Alan H. Bryce Archives

Putting Germline Testing into Context – A Primer and Current Knowledge

Posted by Alan H. Bryce, MD | Jul 2024

Alan H. Bryce, MD, outlines the current state and potential future directions of germline testing in prostate cancer detection and treatment. He begins with a review of the currently known genetic mutations associated with prostate cancer.

Dr. Bryce then reviews the NCCN criteria for germline genetic testing for patients with new or previously diagnosed prostate cancer. He presents data that supports the idea that current testing guidelines are not effective in identifying the presence of known pathogenic germline variants (PVGs) in patients with prostate cancer.

Dr. Bryce then examines the relationship between disease progression and the presence of PVGs. He presents data illustrating the correlation of certain PVGs and the likelihood of disease progression.

Dr. Bryce concludes by highlighting the lack of available data for different racial groups. He notes that most of the available PGV data is based on the testing and surveillance of Caucasian males, leaving all other racial groups underrepresented in the data.

Perspectives in mCRPC in 2024

Posted by Alan H. Bryce, MD | May 2024

Alan H. Bryce, MD, reviews current research, perspectives and practices in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Dr. Bryce begins with an overview of current treatment options and patterns of care and addresses the National Comprehensive Cancer Network (NCCN) Guidelines Version 4.2023 for prostate cancer.

Dr. Bryce asserts that in light of few patients receiving treatments beyond first-line, a key operational principle should be to use the best drugs as early as possible. He explains that the management of mCRPC has become increasingly complex as new treatment paradigms have developed and new drugs have been approved. He recommends thinking about classes of drugs and considering how switching or combining classes can have advantages from the perspective of disease evolution.

Dr. Bryce concludes with a brief overview of recent phase-three trial results including PSMAfore, SPLASH, and CONTACT-2. He acknowledges that after several years of continuous success, the development of new classes of drugs for prostate cancer has hit a lull but he asserts the pipeline is still full and since there is not yet a cure for prostate cancer, trials must continue.

Novel Targeted Treatments for Metastatic Disease

Posted by Alan H. Bryce, MD | 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.

Management of mHSPC-Singlets and Doublets and Triplets

Posted by Alan H. Bryce, MD | 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.

Radioligand Therapy in Prostate Cancer

Posted by Geoffrey B. Johnson, MD, PhD | Jun 2023

Geoffrey B. Johnson, MD, PhD, Chair of the Division of Nuclear Medicine at the Mayo Clinic in Rochester, MN, discusses radioligand therapy in prostate cancer. Dr. Johnson briefly reviews the specific activity of this therapy, with a focus on Lutetium-177-PSMA-617.
Dr. Johnson highlights the benefits and tolerable side-effects of Lutetium-177-PSMA-617, and mentions the therapy is approved for patients with metastatic castrate-resistant prostate cancer who have been previously treated with androgen receptor pathway inhibition and taxane-based therapy.

The presentation further explores the process of patient selection for PSMA imaging, with the requirement of at least one lesion that shows higher PSMA expression than the liver. Dr. Johnson showcases post-therapy imaging examples, and discusses the potential of advanced scanning techniques, such as CZT-based scanners, which offer higher sensitivity and faster scans for accurate tracking of therapy response.

Dr. Johnson emphasizes the promising future of radionuclide therapy. He mentions the potential combinations of PSMA therapy with hormonal therapy, chemotherapy, immunotherapy, and external radiation. Additionally, he mentions ongoing trials exploring the use of alpha and beta emitters and the incorporation of different targets.