Topic: Metastatic Prostate Cancer

The Importance of Diagnosing and Treating Oligometastatic Prostate Cancer and ADT Usage

The Importance of Diagnosing and Treating Oligometastatic Prostate Cancer and ADT Usage

by | Jun 2024

Dr. Marc Garnick explores the diagnosis and treatment of oligometastatic prostate cancer with the strategic use of androgen deprivation therapy (ADT). Advanced imaging techniques are essential for identifying oligometastatic disease, such as PET scans and advanced MRI. These technologies enhance the precision of detecting small metastatic lesions, facilitating timely and appropriate treatment decisions. By reducing androgen levels that fuel prostate cancer growth, the strategic use of ADT not only helps in controlling the primary tumor but also in managing metastatic lesions, thereby extending the therapeutic window and improving overall survival rates.
Dr. Garnick also addresses the timing and duration of ADT in the context of oligometastatic prostate cancer. He highlights individualized treatment plans based on patient-specific factors, including the extent of disease, patient health status, and response to initial therapies. This personalized approach ensures that patients receive the most effective treatment while minimizing potential side effects associated with prolonged ADT usage.

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Novel Targeted Treatments for Metastatic Disease

Novel Targeted Treatments for Metastatic Disease

by | Nov 2023

Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, discusses the limitations of traditional treatments for metastatic prostate cancer, such as androgen deprivation therapy (ADT) and chemotherapy, which, while effective initially, often lead to resistance and progression. He emphasizes the need for innovative approaches that target specific molecular pathways involved in prostate cancer growth and metastasis.
He highlights several promising targeted therapies currently under investigation. One is the use of PARP inhibitors, such as olaparib and rucaparib, which target cancer cells with defective DNA repair mechanisms, particularly those with BRCA1/2 mutations. Dr. Bryce also discusses the role of androgen receptor (AR) pathway inhibitors, including novel agents like enzalutamide and enzalutamide, which provide more potent and selective inhibition of AR signaling than traditional ADT.
Dr. Bryce switches focuses to radiopharmaceuticals, such as lutetium-177 (Lu-177) PSMA-617, which deliver targeted radiation to prostate-specific membrane antigen (PSMA)-expressing cells. Clinical trials indicate that this approach can effectively reduce tumor burden and improve clinical outcomes in patients with advanced prostate cancer. Additionally, he explores the potential of immunotherapies, including immune checkpoint inhibitors and vaccines, in treating metastatic prostate cancer.

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Identifying Mutations and Optimizing Use of PARP Inhibitors

Identifying Mutations and Optimizing Use of PARP Inhibitors

by | Nov 2023

William K. Oh, MD, highlights the growing significance of precision medicine and the role of genetic profiling in tailoring therapeutic strategies. Dr. Oh begins by outlining the importance of identifying DNA repair gene mutations, particularly BRCA1 and BRCA2, in prostate cancer patients. These mutations, which impair the cell’s ability to repair DNA damage, render the cancer more susceptible to treatments targeting DNA repair mechanisms, such as PARP inhibitors.

Dr. Oh delves into the mechanisms of PARP inhibitors, which function by inhibiting the poly (ADP-ribose) polymerase (PARP) enzyme involved in DNA repair. By blocking this pathway, PARP inhibitors induce synthetic lethality in cancer cells harboring defective DNA repair genes, leading to cell death.

Dr. Oh discusses the importance of patient selection based on genetic profiling and the potential for combining PARP inhibitors with other therapies, such as androgen receptor signaling inhibitors and immune checkpoint inhibitors, to enhance their efficacy. He reviews ongoing clinical trials exploring these combination strategies and their preliminary results.

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Immunotherapy in Metastatic Prostate Cancer

Immunotherapy in Metastatic Prostate Cancer

by | Nov 2023

A. Oliver Sartor, MD, highlights immunotherapy and its goal of harnessing and enhancing the body’s immune system to target and eradicate cancer cells. He emphasizes the distinct mechanisms of immunotherapeutic agents compared to traditional treatments, noting their potential to offer durable responses and improved survival outcomes in specific patient populations.
Dr. Sartor reviews sipuleucel-T, the first FDA-approved immunotherapy for metastatic castrate-resistant prostate cancer (mCRPC), and its ability to extend overall survival, despite minimal impact on disease progression markers like PSA levels. He also addresses the role of immune checkpoint inhibitors, such as pembrolizumab, particularly for mCRPC patients with specific biomarkers like microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). He presents data from recent studies showing promising responses in these subsets of patients, highlighting the importance of genetic profiling in identifying candidates for checkpoint inhibition.
Additionally, Dr. Sartor explores emerging immunotherapeutic approaches, including the use of chimeric antigen receptor (CAR) T-cell therapy and novel vaccines targeting prostate-specific antigens. He discusses the ongoing clinical trials evaluating these innovative treatments and their potential to transform the therapeutic landscape of metastatic prostate cancer.

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Management of mHSPC-Singlets and Doublets and Triplets

Management of mHSPC-Singlets and Doublets and Triplets

by | Nov 2023

Alan H. Bryce, MD, discusses metastatic hormone-sensitive prostate cancer (mHSPC) and the importance of early and effective treatment to improve patient outcomes. While singlet therapy, which typically involves androgen deprivation therapy (ADT) alone, has been the traditional approach, newer evidence supports the use of combination therapies.
Data on doublet therapy, combining ADT with either chemotherapy or a novel hormonal agent such as abiraterone, enzalutamide, or apalutamide, have demonstrated significant improvements in overall survival and progression-free survival compared to ADT alone. Key studies, including the LATITUDE and CHAARTED trials, have established the efficacy of these doublet regimens.
Dr. Bryce also explores adding a second novel agent or chemotherapy to the ADT and initial novel agent combination (triplet therapy). He notes that while triplet therapy may offer further survival advantages, it also carries an increased risk of side effects and requires careful patient selection and management.

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PSA Screening in 2023

PSA Screening in 2023

by | Jun 2023

Gerald L. Andriole, Jr., reviews evidence supporting a more comprehensive family history and biomarkers in screening and treating prostate cancer. Andriole underscores the power of a well-taken family history. He suggests doctors counsel patients on their hereditary risk of prostate cancer, emphasizing the importance of one diagnosed high risk family member, to reduce the rate of mortality.

Describing the Germline Mutations in Metastatic PCa, Andriole recommends all patients with prostate cancer who have certain characteristics be encouraged to speak to their physicians about whether they may need genetic testing for an inherited mutation. When looking in detail at polygenic risk scores (GRS,) knowledge of high GRS decreased mortality rate.

Andriole highlights the Prompt Test, the direct to consumer, poly-genomic test in the US. In comparison, the UK Biobank data compares prevalence and hazard ratio to show the frequency is higher, some predict cancer aggressiveness. He expects to hear a lot about the prompt test in future.

Dr. Andriole recommends identifying patients with clinically significant PCa earlier through a lower PSA cutpoint. He suggests using image guided Micro US or MRI, or a transperineal biopsy to show potentially indicative biomarkers.

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Standard Treatments and Global Perspective

by | Jan 2022

Marc B. Garnick, MD, the Gorman Brothers Professor of Medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center, summarizes recent developments in nomenclature, disease states, and standard treatments for advanced prostate cancer. Using material from a chapter he wrote for ASCO-SEP with David J. Einstein, MD, Assistant Professor of Medicine at Harvard Medical School, Dr. Garnick begins by considering the new language used to describe different states of advanced prostate cancer, including non-metastatic castrate-sensitive prostate cancer (nmCSPC), non-metastatic castrate-resistant prostate cancer (nmCRPC), metastatic castrate-sensitive prostate cancer (mCSPC), and oligometastatic prostate cancer. He then discusses new standards of care for these different states, highlighting recent research indicating the benefits of using darolutamide, enzalutamide, and apalutamide in the nmCRPC setting, and explaining how to appropriately layer and sequence therapies across disease states. He briefly looks at the role of next-generation sequencing in informing the potential benefit of PARP or PD-L1 inhibitors and touches on bone considerations in mCRPC. Dr. Garnick concludes with some comments on the global inequities of prostate cancer treatment, citing data on the significant disparity in mortality-to-incidence rate of prostate cancer in high-income countries compared to low- to middle-income countries.

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Clinical Case Discussion: Metastatic Prostate Cancer and Evidence for More Precision Therapy

Clinical Case Discussion: Metastatic Prostate Cancer and Evidence for More Precision Therapy

by | Dec 2020

A. Edward Yen, MD, Assistant Professor of Medicine in the Hematology and Oncology Section at Baylor College of Medicine, introduces a metastatic prostate cancer case, and through it explores and reviews treatment options. He discusses homologous recombination and the role that it plays in DNA repair pathways, noting that 25% of patients with advanced prostate cancer have deleterious mutations in DNA damage repair genes which lead to an increased risk of prostate cancer and chance of having nodal and/or distant metastases. Dr. Yen then reviews the TRITON2 study on rucaparib in mCRPC patients with homologous recombination deficiency and the PROfound study on olaparib in mCRPC patients with homologous recombination repair alterations, both of which found a far greater response to treatment in the cohorts with the target mutations. Next, Dr. Yen discusses PARP inhibitors and their side effects, such as fatigue, nausea, pulmonary embolism, anemia, and others. Through his exploration of treatment options, Dr. Yen concludes that next-line chemotherapy is the best option for the patient given the visceral progression of their disease.

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