International Prostate Cancer Update

Next Generation Imaging for Prostate Cancer

Phillip J. Koo, MD, Division Chief of Diagnostic Imaging and Northwest Region Oncology Physician Executive at the Banner MD Anderson Cancer Center in Phoenix, Arizona, gives an overview of the current state of next generation imaging (NGI) for prostate cancer and how it compares to conventional imaging, i.e., bone scans and CT scans. He begins by noting that while there are strengths to conventional imaging and the NCCN clinical guidelines still recommend its use, it misses a lot of cancer, especially in patients with low PSA or biochemical recurrence (BCR). Dr. Koo suggests that NGI is to conventional imaging as a high-definition television is to a conventional one: both show a picture, but one shows a clearer one. He briefly looks at how NGI for prostate cancer works, explaining that NGI takes advantage of unique biological aspects of prostate cancer carcinogenesis and that increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabeled analogs of choline, acetate, glucose, amino acids, and nucleotides. Dr. Koo then goes over the different approved NGI PET/CT options, including 11C-choline, 18F-fluciclovine, 68Ga-PSMA-11, and PyLARIFY PSMA. He particularly focuses on the 2 PSMA ligands, since data indicates that PSMA PET/CT performs better than anything used in the past, detecting more cancer at lower PSA levels than other techniques and in places where prostate cancer has rarely been seen before. Dr. Koo notes that PSMA is not infallible though, highlighting a study showing that while 68Ga-PSMA-11 generally has better detection rates than fluciclovine, fluciclovine has a higher detection rate in the prostate bed, suggesting that each radiopharmaceutical has its own strengths and weaknesses. He concludes with a summary of when and how clinicians should use NGI, emphasizing that NGI is here to stay and the field of urologic oncology should be prepared for rapid change.

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Management of Biochemical Recurrence

Peter R. Carroll, MD, MPH, Professor of Prostate Cancer and Urology at the University of California, San Francisco, discusses advancements in knowledge of biochemical recurrence post radical prostatectomy. He begins with an overview of the evolution of radical prostatectomy (RP), highlighting that it has become a treatment option designated for high-risk patients, more multimodal, and more enhanced by biomarker and imaging technology. Dr. Carroll shows data from the CAPTURE trial suggesting that when looking at 18-year cause-specific mortality, RP has a benefit to high risk patients over low risk patients. He reviews data from a Martini-Klinik trial on PSA after RP predicting cancer death that found 75.5% survival in RP patients with detectable PSA vs 96.2% in patients with undetectable PSA. Dr. Carroll also discusses data from a trial he took part in managing which supports the data from Martini-Klinik. He then overviews data from the RAVES, GETUG – AFU 17, and RADICALS RT trials that all compare salvage therapy against adjuvant and found no real difference in outcomes with differences of 3% at most. Dr. Carroll reviews data showing that early adjuvant therapy has a survival benefit for high-risk patients with Gleason scores of 8-10 and UCSF data showing 33% salvage PSA recurrence-free survival post salvage radiation at 10 years. He discusses how empirically based treatment strategies don’t take into account the treatment niches shown by the data he has reviewed and recommends that exact treatment strategies are utilized on a patient by patient basis and that a measured approach to managing biochemical recurrence is utilized.

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Update on New Approaches Combining Brachytherapy with Immunotherapy

Steven E. Finkelstein, MD, FACRO, a radiation oncologist with Florida Cancer Affiliates in Panama City, Florida, discusses the process of combining brachytherapy with immunotherapy, highlighting the need for better applicators. He begins the presentation by describing radical prostatectomy, external beam radiation (EBRT), cryotherapy, and brachytherapy, and then reviews data on each of their relapse-free survival results. A trial found that when comparing EBRT with surgery against EBRT with brachytherapy, treatment with EBRT in combination with brachytherapy has a higher rate of PSA progression-free survival, and including ADT increases the rate even more. Dr. Finkelstein then considers the “cogwheels of cancer practice,” i.e., the idea that the combination of guidelines, management, bias, patient preference, marketing, reimbursement, payer, and task force systems sometimes takes more precedence in treatment choice than data. He goes on to describe brachytherapy in detail, noting that it uses precisely-delivered radiation sources to treat cancer within patients through small applicators that are unable to apply additional therapeutic agents. He cites this shortcoming as support for a need for applicators for additional therapeutic approaches. Dr. Finkelstein continues with a detailed overview of radiation-driven immunotherapy. He discusses a study showing that radiation can induce unique cellular expression of MHC Class I adhesion molecules, costimulatory molecules, heat shock proteins, inflammatory mediators, immunomodulatory cytokines, and death receptors. He concludes with a discussion of “Immuno-Site,” an applicator designed to provide simple, effective, and isolated localized radiation therapy, including brachytherapy and immunotherapy simultaneously.

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Diet Only and Prostate Cancer

Mark A. Moyad, MD, MPH, Jenkins/Pokempner Director of Preventive/Complementary and Alternative Medicine (CAM) in the University of Michigan Department of Urology, reviews several trials showing the impact of dieting to lose weight on cancer and cancer recurrence, focusing particularly on prostate cancer. He begins with a discussion of the WINS and WHEL trials on dietary changes and breast cancer which, together, found that improving the quality of a diet does not appear to have a profound impact on cancer or recurrence, but that while dieting with a focus on weight loss reduces recurrence rates and establishes a number needed to treat (NNT) of 38. Dr. Moyad continues with preliminary data from the Success-C trial, a study with the goal of using caloric reduction and exercise to reduce weight and is showing that those who adhere to the lifestyle changes have significantly improved rates of disease-free survival. He then looks at the POUNDS LOST trial, whose results suggest that, regardless of the weight-loss process, if weight loss occurs then health benefits can be reached. Dr. Moyad also discusses the CALERIE and MEAL trials. The former study had patients cut back calories by 13% on average and showed that slow methodical weight-loss creates heart-healthy metabolic and numeric changes. The latter had active surveillance participants significantly increase their vegetable intake but has not currently found any remarkable differences between the control and intervention groups. He also discusses the latest impressive vegan randomized study, which demonstrated dramatic weight loss of 14 lbs over 16 weeks utilizing a practically unrecognized caloric reduction strategy. He summarizes the results of over 85 studies on excess alcohol and adipose tissue which support the idea that both are carcinogens and are shown to reduce the efficacy of some drugs. Dr. Moyad also observes that data on lycopene shows that increased fruit and vegetable intake is supportive of overall heart health, how recent research shows no clear cause and effect link between cancer and vitamin D or omega 3s, and how the MANSMED trial shows the benefit of using metformin in addition to standard-of-care therapy. He concludes by observing that heart-healthy calorie restriction programs that encourage adherence, happiness, and healthy outcomes are good for managing prostate cancer, and by briefly discussing the potential of semaglutide injections to help some patients lose weight.

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Surveillance After Image-Targeted Focal Therapy

Thomas J. Polascik, MD, FACS, Professor of Surgery at Duke University and Director of Surgical Technology at the Duke Prostate and Urological Cancer Center, discusses the process of active surveillance and retreatment after image-targeted focal therapy (FT). He begins by describing cancer control and how it may fail. Dr. Polascik then defines intermediate to long-term treatment success as eradication of all aggressive or clinically significant disease in the treated zone, and treatment failure as a significant volume of .2 cc or greater of GS 3+4 in the treated zone and development of any foci of clinically significant cancer requiring further therapy. He cites several studies as contributing to the conclusion that PSA alone is insufficient in defining oncological success, and that a targeted and systematic biopsy should be done 6 to 12 months post-treatment based on rising PSA or suspicious mpMRI lesions. Dr. Polascik then reviews a study outlining guidelines for post-treatment FT for localized prostate cancer in clinical practice. He outlines FT failure through the categories of ablation, targeting, and selection failure, which respectively consist of leaving a tumor in the ablation area, energy not being correctly applied to the tumor, and a patient being inappropriately selected for FT. Dr. Polascik then discusses repeat FT, stating that it is recommended when the reasons for the initial failure can be identified and corrected. He cites Donaldson et al. as showing that FT retreatment rates below 20% are clinically acceptable, any subsequent whole gland therapy reflects a failure of focal therapy, and that a retreatment rate of below 10% with whole gland therapy is clinically acceptable. He concludes by stating that functional outcomes will be clear at between 12 and 18 months post-treatment and by recommending that a post-ablation targeted biopsy of the ablation zone and any new lesions be done between 6 and 12 months post-treatment and possibly 5 years post-treatment, and that PSA density be used for surveillance.

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