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2024

PET Tumor Board: Case #5

In this discussion, E. David Crawford, MD, Jack A. Vickers Director of Prostate Research and Professor of Urology at the University of California, San Diego, leads a discussion of the case study of a healthy 69-year-old male with a history of multiple BPH treatments presenting with Gleason Grade 2 prostate cancer. He presents this case study to a panel of experts comprised of:

Wayne G. Brisbane, MD – Assistant Professor of Urology at the University of California, Los Angeles.
Phillip J. Koo, MD – Division Chief of Diagnostic Imaging and Northwest Region Oncology Physician Executive at the Banner MD Anderson Cancer Center.
Daniel P. Petrylak, MD – Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center.

After reviewing the patient’s treatment history, Dr. Crawford informs the panel that the patient initially presented with a PSA of 4.55 ng/ml, his 12 core biopsies were negative after 6 months of treatment, and he was placed on active surveillance post-biopsies. However, the patient returned one year after initial presentation with a PSA of 8.5 ng/ml. Dr. Crawford asks the panel to weigh in on next steps.

Dr. Petrylak recommends pursuing active surveillance based on the patient’s 2.1% Decipher score and the patient’s preference of preserving his quality of life. Dr. Koo suggests using an mpMRI to resolve the discordance between the PSA level and the negative biopsies.

Dr. Crawford shows the results from the patient’s POSLUMA scan which showed focal uptake in the right base of the prostate. Dr. Koo acknowledges that the scan results are promising, but he reminds the panel to be cautious about the sensitivity of PSMA PET before definitive therapy.

Dr. Crawford reveals that the patient had an mpMRI and 12 core biopsies in addition to the POSLUMA scan, all of which confirmed the presence of prostate cancer in the right base. The panel recommends focal therapy as a next step, and discusses the available options for focal therapy.
This is the fifth in a series of discussions on PSMA PET supported by Blue Earth Diagnostics. For the first installment, click here. For the second installment, click here. For the third installment, click here. For the fourth installment, click here.

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Mechanisms and Management of Recurrence

Samir S. Taneja, MD, examines the mechanisms underlying focal therapy failure and best practices in managing prostate cancer recurrence. He begins by defining “failure” in the context of focal therapy, noting that progression-free survival may be a better benchmark for determining the success of focal therapy, rather than recurrence-free survival.

Dr. Taneja then addresses the most common expressions of cancer recurrence post-focal therapy: metastatic recurrence, multifocal recurrence, and recurrence of the treated tumor. He provides real-world examples of treatment failure for each type of recurrence, illustrates the underlying mechanisms, and suggests practical techniques and tools for preventing or managing focal therapy failure.

Dr. Taneja concludes by providing guidance on when focal therapy is no longer appropriate. He advises that re-ablation is not appropriate for high-risk prostate cancer patients or in patients with extraprostatic recurrence.

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Pelvic Lymphadenectomy and Radical Cystectomy – Current Standard of Care

Seth P. Lerner, MD, FACS, reviews the current standard of care for pelvic lymphadenectomy and radical cystectomy in treating bladder cancer. He begins by focusing on the technique and extent of pelvic lymphadenectomy performed in conjunction with radical cystectomy. He illustrates that an extended approach can improve oncologic outcomes, including better cancer-specific survival and overall survival rates, by ensuring more comprehensive removal of potential metastatic sites.

Dr. Lerner then addresses advancements in surgical techniques, including robotic-assisted surgery for radical cystectomy and lymphadenectomy. He discusses the potential benefits of robotic surgery while also considering the challenges and learning curve associated with these technologies.

Dr. Lerner concludes with a review of postoperative management and follow-up care and discusses future directions and ongoing research. He emphasizes the need for continued investigation into optimizing surgical techniques, enhancing patient outcomes, and integrating new therapeutic modalities with surgery.

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How to Use Natural Ligands to Kill Tumor Stem Cells

Stephen B. Howell, MD, explores the possibility of using Cancer Stem Cell-Targeted Therapy to fight cancerous tumors and prevent recurrence. He begins with a review of the role of LGR receptors and RSPO ligands in active stem cells.

Dr. Howell then presents data from a trial demonstrating how a particular drug, FcF2-MMAE, can target cancerous tumor cells through a particular LGR receptor. He provides data on FcF2-MMAE’s promising pharmacokinetic and pharmaceutical properties

Dr. Howell concludes by stating that the drug needs to be studied outside of an academic research environment. While most of the academic research has been done on the responsiveness of tumor stem cells in ovarian cancer, he anticipates that the FcF2-MMAE framework may have applications for prostate cancer tumors.

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Putting Germline Testing into Context – A Primer and Current Knowledge

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.

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