Oligometastatic prostate cancer: is it worth targeting the tip of the iceberg?
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ABSTRACT:
SUBMITTER: Supiot S
PROVIDER: S-EPMC8799158 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Prostate cancer (PCA) is the most-prevalent non-skin cancer in men worldwide. Nevertheless, the treatment of oligometastatic, especially lymph-node (ln) recurrent, PCA remains elusive. The aim of our study was to provide insights in radiotherapy (RT)-treatment of recurrent PCA exhibiting ln- or osseous (oss)-oligometastases. METHODS:Between April 2012 and April 2017, 27 oligometastatic PCA patients (19 ln and 8 single oss) were treated with RT at our institution. RESULTS:The metastasis-free survival (MFS) was 24.8 m (22.0-36.0 m) and 25.4 m (23.9-28.1 m) for the ln- and oss-subgroup resulting in 1-year MFS of 75.4 and 100% and 2-year MFS of 58.7 and 83.3% for ln- and oss-metastatic patients, respectively. Of notice, none of the recurrences for ln-patients was in the RT-field, constituting a local control of 100%. Within the ln-group, pre-RT median-PSA was 2.6 ng/ml, median post-RT PSA was 0.3 ng/ml, which was significant (p?=?0.003). Median biochemical-free survival (bfS) was 12.2 m. PCA that was initially confined to the prostate had a better bfS (p?<?0.001) and MFS (p?=?0.013). The oss-group had a median PSA of 4.9 ng/ml pre-treatment which dropped to a median value of 0.14 ng/ml (p?=?0.004). Toxicities were moderate, with only 1 case of III° toxicity. There were no deaths in the ln-group, thus overall survial was 100% here. CONCLUSION:Our study points out the feasibility of RT as a treatment option in recurrent PCA and demonstrates an excellent local control with a low-toxicity profile.
| S-EPMC6150968 | biostudies-literature
Project description:Purpose of reviewMetastatic castration-resistant prostate cancer is in critical need of new and innovative treatment strategies. Since the approval of sipuleucel-T, the investigatory climate of prostate cancer immunotherapy has been rapidly evolving with promising developments in vaccine and immune checkpoint therapies.Recent findingsSipuleucel-T remains the first and only therapeutic cancer vaccine approved for its survival benefit in metastatic castration-resistant prostate cancer. Additional cancer vaccines are currently being evaluated, with the most promising being a peptide vaccine encoding prostate-specific antigen, known as prostate-specific antigen-TRICOM. Emerging data supports combinatorial strategies for vaccine therapy and a potential role for implementation in earlier stages of advanced disease. Immune checkpoint therapies have demonstrated limited success in prostate cancer with negative late phase trials for ipilimumab monotherapy and discouraging early phase results for programmed cell death protein 1 blockade. Novel immune-modulatory targets and rational combination strategies aim to produce more favorable results. Recent progress has been made to determine biologic predictors for response and toxicity in prostate cancer immunotherapy aiming to improve patient selection and safety.SummarySteady progress is anticipated in the field of prostate cancer immunotherapy including ongoing development of novel cancer vaccines, immune checkpoint therapies, and combinatorial strategies.
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Project description:The mainstay of treatment for men with three or fewer non-castrate metastatic lesions outside of the prostate remains morbid palliative androgen deprivation therapy. We believe there is now a significant body of retrospective literature to suggest a survival benefit if these men have radical treatment to their primary tumour alongside 'metastasis-directed therapy' to the metastatic deposits. However, this regimen should be reserved to high-volume centres with quality assurance programmes and excellent outcomes. Patients should be made clear as to the uncertainty of benefit for this multi-site treatment strategy, and we await the publication of randomised controlled trials reporting in the next 5 years.
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Project description:Purpose of reviewTo analyze recent trials of upfront chemotherapy to determine how this paradigm can be applied to oligometastatic prostate cancer patients.Recent findingsUpfront chemotherapy prolongs survival in metastatic prostate cancer, according to the ChemoHormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer and STAMPEDE docetaxel trials. However, the benefit is driven by the high volume subset and may not apply to low-volume/oligometastatic patients.SummaryOligometastatic patients may not all share the same biology. Advanced imaging techniques may help to more accurately identify truly oligometastatic patients. Molecular markers will be necessary to distinguish oligometastatic patients who fare well enough with androgen deprivation therapy alone as opposed to those for whom upfront chemotherapy may be beneficial. Emerging molecular markers of docetaxel sensitivity, such as loss of lysine-specific demethylase 5d, warrant prospective validation with one goal of identifying oligometastatic patients with greatest likelihood of benefit from this strategy.
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Project description:Botulinum neurotoxins (BoNTs), the etiological agents of botulism, are the deadliest toxins known to humans. Yet, thanks to their biological and toxicological features, BoNTs have become sophisticated tools to study neuronal physiology and valuable therapeutics for an increasing number of human disorders. BoNTs are produced by multiple bacteria of the genus Clostridium and, on the basis of their different immunological properties, were classified as seven distinct types of toxin. BoNT classification remained stagnant for the last 50 years until, via bioinformatics and high-throughput sequencing techniques, dozens of BoNT variants, novel serotypes as well as BoNT-like toxins within non-clostridial species have been discovered. Here, we discuss how the now “booming field” of botulinum neurotoxin may shed light on their evolutionary origin and open exciting avenues for future therapeutic applications.
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Project description:Marine viruses are the most abundant biological entity in the oceans, the majority of which infect bacteria and are known as bacteriophages. Yet, the bulk of bacteriophages form part of the vast uncultured dark matter of the microbial biosphere. In spite of the paucity of cultured marine bacteriophages, it is known that marine bacteriophages have major impacts on microbial population structure and the biogeochemical cycling of key elements. Despite the ecological relevance of marine bacteriophages, there are relatively few isolates with complete genome sequences. This minireview focuses on knowledge gathered from these genomes put in the context of viral metagenomic data and highlights key advances in the field, particularly focusing on genome structure and auxiliary metabolic genes.
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Project description: Not available
| S-EPMC8246027 | biostudies-literature
Project description:PURPOSE:Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. METHODS:A literature search on December 15th 2017 was conducted using the Pubmed database. RESULTS:Functional imaging techniques like 68Ga PSMA. 68Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. CONCLUSIONS:Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.
| S-EPMC6868105 | biostudies-literature
Project description:Purpose of reviewTo summarize the recent findings on the subject of metastasis-directed therapy (MDT) in the treatment of oligometastatic prostate cancer (omPCa).Recent findingsEvidence from two randomized clinical trials (RCTs) and a meta-analysis show favorable toxicity profiles, and the potential to delay androgen-deprivation therapy (ADT) for up to two years in nearly half of patients with metachronous hormone-sensitive omPCa. Another RCT showed promising results of MDT as treatment-escalation method combined with androgen receptor signaling inhibitors (ARSI) in first-line treatment for castration-resistant omPCa.Surveys by radiation oncologists and consensus guidelines advocate for MDT across various omPCa scenarios. Multiple single-arm trials present encouraging results; however, the evidence for the benefit of MDT is still weak requiring further investigation to assess its impact on pivotal endpoints, such as survival and quality of life.SummaryMDT is a promising approach in omPCa, and can be used to defer ADT in newly diagnosed metachronous omPCa patients, or to add to ARSI treatment at first diagnosis of castration-resistance. Ongoing prospective trials are needed to guide its optimal utilization in other settings, and patients should be informed about the evolving landscape of systemic therapies with proven survival benefits alongside MDT options.
| S-EPMC10990025 | biostudies-literature
Project description:Oligometastatic prostate cancer is an evolving clinical entity as more data from novel imaging tools such as PSMA PET/CT emerges. Recognition of this disease entity allows for unique interventions which differ from conventional treatment of metastatic prostate cancers such as the initiation of chemotherapy. With metastasis-directed therapy (MDT), there is potential for early eradication of limited disease metastases and a delay in systemic treatment with its associated treatment-related toxicities. This review explores the current evidence and outcomes of different metastasis-directed therapies such as the role of radiotherapy in low volume metastasis and the use of PSMA ligands to facilitate pelvic lymph node dissections. With a deeper understanding of this low metastasis state, it has revolutionized the current viable treatment options, and more studies are ongoing to provide further insights into this unique disease entity.
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