sensitivity, specificity, positive predictive value and negative predictive value was 64%, 94%, 98% and 36%. MP-MRI under staged recurrent cancer in 63%. A modified scoring system in which DCE was used as a co-dominant sequence resulted in improved diagnostic sensitivity (61%-76%) following subgroup analysis.
CONCLUSION
Our results show MP-MRI has moderate sensitivity (64%) and high specificity (94%) in detecting radio-recurrent intraprostatic disease, though disease tends to be under quantified and under staged. Greater emphasis on dynamic contrast images in overall scoring can improve diagnostic sensitivity.
ADVANCES IN KNOWLEDGE
MP-MRI tends to under quantify and under stage radio-recurrent prostate cancer. DCE has a potentially augmented role in detecting recurrent tumour compared with the setting. This has relevance in the event of any future modified MP-MRI scoring system for the irradiated gland.
Topics: Aged; Humans; Male; Middle Aged; Multiparametric Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Salvage Therapy; Sensitivity and Specificity
PubMed: 33586998
DOI: 10.1259/bjr.20201423 -
Annals of Medicine 2023Tumour classifications play a pivotal role in prostate cancer (PCa) management. It can predict the clinical outcomes of PCa as early as the disease is diagnosed and then... (Review)
Review
Tumour classifications play a pivotal role in prostate cancer (PCa) management. It can predict the clinical outcomes of PCa as early as the disease is diagnosed and then guide therapeutic schemes, such as active monitoring, standalone surgical intervention, or surgery supplemented with postoperative adjunctive therapy, thereby circumventing disease exacerbation and excessive treatment. Classifications based on clinicopathological features, such as prostate cancer-specific antigen, Gleason score, and TNM stage, are still the main risk stratification strategies and have played an essential role in standardized clinical decision-making. However, mounting evidence indicates that clinicopathological parameters in isolation fail to adequately capture the heterogeneity exhibited among distinct PCa patients, such as those sharing identical Gleason scores yet experiencing divergent prognoses. As a remedy, molecular classifications have been introduced. Currently, molecular studies have revealed the characteristic genomic alterations, epigenetic modulations, and tumour microenvironment associated with different types of PCa, which provide a chance for urologists to refine the PCa classification. In this context, numerous invaluable molecular classifications have been devised, employing disparate statistical methodologies and algorithmic approaches, encompassing self-organizing map clustering, unsupervised cluster analysis, and multifarious algorithms. Interestingly, the classifier PAM50 was used in a phase-2 multicentre open-label trial, NRG-GU-006, for further validation, which hints at the promise of molecular classification for clinical use. Consequently, this review examines the extant molecular classifications, delineates the prevailing panorama of clinically pertinent molecular signatures, and delves into eight emblematic molecular classifications, dissecting their methodological underpinnings and clinical utility.
Topics: Male; Humans; Prostatic Neoplasms; Prognosis; Prostate-Specific Antigen; Neoplasm Grading; Risk Assessment; Tumor Microenvironment
PubMed: 37939258
DOI: 10.1080/07853890.2023.2279235 -
Urology Journal Feb 2024Prostate cancer (PCa) is the second most commonly diagnosed cancer and the sixth leading cause of cancer death among men worldwide. Biomarkers are an important tool in... (Review)
Review
PURPOSE
Prostate cancer (PCa) is the second most commonly diagnosed cancer and the sixth leading cause of cancer death among men worldwide. Biomarkers are an important tool in the early detection of PCa. Prostate-specific antigen (PSA) is one of the oldest biomarkers for the early detection of PCa. Digital rectal exam (DRE) is another screening test for PCa detection, which is considered as an irritating experience for patients. Biopsy is still the most reliable method for PCa diagnosis; however, patients are prone to complications. Therefore, developing non-invasive and accurate methods for PCa screening seems urgent to avoid unnecessary biopsies. There has been remarkable development in PCa molecular biomarkers discovery, largely through progress in omics technologies. Due to the many benefits of liquid biopsies, a significant set of PCa diagnostic kits have been developed using urine samples. Despite the unique benefits of these kits, there are still many challenges to their widespread use in clinics. Here, we have reviewed the latest developments of PCa biomarkers in liquid biopsies.
METHODS
Literature on biomarkers for diagnosis of PCa was reviewed during the past two decades.
RESULTS
PSA, PHI, PCA3, and 4K score are among the commonly used markers for PCa diagnosis which have been used over a long-moderate length of time with multiple studies on their performance. We performed a review of their performance. Newer markers are among RNA and DNA markers. Multiple non-coding RNAs (mi-RNAs) were reviewed and their performance on Pca diagnosis was reviewed. Long noncoding RNAs (Lnc RNAs) including PlncRNA-1, HOTAIR, SchLAP-1, MALAT1, MEG3, and PRCAT17.3 were summarized. mRNA markers including TMPRSS2:ERG, and HOXC6 were presented. DNA-based markers including PTEN, HOXB13, and BRCA2 were reviewed. Finally, the use of CircRNAs was reviewed for PCa diagnosis.
CONCLUSION
Many reviewed RNA-based biomarkers have promising results in the diagnosis of PCa.
Topics: Male; Humans; Prostate-Specific Antigen; Biomarkers, Tumor; Antigens, Neoplasm; Prostatic Neoplasms; RNA
PubMed: 37818554
DOI: 10.22037/uj.v20i.7687