scholarly journals A A Canadian consensus forum on the management of patients with advanced prostate cancer

2019 ◽  
Vol 14 (4) ◽  
Author(s):  
Fred Saad ◽  
Christina Canil ◽  
Antonio Finelli ◽  
Sebastien J. Hotte ◽  
Shawn Malone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Research Education ◽  
Modified Delphi ◽  
Castration Resistant ◽  
Medical Oncologists ◽  
Oligometastatic Prostate Cancer ◽  
Scientific Group ◽  
High Level

Introduction: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa. Methods: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians). Results: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC. Conclusions: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

scholarly journals Canadian consensus forum of key controversial areas in the management of advanced prostate cancer

2021 ◽  
Vol 15 (10) ◽  
Author(s):  
Fred Saad ◽  
Sebastien J Hotte ◽  
Antonio Finelli ◽  
Shawn Malone ◽  
Tamim Niazi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Ad Hoc ◽  
Consensus Conference ◽  
Castration Resistant ◽  
Medical Oncologists ◽  
Research And Education ◽  
Research Consortium ◽  
High Level ◽  
Management Choice

Introduction: Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) have created areas where high-level evidence to guide practice is lacking. The Genitourinary Research Consortium (GURC) conducted its second Canadian consensus forum to address areas of controversy in the management of PCa and provide recommendations to guide treatment. Methods: A panel of PCa specialists discussed topics related to the management of PCa. The core scientific committee finalized the design, questions and the analysis of the consensus results. Attendees then voted to indicate their management choice regarding each statement/topic. Questions for voting were adapted from the 2019 Advanced Prostate Cancer Consensus Conference. The thresholds for agreement were set at ≥ 75% for ‘consensus agreement’, > 50% for “near-consensus”, and ≤ 50% for “no consensus”. Results: The panel was comprised of 29 PCa experts including urologists (n=12), medical oncologists (n= 12), and radiation oncologists (n= 5). Voting took place for 65 pre-determined questions and three ad hoc questions. Consensus was reached for 34 questions, spanning a variety of areas including biochemical recurrence, treatment of metastatic castration-sensitive PCa, management of non-metastatic and metastatic castration-resistant PCa, bone health, and molecular profiling. Conclusions: The consensus forum identified areas of consensus or near-consensus in more than half of the questions discussed. Areas of consensus typically aligned with available evidence, and areas of variability may indicate a lack of high-quality evidence and point to future opportunities for further research and education.

Genomic analysis of circulating tumor DNA in 3,334 patients with advanced prostate cancer to identify targetable BRCA alterations and AR resistance mechanisms.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 25-25
Author(s):  
Hanna Tukachinsky ◽  
Russell Madison ◽  
Jon Chung ◽  
Lucas Dennis ◽  
Bernard Fendler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Acquired Resistance ◽  
Genomic Analysis ◽  
Circulating Tumor Dna ◽  
Resistance Mechanisms ◽  
Cancer Tissue ◽  
Castration Resistant Prostate Cancer ◽  
High Level ◽  
Tumor Dna

25 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) from plasma provides a minimally invasive method to identify targetable genomic alterations (GAs) and resistance mechanisms in patients with metastatic castration-resistant prostate cancer (mCRPC). The circulating tumor fraction in patients with mCRPC and the clinical validity of GAs detected in plasma remain unknown. We evaluated the landscape of GAs using ctDNA-based CGP and assessed concordance with tissue-based CGP. Methods: Plasma from 3,334 patients with advanced prostate cancer (including 1,674 mCRPC screening samples from the TRITON2/3 trials and 1,660 samples from routine clinical CGP) was analyzed using hybrid-capture-based gene panel NGS assays. Results were compared with CGP of 2,006 metastatic prostate cancer tissue biopsies. Concordance was evaluated in 837 patients with both tissue (archival or contemporaneous) and plasma NGS results. Results: 3,127 patients [94%] had detectable ctDNA. BRCA1/2 were mutated in 295 patients [8.8%]. In concordance analysis, 72/837 [8.6%] patients had BRCA1/2 mutations detected in tissue, 67 [93%] of whom were also identified by ctDNA, and 20 patients were identified using ctDNA but not tissue [23% of all patients identified using ctDNA]. ctDNA detected subclonal BRCA1/2 reversions in 10 of 1,660 [0.6%] routine clinical CGP samples. AR alterations, including amplifications and hotspot mutations, which were detected in 940/2,213 patients [42%]. Rare AR compound mutations, rearrangements, and novel in-frame deletions were identified. Altered pathways included PI3K/AKT/mTOR [14%], WNT/β-catenin [17%], and RAS/RAF/MEK [5%]. Microsatellite instability was detected in 31/2,213 patients [1.4%]. Conclusions: In the largest study of mCRPC plasma samples conducted to date, CGP of ctDNA recapitulated the genomic landscape detected in tissue biopsies, with a high level of agreement in detection of BRCA1/2 alterations. It also identified patients who may have gained somatic BRCA1/2 alterations since archival tissue was collected. ctDNA detected more acquired resistance GAs than tissue, including novel AR-activating variants. The large percentage of patients with rich genomic signal from ctDNA, and the sensitive, specific detection of BRCA1/2 alterations position liquid biopsy as a compelling clinical complement to tissue CGP for patients with mCRPC.

scholarly journals The Current Landscape of Treatment in Non-Metastatic Castration-Resistant Prostate Cancer

2019 ◽  
Vol 13 ◽  
pp. 117955491983392 ◽  
Author(s):  
Joelle El-Amm ◽  
Jeanny B Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Drug Administration ◽  
Advanced Prostate Cancer ◽  
Unmet Need ◽  
Early Data ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Fda Approval ◽  
Variable Potential

Non-metastatic castration-resistant prostate cancer (nmCRPC) is a heterogeneous disease with variable potential in developing into overt metastases. It is an area of increased unmet need in advanced prostate cancer and for which there had been no great treatments until recent US Food and Drug Administration (FDA) approval of 2 novel anti-androgens apalutamide and enzalutamide, which were both approved given benefit in metastasis-free survival. Early data on the use of darolutamide, another novel anti-androgen, are also explored. This review discusses the pivotal trials that led to the approval of apalutamide and enzalutamide in the nmCRPC setting and discusses the key promises and challenges with the use of these agents.

Therapeutic Approach to Castration-resistant Prostate Cancer

2009 ◽  
Vol 05 (01) ◽  
pp. 83
Author(s):  
Fred Saad ◽  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Androgen Deprivation Therapy ◽  
Therapeutic Approach ◽  
Advanced Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Resistant Form ◽  
Near Future ◽  
The Continuum

Androgen deprivation therapy (ADT) has been and continues to be the most common treatment for men with advanced prostate cancer and is now used earlier in the continuum of care for prostate cancer. Unfortunately, the majority of prostate cancer patients on ADT will develop a castration-resistant form of the disease that is responsible for the majority of the morbidity and mortality related to prostate cancer. Given recent advances, there are now therapeutic options available that can reduce the morbidity and improve survival in patients with castrationresistant prostate cancer (CRPC). Research is intensifying in this area and further improvements can be expected in the near future. This review will briefly summarize what is currently available and propose strategies for the management of CRPC.

scholarly journals Assessment of Health-Related Quality of Life in Patients with Advanced Prostate Cancer—Current State and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 147
Author(s):  
Alexander Kretschmer ◽  
Roderick C. N. van den Bergh ◽  
Alberto Martini ◽  
Giancarlo Marra ◽  
Massimo Valerio ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Health Related Quality ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Clinical Scenarios ◽  
Related Quality ◽  
Health Related

With the therapeutic landscape of advanced prostate cancer rapidly evolving and oncological benefits being shown for a plethora of new agents and indications, health-related quality of life (HRQOL)-associated evidence is still subpar. In the current comprehensive review, we discuss the importance of HRQOL for patients with advanced PC (metastatic hormone-sensitive prostate cancer (mHSPC), metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC)), and present the most frequently used tools to evaluate HRQOL in recent randomized trials. Furthermore, we discuss the ease of use of these validated questionnaires for clinicians and try to focus on the suggested appropriate use in clinical practice, as well as potential strategies for improvement of HRQOL evaluation in these clinical scenarios of advanced prostate cancer.

scholarly journals Enzalutamide therapy for advanced prostate cancer: efficacy, resistance and beyond

2019 ◽  
Vol 26 (1) ◽  
pp. R31-R52 ◽  
Author(s):  
Simon Linder ◽  
Henk G van der Poel ◽  
Andries M Bergman ◽  
Wilbert Zwart ◽  
Stefan Prekovic
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Advanced Prostate Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Castration Resistant ◽  
Novel Drugs

The androgen receptor drives the growth of metastatic castration-resistant prostate cancer. This has led to the development of multiple novel drugs targeting this hormone-regulated transcription factor, such as enzalutamide – a potent androgen receptor antagonist. Despite the plethora of possible treatment options, the absolute survival benefit of each treatment separately is limited to a few months. Therefore, current research efforts are directed to determine the optimal sequence of therapies, discover novel drugs effective in metastatic castration-resistant prostate cancer and define patient subpopulations that ultimately benefit from these treatments. Molecular studies provide evidence on which pathways mediate treatment resistance and may lead to improved treatment for metastatic castration-resistant prostate cancer. This review provides, firstly a concise overview of the clinical development, use and effectiveness of enzalutamide in the treatment of advanced prostate cancer, secondly it describes translational research addressing enzalutamide response vs resistance and lastly highlights novel potential treatment strategies in the enzalutamide-resistant setting.

The application of theranostics in different stages of prostate cancer

2021 ◽  
Author(s):  
Omar Alghazo ◽  
Renu Eapen ◽  
Samantha Koschel ◽  
Marcus Cumberbatch ◽  
James Buteau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Advanced Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
New Approach ◽  
Castration Resistant ◽  
Preclinical Trials ◽  
Treat Prostate Cancer ◽  
Castrate Resistant

Despite the remarkable achievements in treating metastatic prostate cancer over the last two decades, castrate-resistant status is still considered the lethal stage of the disease. Theranostics combines a targeting compound (ligand) with a therapeutic radioisotope (radioactive particle) injected into the blood to target the cancer cells. The most studied radioligand is 177Lu-PSMA-617, which targets PSMA, a protein found in prostate cancer cells. This new approach has shown promising results in treating metastatic castration-resistant prostate cancer. Currently, many trials are using PSMA-targeting radioligands in combination with conventional therapies in advanced prostate cancer or even in the earlier stages of the disease. Other preclinical trials are exploring the possibility of using newer ligands or radioisotopes to treat prostate cancer to increase the specificity and efficacy of this treatment.

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