Video

Update on New Approaches Combining Brachytherapy with Immunotherapy

Posted by | Aug 2021

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

Posted by | Aug 2021

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

Posted by | Aug 2021

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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The Microbiome as a Mediator of Prostate Carcinogenesis

The Microbiome as a Mediator of Prostate Carcinogenesis

Posted by | Aug 2021

Karen Sandell Sfanos, PhD, Associate Professor of Pathology, Oncology, and Urology at Johns Hopkins University, the Sidney Kimmel Comprehensive Cancer Center, and the Brady Urological Research Institute, presents and explains the results of a study conducted in her lab on the ability of bacterial infections to cause oncogenic TMPRSS2:ERG gene fusions. She begins by looking at proliferative inflammatory atrophy (PIA), which has been proposed as a risk factor that may play a key role in the development of prostate cancer (PCa). Dr. Sfanos then discusses two Science articles on the recurrent fusion of TMPRSS2 and ETS transcription factor genes in PCa and how Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Both of these articles discuss colibactin, which comes from E. coli and breaks DNA strands through DNA alkylation. Dr. Sfanos continues by analyzing a study on acute Escherichia coli prostatitis in previously healthy young men which found that over 70% of the E. coli isolate strains in patients with prostatitis contained the colibactin gene, leading directly to the hypothesis of her own study. She studied a series of cases that had active bacterial infections in the prostate at the time of prostatectomy, finding a high frequency of ERG expression in PIA lesions undescribed in scientific literature, that ERG positive PIA lesions are often found with early invasive micro adenocarcinoma, that colibactin producing bacteria were in the infected prostates, and that colibactin induces DSB at TMPRSS2 and ERG loci. Dr. Sfanos concludes that bacterial prostatitis should be considered as a risk factor for prostate carcinogenesis and that prostate infections may contribute to other oncogenic events. Dr. Sfanos then participates in a Q&A session featuring such topics as the protective potential of some of the isolates that may not be producing colibactin, research on inhibitors, and how urologists may use this information.

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