Laurence Klotz, MD, FRCSC

Laurence Klotz, MD, FRCSC

University of Toronto

Toronto, Ontario, Canada

Laurence Klotz, MD, FRCSC, is a professor of surgery at the University of Toronto and 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 (CUAJ), and he is now editor emeritus of the CUAJ. Dr. Klotz obtained his medical degree and completed his residency at the University of Toronto. He was also a uro-oncology fellow at Memorial Sloan Kettering Cancer Center in New York.

Dr. Klotz has 550 peer review publications and eight books. He coined the phrase “active surveillance” and successfully championed this approach for men with favorable-risk prostate cancer against substantial resistance. He was the associate editor of the Journal of Urology, responsible for prostate cancer, for eight years. Dr. Klotz received the Queen’s Jubilee Medal for outstanding public service, the University of Toronto's Lister Prize, the Society of Urologic Oncology’s SUO Medal, the American Urological Association’s Richard Williams Award, the University of Toronto's Lifetime Achievement Award, the Canadian Urological Association Lifetime Achievement Award, and the Harold Warwick Award from the Canadian Cancer Society for “outstanding contributions to cancer control.” In 2015 he was inducted as a Member of the Order of Canada, Canada’s highest civilian award.

Disclosures:

Research Support: Sanofi-Aventis, AbbVie, Exact Imaging
Honorarium Recipient: AstraZeneca, TerSera, Sanofi-Aventis
Consultant: miR Scientific

Talks by Laurence Klotz, MD, FRCSC

Alan W. Partin Distinguished Lecture: The Genomics and Natural History of Visible vs. Invisible Cancers

Laurence Klotz, MD, FRCSC, presents the newly-emerging and provocative concept of MRI visibility as a predictor of prostate cancer tumor aggressivity in the Alan W. Partin Distinguished Lecture at IPCU 34. Given that more definitive data on the subject develops, and the urological community accepts it, this could imply significant changes to practice.

Currently, the concern over invisible cancers drives a lot of interventions, such as systemic biopsies in patients who have already undergone targeted biopsies and/or received negative imaging results.Patients on active surveillance derive anxiety from the possibility of having untreated occult cancer.

The clinical implication of imaging-based monitoring has many advantages, such as psychological benefit to the patient, and reduced cost and burden of care from avoiding systematic biopsies. Recent genomic and clinical studies support the idea that tumors invisible on MRI imaging have much more favorable genetics and natural history than those visible on MRI. This implies that in imaging-based management, the occasional missed cancers are not meaningful.

Many exciting genetic studies over the past six years have demonstrated merit to this theory, including a study identifying four genes predicting progression-free survival, metastases-free survival, and MRI visibility; a study correlating cancer aggressiveness and quantitative imaging features; and a correlation analysis of hypoxia-related genes and biparametric MRI visibility. A study from University of California, Los Angeles defined the term Nimbosus—a word derived from nimbus storm clouds—to describe an aggressive pathological, molecular, and microenvironmental phenomenon. This data suggested a confluence of the adverse features that make up nimbosus and MRI visibility.

However, there are still many unmet needs in this area, including an interrogation of uncommon invisible aggressive cancers, existing databases for robust data on invisible versus invisible cancers, and alternative imaging modalities like micro-ultrasound and PSMA-PET. As radiogenomics are still in their infancy, further, more definitive research must occur before adopting this into practice.

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Management of Disease Recurrence in Localized Prostate Cancer

Laurence Klotz, MD, FRCSC, discusses the complexities surrounding salvage therapy and focal therapy. Dr. Klotz explores the challenges that arise when managing local failure after radiation, providing insights into the polarized perspectives on the significance of focal therapy. He highlights the striking similarities in disease control achieved through various modalities of salvage therapy, shedding light on the potential benefits of radiation in mitigating genitourinary (GU) and gastrointestinal (GI) toxicity.

Dr. Klotz emphasizes the need to redefine treatment goals in focal therapy, urging a shift towards preventing metastasis and mortality as primary objectives, rather than seeking complete cancer eradication. Furthermore, the presentation discusses the captivating concept of “invisible tumors” and their favorable genetic features, aligning with the emerging principles of image-based management and its integration with focal therapy, allowing for personalized, targeted treatments that hold promise for improved patient outcomes.

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Active Surveillance 2022: Who Qualifies, Who Does Not and How Should it be Monitored

In this 12-minute presentation, Laurence Klotz, MD, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research, outlines recent progress in active surveillance (AS), highlighting molecular genetics of GG1 vs. higher grade cancers, patient selection, germline testing, imaging, biomarkers, predictive nomograms, modeling, long-term outcomes, follow-up strategies, the tumor microenvironment, and dietary modifications. Dr. Klotz summarizes current AS follow-up strategy and explains that an emerging strategy is dynamic risk profiling with accurate biomarkers that will replace most serial biopsies.

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MRI-guided Transurethral Ultrasound Ablation (TULSA) for Prostate Cancer

Laurence Klotz, MD, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research, discusses the technology, procedure, outcomes, and regulatory environment surrounding MRI-guided transurethral ultrasound ablation (TULSA) treatment for patients with prostate cancer. He begins by displaying a chart of multiple minimally invasive treatment options for prostate cancer. Dr. Klotz lists prospective studies of focal therapy that found relatively few adverse quality-of-life (QOL) effects. He goes on to compare five ultrasound-based technologies in terms of biopsy and prostate-specific antigen (PSA) outcome, concluding that data demonstrates these therapies work. Dr. Klotz emphasizes that there is not currently a way to differentiate the oncological efficacy of these treatments, citing the number of variables and reiterating that they all are reasonably effective. Dr. Klotz then turns the discussion to MRI-guided transurethral ultrasound ablation (TULSA), explaining the function of the technology and the system components involved, explaining that the energy delivered is controlled by a closed-loop control system. He outlines the key features of the TULSA system, explaining that it delivers transurethral directional ultrasound ablation which is incision and radiation free, and there is no energy coming through the rectum and there is no volume limitation. Further, real-time MRI thermal dosimetry and ablation control means temperature is measured in real time and the system adjusts the amount of energy delivered to the tissue, providing precision, actively compensating for tissue and blood flow changes during the treatment. Finally, the system offers thermal protection of important anatomy (i.e., urethra and rectum cooling). Dr. Klotz then outlines the evolution of the TULSA technology, including technical studies, canine studies, first-in-man treatment, and feasibility studies. He describes the TULSA-PRO Ablation Clinical Trial (TACT), which involved 115 patients across 13 institutions in five countries, with safety (frequency/severity of adverse events) and efficacy (PSA reduction ≥75 percent in >50 percent of patients) being the primary endpoints at 12 months. Ninety-six percent of patients had a PSA reduction ≥75 percent at 12 months and at the 12-month MRI the median prostate volume had decreased from 41 to 4 cc (a decrease of 90 percent). Further, the treatment preserved continence and erectile function. In a three-year follow-up among men who underwent the treatment, just 11 percent needed salvage treatment. Dr. Klotz explains the challenges involved in demonstrating level-one evidence for the benefit of new technologies since benefits tend to be incremental and gradual. He cites the da Vinci robot as an important example and explains that the U.S. Food and Drug Administration (FDA) has acknowledged this in its approval of high intensity focused ultrasound (HIFU) and TULSA (for tissue ablation). Dr. Klotz concludes with a summary of the TULSA technology, procedure, outcomes, and regulatory considerations, explaining that this new technology is being offered in the US and Europe and is pending in Canada.

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Active Surveillance or Focal Therapy as Primary Management

Laurence Klotz, MD, Professor of Surgery at the University of Toronto and the Sunnybrook Chair of Prostate Cancer Research, addresses when it is appropriate to use focal therapy versus active surveillance (AS) for prostate cancer. He observes that focal therapy for prostate cancer is controversial, with some doubting its efficacy entirely, and gives the disclaimer that he approaches the subject as an advocate for focal therapy in certain cases. Dr. Klotz then discusses the goals of AS, explaining that for de novo Gleason grade 1 patients, the purpose is to identify higher grade cancer, and for Gleason grade 2-3, the goal is identification of clinical progression while the disease is still curable. He notes that with AS, historically the risk of ‘progression’ to higher grade cancer has been 40%, while with focal therapy, the risk of failure is 35-40%, meaning that the risk of unrecognized/persistent GG ≥ 2 is similar for both. Dr. Klotz then considers the uses and appeal of focal therapy, emphasizing the benefits of a treatment that preserves the prostate and also allows time to intervene if the cancer returns. He also mentions some of the misuses and risks of focal therapy, arguing that it can be difficult to use in cases of tumor multifocality and heterogeneity and that the significant limitations of imaging and targeting, especially for Gleason grade 2 disease, can be challenging. Additionally, Dr. Klotz highlights the lack of level 1 evidence supporting focal therapy. He goes on to discuss what makes good candidates for partial gland ablation, describing patients with a Gleason grade 2 solitary unilateral lesion as being in the ‘sweet spot’ for focal therapy, while patients with more widespread or slightly higher grade disease may be candidates, but not necessarily. Dr. Klotz would not advise partial gland ablation to young patients with high-volume Gleason grade 1 unilateral disease who have a clear target on MRI, or to patients with Gleason grade 4 disease who have a small solitary lesion on biopsy and MRI. He then discusses the current management protocols for both AS and focal therapy in detail before concluding with a look at the future of focal therapy. Dr. Klotz argues that, despite the controversies, patients will increasingly demand focal therapy and therefore the urology field has a mandate to confirm its oncologic effectiveness and safety, and to determine which of the many methods of focal therapy is best.

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