Laurence Klotz, MD, FRCSC

Laurence Klotz, MD, FRCSC

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Laurence Klotz, MD, is the former Chief of Urology at Sunnybrook Health Sciences Centre and former President of the Urological Research Society and the Canadian Urological Association. He currently serves as Professor of Surgery at the University of Toronto and holds the Sunnybrook Chair of Prostate Cancer Research. Dr. Klotz was the Founding Editor-in-Chief of both the Canadian Journal of Urology and the Canadian Urology Association Journal, and is now Editor Emeritus of the CUAJ. He is the Founder and Chairman of the Canadian Urology Research Consortium (CURC), and is also the Chair of the Global GU Oncology Group. Dr. Klotz obtained his medical degree from the University of Toronto and completed his residency at the University of Toronto Gallie Program in Surgery. He was a fellow at Memorial Sloan Kettering Cancer Center in New York in uro-oncology. Dr. Klotz is a widely published uro-oncologist with over 350 publications and several books. His main research interest has been prostate cancer. He has served on the boards of many medical/scientific organizations and journals, including the SUO, Prostate Cancer Canada, the journals Prostate Cancer and Prostatic Diseases, Brazilian Journal of Urology, Italian Journal of Urology, and World Journal of Urology. Dr. Klotz was awarded the Queen’s Jubilee Medal for meritorious public service in 2012, and the University of Toronto Department of Surgery Lister Prize and the Society of Urologic Oncology Medal in 2013. He received the Harold Warwick Award from the Canadian Cancer Society for ‘outstanding contributions to cancer control’ in 2014. He received the Order of Canada in 2015, and the Richard Williams Award from the AUA in 2016. He received the Dean’s Lifetime Achievement Award from the University of Toronto in 2017.

Disclosures:

Chief Medical Officer - miR Scientific

Articles by Laurence Klotz, MD, FRCSC

Treatment for Prostate Cancer with MRI-Guided Transurethral Ultrasound

Laurence Klotz, MD, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research, discusses MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. He characterizes this energy-based therapy as one that meets a need for patients with intermediate-risk prostate cancer, offering a less-invasive therapy with fewer quality-of-life effects than radiation and radical prostatectomy. Dr. Klotz explains the closed-loop controlled system and lays out the TULSA-PRO system components, emphasizing the power of the real-time thermal map when using thermal energy to heat tissue to destroy it. He then outlines the MRI-guided treatment workflow before listing the key features of TULSA: since it is a transurethral directional ultrasound ablation, it is incision- and radiation-free, with no energy being delivered through the rectum (thus avoiding rectal injury) and no volume limitation; the automated, closed-loop system eliminates guesswork and allows for precision, measuring temperature in real time, adjusting the amount of energy delivered to the tissue, and actively compensating for tissue and blood flow changes during the treatment; the therapy also offers thermal protection of important anatomy, including the urethra and rectum. Dr. Klotz then reviews previous TULSA technical and canine studies and the first-in-man treat and resect study for feasibility. This research led to a phase one safety and precision study that showed a 90 percent prostate-specific antigen (PSA) reduction. Dr. Klotz then reviews the TULSA-PRO Ablation Clinical Trial (TACT), which demonstrated a median PSA reduction of 95 percent, with consistent rates of biopsy-based improvement in 75-80% of men one year after TULSA therapy; data also show that TULSA therapy is easily tolerated and that most patients recover continence and erectile function within the year after therapy. Indeed, three-year follow-up data for TACT demonstrate that PSA response has been durable over time. Dr. Klotz concludes with a summary of TULSA, emphasizing the newness of this complex technology that is safe, precise, and has low toxicity. He highlights that it has been approved by the FDA and Health Canada and is emerging as a novel alternative to conventional therapy.

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Updates in ADT: Managing Adverse Effects

Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research at Sunnybrook Health Sciences Centre, reviews simple interventions physicians can use to improve quality of life and survival as well as to ameliorate unwanted side effects in prostate cancer patients undergoing androgen deprivation therapy (ADT). He explains that there are many commonly known and relatively manageable adverse effects to ADT, but that many family practitioners may not be aware of or interested in dealing with them. The responsibility therefore falls to urologists. Dr. Klotz then discusses the available and developing interventions, as well as the mechanisms of action that underlie them. First, he looks at how statins reduce the adverse effects of metabolic syndrome related to ADT by inhibiting cellular uptake of androstenediol and therefore reducing the substrate available for testosterone synthesis in the castrate environment. Dr. Klotz then considers the benefits of bisphosphonates and monoclonal antibodies like denosumab in helping with osteoporosis, another common side effect of ADT. He also looks at metformin, an inexpensive drug that appears to reduce weight gain in men on ADT, and notes that exercise is an effective way to delay progression of prostate cancer. Dr. Klotz then presents evidence supporting the use of GnRH antagonists to reduce cardiovascular events in men on ADT and discusses new research regarding the role of FSH in obesity.

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Review of Sentinel Assay for Prostate Cancer Diagnosis

Laurence Klotz, MD, FRCSC, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research, reviews the Sentinel Assay, a urine-based assay for detecting prostate cancer currently awaiting FDA approval. He notes that there are several significant needs in the pre-biopsy setting, including the need to increase the probability of a positive biopsy, and the need to reduce overdetection and the number of unnecessary biopsies. Dr. Klotz observes that there are several commercially-available biomarker assays that seek to help with this, all of which appear to work fairly well, although perhaps not quite as well as miR Scientific’s Sentinel Assay appears to. He explains that the Sentinel Assay is based on analysis of 442 urinary exosome microRNA sequences, and that it can identify small high-grade tumors that may be missed by imaging or biopsy. Dr. Klotz then summarizes the results of the one paper published on the Sentinel Assay so far, observing that its findings that the Sentinel prostate cancer test demonstrates a sensitivity of 94% and specificity of 92% are almost too good to be true. He presents as-yet-unpublished data that supports these findings, showing a 93% concordance between the Sentinel Assay and pathology. Dr. Klotz concludes that while validation is still needed, the Sentinel Assay appears to be an extremely accurate urine-based assay that will be easy to ship and use.

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

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