E. David Crawford, MD, Editor-in-Chief at Grand Rounds in Urology, leads a discussion on Androgen Deprivation Therapy (ADT) as the foundation for advanced prostate cancer treatment, supported by Verity Pharmaceuticals. Joining him in this discussion is:
Scott B. Selinger, MD – President of the Advanced Urology Institute, Chair of the Advanced Urology Institute’s Advanced Prostate Cancer committee, and President-Elect of the Large Urology Group Practice Association (LUGPA),
David S. Morris, MD, FACS – President and Director of Advanced Therapeutics Center for Urology Associates
Dr. Crawford begins with a brief overview of the history of ADT and the current options available for hormone-based therapies. Dr. Sellinger notes that with the introduction of more accurate assays, the targeted post-operative levels of testosterone (T) should be less than half of the 50 ng/dl that he had been originally taught. Dr. Morris points out that there is no one-size-fits-all level of testosterone, but agrees that post-op T levels should be as low as possible.
Dr. Crawford presents the group with data from the U.S. Prostate Cancer Conference indicating that just under a third of the experts present believed that the target for post-operative T levels should be 50 ng/dl or lower. Dr. Sellinger points out that 50 ng/dl or lower is the current target held by the FDA, but that active practitioners should be targeting 20 ng/dl or lower, which Dr. Crawford supports with data.
Dr. Crawford shifts the discussion from the ideal post-op T target to the importance of ADT scheduling, pointing out that the current acceptable dose delay is within two weeks. Dr. Crawford asks Dr. Morris for his input on the importance of a consistent administration schedule for interval dosing, and Dr. Morris acknowledges that the available medications provide varying levels of leeway between doses, though keeping the schedule as consistent as realistically possible is always best. Dr. Sellinger chimes in with real-world factors that impact clinicians’ ability to adhere to a strict dosing schedule.
Dr. Sellinger identifies that many of the studies which examined the impact of late dosing used an unrealistic 28-Day month cycle, pointing out that there are no months which consistently have only 28 days. Dr. Crawford follows up this point by presenting a review comparing the impact of late dosing on a 28-Day month against a 30-31-Day month, illustrating a significant spike in the rate of T breakthroughs when dosing was late in the 30-31-Day cycle. The group concludes that monitoring T is the most important factor in evaluating the effectiveness of ADT.
Dr. Crawford then asks the group if failure to monitor T could lead to an erroneous diagnosis of castrate-resistant prostate cancer. Dr. Morris and Dr. Sellinger agree that failure to monitor T could cause a clinician to misdiagnose castrate-resistant prostate cancer, especially when different ADT medications have differing effectiveness and administration procedures.
The group concludes with a discussion of EMBARK results, and the potential impact of newer therapies added to ADT. Dr. Morris focuses on how the EMBARK data suggests better treatment results from intensifying the therapy at first, then de-escalating the therapy once the patient becomes responsive. Dr. Sellinger highlights that many oncologists are still using monotherapy to treat prostate cancer, and expresses optimism at the expanding treatment options for prostate cancer.
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E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology, sits down to talk about how patients and their loved ones can best navigate a prostate cancer diagnosis with David Mobley, MD, FACS, co-author of the book, “Prostate Cancer: Expert Advice for Helping Your Loved One.” They begin by referencing how the idea for the book came about between Dr. Mobley and Contributing Editor for Grand Rounds in Urology, Neil H. Baum, MD, after they saw a similar book intended for the partners of women with breast cancer. They discuss how Dr. Mobley and Dr. Baum, teamed up to address the questions and concerns patients and their partners often have that medical doctors rarely have time to answer in detail.
Dr. Mobley then discusses how Dr. Richard G. Key, MD, a specialist in treating the psychological effects of cancer diagnoses, joined the author team to provide guidance to the man and his partner on how to handle the emotional and psychological symptoms of prostate cancer. They discuss how the inclusion of Dr. Key’s expertise elevated the book by humanizing each case.
Finally, Dr. Crawford and Dr. Mobley discuss how the book relays information in the context of the experience of a couple navigating prostate cancer treatment. The format of each chapter is a vignette of a real prostate cancer patient, followed by an explanation for the questions raised in the vignette, and ending with further questions a man and his partner may have.
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In this discussion, the third in a trilogy on PSMA PET supported by Blue Earth Diagnostics, E. David Crawford, MD, Editor-in-Chief at Grand Rounds in Urology, leads a discussion of the case study of a 60-year-old male presenting with a PSA of 10.5 ng/ml and a Gleason score of 7 after 6 months of ADT and Proton Therapy. He presents this case study to a panel of experts comprised of:
Phillip J. Koo, MD – Division Chief of Diagnostic Imaging and Northwest Region Oncology Physician Executive at the Banner MD Anderson Cancer Center.
Paul L. Nguyen, MD – Director for Radiation Oncology at the Dana-Farber/ Bringham and Women’s Genitourinary Clinical Center; Vice-Chair of Clinical Research in the Department of Radiation Oncology and Professor at Harvard Medical School; Baldwin-Politi Distinguished Chair in Oncology and Associate Director of the Harvard Radiation Oncology Residency Program at Brigham and Women’s Hospital in Boston, Massachusetts.
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 in New Haven, Connecticut.
Dr. Crawford begins by noting that the patient’s conventional imaging results were negative, and asks Dr. Koo whether conventional imaging was indicated in this case. Dr. Koo notes that new RADAR guidelines do not indicate the need for conventional imaging, since the patient’s PSA was greater than 10 ng/ml and his Gleason score was greater than or equal to 7.
Dr. Crawford then asks the panel to weigh in on the patient’s Grade Group, and the panel places the patient in Grade Group 3, Unfavorable Intermediate. When asked about the next steps, the panel unanimously decides on PSMA PET for the patient, with Dr. Petrylak citing the patient’s previous ADT treatment as a major factor in his decision.
Dr. Crawford and the panel then briefly discuss the ambiguity of the term “ADT.” The term “ADT” has been used for years to describe “Androgen Deprivation Therapy,” the use of hormone therapy to treat prostate cancer by depriving the cancer of androgens. However, a number of new agents have been introduced which have effects other than lowering androgens, like Androgen Directed Therapy, potentially rendering the term “ADT” ambiguous. If you would like to share your perspective on ADT terminology, please take a moment to answer this brief survey.
Returning to the case study, Dr. Crawford presents the patient’s follow-up results to the panel, showing a very strong late reaction to the previous therapy in his bladder. After Dr. Nguyen’s recommendation of hyperbaric oxygen (HBO), Dr. Crawford reveals that the patient was treated with HBO for 4 weeks.
After 3 months, the patient presented with a PSA of 8.32 ng/ml. Dr. Kim, with support from the panel, recommends PSMA PET, and points out the limitations of the MRI and CT scans that had been previously done on the patient. Dr. Crawford then presented the results from the patient’s biopsies, which appeared to indicate benign tissue.
Finally, Dr. Crawford reveals that he was able to run a PSMA PET scan on the patient. The scan revealed multiple foci of increased uptake within the prostate gland which had been missed in the biopsies. The panel concludes with a diagnosis of metastatic cancer and a recommendation for a course of ADT and 3rd-generation anti-androgens as treatment.
This is the third talk in a trilogy of discussions on PSMA PET supported by Blue Earth Diagnostics. For the first installment, click here. For the second installment, click here.
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Editor-in-Chief of Grand Rounds in Urology, E. David Crawford, MD, and Stephen J. Freedland, MD, discuss highlights on prostate cancer research from the recent European Society for Medical Oncology (ESMO) meeting in Madrid, Spain. At that meeting, Dr. Freedland presented on the EMBARK trial, a Phase 3, randomized study of enzalutamide or placebo-plus-leuprolide acetate and enzalutamide monotherapy in high-risk, biochemically recurrent prostate cancer. With regard to how these treatments affect quality of life, he explains there is no evidence of a difference in quality of life among them and the major takeaway is that patients do not have to sacrifice quality of life to get cancer benefits.
Dr. Freedland then addresses the PSMAfore clinical trial of patients who had failed when treated with a non-hormonal agent, had a positive prostate-specific membrane antigen (PSMA) scan, and were eligible for PSMA lutetium therapy (Pluvicto). The patients were randomized for Pluvicto or other androgen receptor (AR)-targeted agents. The primary outcome was radiographic progression-free survival.
Dr. Freedland characterizes the study as very positive and clinically relevant with over a 57 percent delay in progression. He explains that afterward, 84 percent of patients who were receiving the other AR-targeted agents ended up crossing over to receive the Pluvicto. Dr. Freedland points out that overall survival between the trial arms showed no difference and asserts that between these results and those shown during the VISION trial, establishing Pluvicto as a tool practitioners should be using for these eligible patients.
Drs. Crawford and Freedland conclude that these are compelling research developments, and Dr. Freedland asserts that these were among the biggest take-home messages from the ESMO meeting.
