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Emerging Role of PSMA Imaging

Emerging Role of PSMA Imaging

Posted by | Dec 2021

Steven P. Rowe, MD, PhD, Associate Professor of Radiology and Radiological Science at Johns Hopkins University in Baltimore, Maryland, discusses the emerging role of prostate-specific membrane antigen (PSMA) imaging. He defines PSMA as a transmembrane carboxypeptidase highly expressed in prostate cancer cells. This expression has been observed in over 95 percent of prostate cancer tumors, with a direct correlation between expression levels and tumor aggressiveness. Due to this, Dr. Rowe asserts that PSMA is an excellent target for molecular imaging of prostate cancer. Dr. Rowe displays a PSMA structure and activity diagram and explains that PSMA positron emission tomography (PET) has moderate sensitivity and very high specificity for pre-operative nodal staging, high detection efficiency for sites of biochemical recurrence (BCR), and can effectively guide focal therapy for oligometastases and is effective in selecting patients for endoradiotherapy. He then discusses each of these in more detail, highlighting data from a study that evaluated the diagnostic performance of PSMA-targeted 18F-DCFPyL PET/computerized tomography in the preoperative staging of men at high risk for harboring metastatic prostate cancer. Dr. Rowe shows data on PSMA-based therapy and points out that for patients with more widespread metastatic disease, treatment may include PSMA inhibitors such as lutetium-177. Dr. Rowe expects that lutetium-based PSMA therapy will be approved by the FDA and become part of the standard of care for patients with widespread metastatic disease. Dr. Rowe then outlines lingering questions about PSMA PET imaging, including how prognostic findings may look for different patient populations, how doctors should follow response to therapy given that decreasing androgen signaling leads to increase in PSMA expression, and what role artificial intelligence (AI) is going to play. Dr. Rowe illustrates data from the Observation vs. Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) trial results for oligometastatic disease, pointing out that patients who had all lesions visible on a PSMA scan treated had better outcomes than those who only had a subset of their PSMA-positive lesions treated. Dr. Rowe predicts that in the near term, AI will provide lesion classification, whole-body tumor burden assessments, and prognostication and decision-making based on scan findings and clinical data. In conclusion, Dr. Rowe explains that, based on existing studies, there are already multiple indications for diagnostic PSMA-based imaging, with the caveat that researchers are just starting to understand PSMA-targeted PET findings as imaging biomarkers, and currently there are still questions about the interface of PSMA PET with AI.

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The Latest Dope on Medical Marijuana

Posted by | Dec 2021

Grand Rounds in Urology Contributing Editor Neil H. Baum, MD, Professor of Urology at Tulane Medical School, discusses the latest research on medical marijuana, noting that it is increasingly popular with patients and that almost all physicians, including urologists, should expect questions about it. He gives a brief history of cannabis, from its use as an herbal medicine in 500 BCE, to its criminalization in 1937 and, eventually, to its legalization for both medical and recreational uses over the last few decades. Dr. Baum then defines several terms, explaining the difference between cannabidiol (CBD), which is not psychoactive and has anti-inflammatory properties, and tetrahydrocannabinol (THC), which is psychoactive and increases appetite. He lists the conditions marijuana is purportedly beneficial for including chronic pain, alcohol and drug addiction, insomnia, depression, post-traumatic stress disorder, social anxiety, nausea and vomiting associated with chemotherapy, gastrointestinal disorders, multiple sclerosis, and certain forms of epilepsy. Dr. Baum notes that while there is some evidence supporting marijuana’s benefits for several of these conditions, randomized controlled trials are needed to substantiate many claims.

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Updates in Treatment of Renal Cell Carcinoma

Posted by | Dec 2021

Robert R. Dreicer, MD, MS, MACP, FASCO, Associate Director for Clinical Research and the Deputy Director of the University of Virginia Cancer Center, discusses the challenges in picking an optimal front-line regimen for the treatment of renal cell carcinoma and the impact of adjuvant immuno-oncology (IO) therapy. He cites data from four trials (CheckMate 214, Keynote-426, CheckMate 9ER, and CLEAR) before outlining the challenges in choosing an optimal front-line regimen. Dr. Dreicer points out that there is no comparative data currently available before explaining that tyrosine kinase inhibitors (TKIs, formerly the standard of care for kidney cancers) are toxic, challenging drugs that impact a patient’s quality of life. Dr. Dreicer outlines the therapies available today, including ipilimumab plus nivolumab (IPI-NIVO) which he characterizes as challenging for the first couple of months but well-tolerated in the last ~20 months during which patients undergo a maintenance regimen of nivolumab. He points out that treatment can be stopped after two years for patients that respond well. Dr. Dreicer asserts there is no equivalent conclusion with a TKI checkpoint. Dr. Dreicer then turns his discussion to the KEYNOTE-564 study on pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for patients with renal cell carcinoma. He outlines the study design and eligibility criteria before displaying the disease-free survival (DFS) data showing the adjuvant therapy resulted in a 32 percent reduction in recurrence or death. Dr. Dreicer argues that for patients who can access an IO-based regimen, IPI-NIVO should be the standard of care, advising that while there is not one “right answer” to the optimal treatment question, practitioners ought to use one regimen, figure out what it’s toxicities are, and learn how to use it well. Dr. Dreicer then outlines questions that will emerge if an adjuvant checkpoint inhibitor becomes a standard of care, citing disruption to the front-line paradigm, the role of subsequent IO therapy, progression while on adjuvant therapy, and progression following adjuvant therapy. Dr. Dreicer emphasizes the need for other trials and the need to develop therapeutics that work in immune-checkpoint resistance.

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Role of ADT with Radiation

Role of ADT with Radiation

Posted by | Dec 2021

Steven E. Finkelstein, MD, FACRO, a radiation oncologist with Florida Cancer Affiliates in Panama City, Florida, discusses the role of androgen deprivation therapy (ADT) with radiation therapy (RT) in patients with prostate cancer. Dr. Finkelstein first discusses the definitive setting, explaining optimal durations for the addition of ADT to RT under various circumstances. For example, when local control with RT alone is good, ADT is never given; when the risk of local failure is high, ADT is given for 3-6 months as a radiation sensitizer; and when the risk of distant disease is high, ADT treatment is given for 2-3 years. Dr. Finkelstein goes on to illustrate data that show ADT does not improve survival in men receiving RT for low-risk disease, short-term ADT improves survival in men receiving RT for intermediate-risk disease, and ADT was effective in improving survival for patients with “modern” high- and intermediate-risk disease. Dr. Finkelstein discusses dose escalation in RT and cites an ongoing study examining 1520 patients who received either 79.2 Gy alone or 79.2 Gy plus 6 months of ADT, with the primary endpoint being overall survival (OS), asserting that the study will be seminal once the results have been published. He then reviews the current summary recommendations in the definitive setting: for low-risk (NCCN definition) and low-intermediate-risk patients, the recommendation is surveillance, brachytherapy (BT), or external beam radiation therapy (EBRT) with no recommendation for ADT; for high-intermediate risk patients, the recommendation is EBRT +/- BT with 4-6 months of ADT (GnRH agonist); and for high-risk (NCCN definition) patients, the recommendation is EBRT +/- BT with 24 months of ADT(GnRH agonist). Dr. Finkelstein then introduces Kevin D. Healey, a research intern and medical student level two, who delivers the second part of the presentation, focusing on the salvage setting. Mr. Healey presents research from the GETUG-AFU 16 trial, examining short-term ADT combined with RT as salvage treatment after radical prostatectomy for prostate cancer: a 112-month follow-up of a phase 3, randomized trial. He concludes that salvage RT combined with short-term ADT significantly reduced the risk of biochemical or clinical progression and death compared with salvage RT alone. Further, the results of the trial confirm the efficacy of ADT plus RT as salvage treatment in patients with increasing PSA concentration after radical prostatectomy for prostate cancer. Dr. Finkelstein then concludes the presentation with the current summary recommendations for the salvage setting, including adding a 6-month course of ADT (LHRHa) to salvage RT in men with no or minimal comorbidity, given the near halving of progression and the possible reduction in mortality due to prostate cancer.

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