Topic: Prostate Cancer

Current Status of PSMA Diagnostics

by Jeremie Calais, MD, MSc | Aug 2021

Jeremie Calais, MD, MSc, Assistant Professor and Director of the Clinical Research Program in the Ahmanson Translational Theranostics Division of the Department of Molecular and Medical Pharmacology at UCLA, discusses PSMA diagnostics and compares imaging modalities to establish which modality is ideal for prostate cancer staging. He shares the FDA guidelines, stating that Ga 68 PSMA-11 is to be used for patients with prostate cancer (PCa) with suspected metastasis who are candidates for definitive therapy, and with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. Dr. Calais summarizes two trials used to support FDA approval of the diagnostic agent, including one on biochemical recurrence localization showing an overall detection rate of 75%, and another on primary nodal N1 staging that shows a sensitivity of 40% and a specificity of 95% for Ga 68 PSMA-11. Dr. Calais also notes the weaknesses of PSMA-11, including PET/CT’s inability to detect microscopic cancer cells, the way bone trauma in the ribs can lead to false positives, the challenge of accurately reading faint uptake lymph nodes, and how urine can disrupt analysis of the prostate fossa. Dr. Calais then compares PSMA against fluciclovine, finding that PSMA has a 30% higher detection rate; and against conventional imaging, finding that PSMA has a 27% higher rate of accuracy, as well as higher sensitivity and specificity. He also compares PSMA and local staging with MRI, highlighting a study on intra-prostatic tumor detection that shows a negligible difference in detection rates, as well as two studies on PSMA PET for biopsy guidance that show PSMA PET’s effectiveness in detecting especially challenging cancer. Dr. Calais concludes that PSMA PET/CT should replace other imaging modalities for prostate cancer staging and should be used as a complement to MRI for intra-prostatic tumor detection and staging.

Genetic Testing and Prostate Cancer

by Raoul S. Concepcion, MD, FACS | Aug 2021

Raoul S. Concepcion, MD, FACS, Chief Science Officer of U.S. Urology Partners in Nolensville, Tennessee, discusses genomics and DNA repair within the context of prostate cancer treatment to demonstrate the ability of next generation sequencing (NGS) to improve patient outcomes. He begins by giving basic definitions of genetics, genomics, and the genome before sharing data that supports an argument for performing genetic testing. Dr. Concepcion reviews studies on several related topics that all show higher rates of germline mutations in patients with metastatic and/or high-grade cancer. Dr. Concepcion explains that the link between germline mutations and higher rates of metastatic and higher-grade cancer shows that understanding DNA mutations and genomics can improve treatment. He then gives an overview of genomics, explaining how genetic code is formed and behaves and the different types of DNA mutations. He also gives an example of a pathogenic report expressing a nonsense mutation. Dr. Concepcion reviews the American College of Medical Genetics and Genomics (ACMG) classification system and how including testing as a part of treatment plans will improve that system. He then discusses the Knudson “two-hit” model hypothesis, presents data demonstrating that 60% of metastatic cancer patients do not undergo molecular testing, and explains that patients treated with targeted therapies based on genetic testing have 63% longer overall survival than other metastatic patients. Dr. Concepcion concludes by observing that an understanding of modern-day genomics and DNA repair is crucial to improving treatment.

What’s New in Active Surveillance for Prostate Cancer in 2021

by Laurence Klotz, MD, FRCSC | Aug 2021

Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto and the Chair of Prostate Cancer Research at Sunnybrook Health Sciences Centre, discusses what is new with active surveillance (AS) for prostate cancer, presenting various recent studies. He begins by considering the role of molecular genetics and observes that patients with certain kinds of disease are very safe candidates for AS noting, for instance, that only 2% of patients with Gleason grade 1 cancer are in the highest average genetic risk quartile, and that long-term outcomes for patients with Gleason grade 1 disease on AS are excellent. Dr. Klotz then looks at the safety of AS for younger patients, a group that has often been encouraged to get radical treatment, and highlights studies showing that younger men have a lower risk of upgrading while on AS and that AS is as safe for men over 60 as it is for men under 60. He comments on some other commonly-cited risk factors, noting that, with the exception of patients with BRCA mutations, a family history of prostate cancer does not increase a patient’s risk of having more aggressive prostate cancer, and also that while Black men experience higher rates of progression and treatment on AS, there is no difference in metastasis or mortality compared to White men on AS. Dr. Klotz acknowledges that radical treatment is likely necessary for patients with the BRCA2 mutation, but mentions that there is some controversy in this area. He then touches on the limitations of MRI, emphasizing that MRI progression does not correlate with upgrading and that MRI does not contribute significantly to the identification of higher-grade cancer, and that biopsy compliance is important for identifying progression. Dr. Klotz also briefly notes that active surveillance is a safe option for well-selected patients with intermediate-risk disease. He then looks at some recent research indicating a relationship between obesity and prostate cancer progression. Dr. Klotz concludes with the observation that while there is still a lot of variation in the use of active surveillance, as well as room for growth, there has been increased uptake overall in the US.

Next Generation Imaging for Prostate Cancer

by Phillip J. Koo, MD | Aug 2021

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.

Update on New Approaches Combining Brachytherapy with Immunotherapy

by Steven E. Finkelstein, MD, FACRO | 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.

Diet Only and Prostate Cancer

by Mark A. Moyad, MD, MPH and A. Karim Kader, MD, PhD | 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.

Surveillance After Image-Targeted Focal Therapy

by Thomas J. Polascik, MD, FACS | 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.

PCa Commentary | Volume 155 – July 2021

by Edward Weber, MD | Jul 2021

This Commentary looks at causes and management options for hot flashes, a common side effect of ADT treatment for prostate cancer.

Evaluation and Management of Localized and Recurrent Prostate Cancer: Genetic Cancer Profiling

by Alan Pollack, MD, PhD | Jul 2021

Alan Pollack, MD, PhD, Professor and Chair in the Department of Radiation Oncology at University of Miami Health, looks at genetic cancer profiling for prostate cancer risk assessment and its implications for treatment. He begins with a discussion of the development of a habitat risk scoring system for prostate cancer which, via quantitative pixel by pixel assessment, can generate high-risk volumes for targeting. Dr. Pollack then moves on to transcriptome analysis using genomic classifiers like Decipher, noting that these classifiers have a relationship with Gleason score, though it is not absolute, and can predict 10-year distant metastasis. He also considers how to understand genomic risk of habitats from quantitative MRI, observing the significant connections between radiogenomic features and transcriptomic features. Dr. Pollack concludes with a discussion of how genomic signatures might influence critical management, going through how Decipher scores could change risk stratification and highlighting several trials looking at habitat targeted radiotherapy.

MRI-US Fusion Target Management of Prostate Cancer in the Office Setting

by Fernando J. Bianco, MD | Jul 2021

Fernando J. Bianco, MD, Investigator-in-Chief for the Urological Research Network in Miami, Florida, discusses treatment of prostate cancer using MRI-ultrasound fusion biopsy in an office setting. Dr. Bianco remarks how the results of the PIVOT and ProtecT trials have shifted the emphasis away from radical prostatectomy to focal therapy. The next consideration has been whether the procedure could be done in an office setting if sedation or anesthesia were not needed. The development of a transperineal block allowed physicians to perform biopsy and treatment in-office under local anesthesia. Dr. Bianco then describes his technology, Focalyx® Fusion, which uses MRI-ultrasound fusion to diagnose, biopsy, and then treat using cryoablation. The combination of MRI and ultrasound fusion during treatment provide the physician with a clearer picture of the treatment in real-time. The technology utilizes programmed workflows to prioritize patients and also shares procedure results back to the patients via an app. He notes that patients show a drop in PSA, improved urinary function, and no major deterioration in rectal performance following the procedure. Dr. Bianco also discusses current research to determine whether prophylactic antibiotics before a transperineal prostate biopsy are necessary.

Current and Emerging Role of Radiogenomics in Risk Assessment

by John Feller, MD | Jul 2021

John Feller, MD, Founding Partner and Medical Director of Desert Medical Imaging, Assistant Clinical Professor in the Departments of Radiology at Loma Linda University and at Riverside School of Medicine, Chief of Radiology and Partner of the American Medical Center in China reviews data for evaluating radiogenomics in terms of risk stratification for focal therapy and for developing novel combination therapies. Dr. Feller introduces a phase II study on laser focal therapy of prostate cancer that shows the ability of responders to focal therapy to be distinguished from non-responders with support from findings showing lower PSA values and lower PSA density in responders as opposed to nonresponders, and another study on the Decipher Genomics Resource Information Database (GRID), revealing that genes can be used to differentiate responders from non-responders. He then discusses a phase II clinical trial on outpatient trans-rectal MR-guided Laser Focal Therapy that found that short-term and intermediate-term oncologic control achievable in 79% of patients with initial treatment. He concludes that MpMRI followed by genomics shows promise for risk stratification for focal therapy and that multiple complex data sources present an opportunity for artificial intelligence.

Pay for Performance Model to Improve Quality of Active Surveillance in Low-Risk Prostate Cancer

by Franklin Gaylis, MD, FACS | Jun 2021

In the final installment of a 3-part series, Franklin Gaylis, MD, FACS, Chief Scientific Officer of Genesis Healthcare Partners and Voluntary Professor of Urology at the University of California, San Diego, reviews measures derived from a project looking at the value of a pay for performance model in improving the quality of active surveillance in low-risk prostate cancer. He also considers the utility, simplicity, and economy of using an electronic medical record-embedded template. Dr. Gaylis concludes by suggesting that government entities and physicians should collaborate to create the best medical standards and practices possible as the US healthcare system makes the transition from volume to value.

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PDF Embedder Test Jan 2022
Genetic Testing and Prostate Cancer – Welcome Jan 2022
Current Status of PSMA Diagnostics Aug 2021
Genetic Testing and Prostate Cancer Aug 2021
What’s New in Active Surveillance for Prostate Cancer in 2021 Aug 2021