Prostate Cancer Management PDF

Molecular Medicine Advancements in Advanced Prostate Cancer Dr Temba Mudariki  Learning Outcomes Understand the epidemiology and disparities in prostate cancer, focusing on the impact on Black men. Recognize the updates and ame...

Molecular Medicine Advancements in Advanced Prostate Cancer Dr Temba Mudariki  Learning Outcomes Understand the epidemiology and disparities in prostate cancer, focusing on the impact on Black men. Recognize the updates and amendments made in the 2023 AUA/SUO Guideline for the management of advanced prostate cancer. Evaluate the significance of advanced PET imaging and theranostics in the management of prostate cancer. Discuss the evolving landscape of systemic therapies and biomarkers in the treatment of advanced prostate cancer. Analyse the unmet needs and future directions in the management of advanced prostate cancer, focusing on personalized care and therapeutic advancements.  OVERVIEW  Introduction  Genetic Factors  Epidemiology and Disparities  Advanced Prostate Cancer Management Updates  Therapeutic Decision-making and Systemic Therapies  Unmet Needs and Future Directions  Conclusion and Future Perspectives  Genetic Factors in Prostate Cancer 1. Protein Regulating Cell Growth: Gene: PTEN (Phosphatase and Tensin Homolog) Role: Regulates cell growth and is frequently overexpressed in prostate cancer 2. Frequently Observed Gene Fusion: Gene Fusion: TMPRSS2-ERG Fusion Role: Linked to the development of a subset of prostate tumours, commonly observed in prostate cancer  Genetic Factors in Prostate Cancer 3. Gene Mutation Associated with Hereditary Prostate Cancer: Gene: BRCA1 and BRCA2 Role: Mutation in these genes is associated with hereditary prostate cancer and an increased risk of developing aggressive forms of the disease 4. Therapeutic Target Protein: Protein: Androgen Receptor (AR) Role: Overexpression of AR is a therapeutic target for prostate cancer treatment and is associated with a subset of advanced prostate tumours  Introduction and Background Overview of Prostate Cancer – Significant public health concern Prevalence and Mortality of Prostate Cancer  Prostate cancer is one of the most prevalent cancers affecting men globally  Ranks among the most common malignancies diagnosed in men-USA  Second leading cause of cancer-related deaths in this population  Black men – Disparity more pronounced  Introduction and Background 2023 AUA/SUO Guideline Amendment Updated evidence-based recommendations for the management of advanced prostate cancer Encompassing biochemical recurrence without metastatic disease Metastatic hormone-sensitive prostate cancer (mHSPC) Non-metastatic castration-resistant prostate cancer (nmCRPC) Metastatic castration-resistant prostate cancer (mCRPC) Evolving landscape of treatment options Critical resource for healthcare professionals  Epidemiology and Disparities Prostate cancer epidemiology reveals significant trends -incidence and mortality rates Disparities affecting Black men Incidence and Mortality Rates Most prevalent cancers among men worldwide The most common solid organ malignancy –USA Leading cause of cancer-related deaths in men Black men experiencing a higher risk compared to other racial and ethnic groups. Mortality rates also reflect disparities - Black men facing a disproportionately higher mortality rate  Epidemiology and Disparities Disparities Affecting Black Men Face a higher incidence of prostate cancer Mortality rate among Black men is approximately double Ongoing research into screening practices Access to care Treatment considerations for Black men Ongoing Investigations and Considerations Address the disparities affecting Black men Screening - aiming to enhance early detection and intervention Advanced Prostate Cancer Management Updates American Urological Association (AUA) and Society of Urologic Oncology (SUO) guidelines Introduced significant changes in the management of various stages of advanced prostate cancer Biochemical recurrence without metastatic disease Metastatic hormone-sensitive prostate cancer (mHSPC) Non-metastatic castration-resistant prostate cancer (nmCRPC) metastatic castration-resistant prostate cancer (mCRPC) Biochemical Recurrence without Metastatic Disease Revised guidelines provide updated recommendations for patients  Experiencing rising prostate-specific antigen (PSA) levels after the failure of local therapy  Not presenting with demonstrable metastatic disease through conventional imaging. *Treatment Options- Observation or Clinical trial enrolment *Systemic Treatments - Impact of treatment-related adverse events and the patient's quality of life. The introduction of advanced imaging modalities -PSMA PET imaging  Enhanced sensitivity and specificity in the detection of metastatic disease  Updates have influenced the approach to managing patients with rising PSA levels post-local therapy. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Prognosis assessment and treatment recommendations for patients diagnosed with mHSPC. Extent of metastatic disease in newly diagnosed mHSPC patients Role of PSMA PET imaging in this assessment Utilization of androgen deprivation therapy (ADT) in combination with androgen pathway-directed therapy Chemotherapy, based on recent clinical trials and evidence. Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC) Role of PSMA PET Imaging  PSMA PET imaging for monitoring the disease status of men with nmCRPC  Enhanced sensitivity and accuracy in detecting potential metastatic lesions  More precise disease monitoring and treatment planning *Impact of PSADT  PSA doubling time (PSADT) in assessing disease progression  Identifying high-risk patients Recommendations for Imaging Intervals  Regular imaging evaluations for men with nmCRPC  The integration of PSMA PET imaging -disease monitoring and the potential for early detection of metastatic progression Metastatic Castration-Resistant Prostate Cancer (mCRPC) The updated guidelines emphasize the necessity for annual imaging in mCRPC patients without PSA progression or new symptoms. Additionally, they introduce the potential use of 177Lu-PSMA-617 in the context of progressive mCRPC, based on positive PSMA PET imaging study, and its impact on patient outcomes. Significance of Advanced PET Imaging, such as PSMA PET Prostate-Specific Membrane Antigen Positron Emission Tomography  Advanced molecular imaging technique used in the evaluation of prostate cancer  Utilizes positron emission tomography (PET) in combination with a radiotracer  Targets the prostate-specific membrane antigen (PSMA)  It has Influenced the diagnosis and management of advanced prostate cancer  Enhanced sensitivity and specificity in detecting metastatic sites  Impacting treatment planning by altering clinical decision-making The guidelines highlight the role of PSMA PET imaging  Identifying metastatic sites not previously detected with conventional imaging  Potential implications of these findings in patient outcomes and therapeutic decisions  Therapeutic Decision-making and Systemic Therapies in Advanced Prostate Cancer Metastatic hormone-sensitive prostate cancer (mHSPC) Evidence-based recommendations for Metastatic castration-resistant prostate cancer (mCRPC) therapeutic decision-making Recommendations encompass  Androgen receptor pathway inhibitors  Chemotherapy  Novel agents such as 177Lu-PSMA-617 Androgen Receptor Therapeutic Decision-making in mHSPC and mCRPC Evidence-based guidelines provide clear recommendations  mHSPC, the guidelines emphasize the use of androgen deprivation therapy (ADT) in combination with either androgen pathway-directed therapy abiraterone acetate plus prednisone, apalutamide, or enzalutamide  Chemotherapy (commonly docetaxel). Evidence supports the significant extension of overall survival and progression-free survival in mHSPC patients In mCRPC - ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide  Additionally, the novel agent 177Lu-PSMA-617 - particularly those with progressive disease following prior treatments The inclusion of 177Lu-PSMA-617 in the guidelines reflects the evolving landscape of therapeutic options for advanced prostate cancer. Role of Biomarkers and Other Systemic Therapies Identifying DNA repair deficiencies, microsatellite instability (MSI) status, and tumour mutational burden has gained prominence Inform prognosis and familial cancer risk while also guiding potential targeted therapies Guidelines underscore the potential importance of germline and somatic tumour testing  Predicting responses to PARP inhibitors such as olaparib, rucaparib, and niraparib PARP inhibitors target DNA replication machinery  Promising outcomes in tumours with deficiencies in homologous recombination repair, such as those with BRCA1 or BRCA2 mutations. Guidelines explore the potential of immunotherapies in the management of advanced prostate cancer.  These treatments have generally shown less efficacy in prostate cancer compared to other malignancies Due to the relatively low tumour mutational burden of most prostate cancers Unmet Needs and Future Directions in Prostate Cancer Management Management of prostate cancer continues to face various unmet needs  Disparities in outcomes, the demand for personalized care, and the exploration of the optimal sequencing of therapies Disparities in Outcomes and Personalized Care  Subpopulations such as Black patients  Understanding the societal and biological factors contributing to these disparities Ensure equitable access to high-quality care and improved outcomes Demand for personalized care  Predictive markers for treatment selection based on tumour and host biology Personalized care can enable tailored treatment approaches  Individual patient characteristics Ultimately improving patient outcomes and treatment efficacy Unmet Needs and Future Directions in Prostate Cancer Management Optimal Sequencing of Therapies - establishing clear guidelines for the sequencing of these therapies is imperative Understanding the most effective sequence of treatments can lead to improved treatment outcomes Reduced side effects Enhanced quality of life for patients with advanced prostate cancer Unmet Needs and Future Directions in Prostate Cancer Management Theranostics, an emerging field that integrates diagnostic and therapeutic strategies  Prostate-specific membrane antigen (PSMA) targeted therapy Offers the promise of precision-guided therapy and the potential for improved treatment outcomes PSMA PET  Play a pivotal role in the early detection of metastatic sites  Treatment planning  Improved patient outcomes. Application of metastasis-directed therapy (MDT)  Radiation, surgery, or ablative technologies Represents a burgeoning area of interest in the management of advanced prostate cancer  Summary Conclusion and Future Perspectives Advancements in Advanced Prostate Cancer Management Emphasis on Future Research and High-Quality Clinical Trials End of Session