Neil H. Baum, MD, and E. David Crawford, MD, discuss the educational mission of GRU, as well as prostate cancer screening, detection, and treatment.
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In a 15-minute presentation that is the twelfth in a series of lectures from a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Gerard Morton, MD, FRCPC, FABS, discusses the differences between HDR and LDR brachytherapy, how HDR brachytherapy is performed, and how to select patients for HDR.
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In this 12-minute presentation, Peter F. Orio III, DO, MS, Vice Chair of Network Operations for Dana-Farber/Brigham and Women’s Cancer Center Department of Radiation Oncology and Associate Professor of Radiation Oncology at Harvard Medical School in Boston, Massachusetts, explains prostate brachytherapy is effective, efficient, and convenient, and he says it is “the right thing to do for patients.” He sees a threat to patients posed by radiation oncology without brachytherapy and concludes by encouraging urologists to explore a broad range of treatments to maximize the benefit to patients.
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Matthew R. Cooperberg, MD, MPH, Professor of Urology and Epidemiology & Biostatistics and Helen Diller Family Chair in Urology at the University of California, San Francisco, explores a range of biomarkers used for diagnosis, risk stratification, and guiding treatment for prostate he cancer. He first details pre-biopsy diagnosis or prostate cancer, including PSA, 4K, phi, MyProstateScore, ExoDX, SelectMDx, and mpMRI. Dr. Cooperberg discusses how post-diagnosis biomarkers must be shown to improve on an existing, validated, multivariable model reflecting all available clinical information rather than on a single variable or nonlinear risk grouping, and reviews post-diagnosis options for risk stratification and treatment.
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Daniel G. Petereit, MD, FASTRO, reviews brachytherapy and ABS initiatives to train physicians capable in administering the treatment.
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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.
Read MoreLaurence 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.
Read MoreAs part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Peter F. Orio III, DO, MS, Vice Chair of Network Operations for Dana-Farber/Brigham and Women’s Cancer Center Department of Radiation Oncology and Associate Professor of Radiation Oncology at Harvard Medical School in Boston, Massachusetts, discusses socioeconomic influences on the use of prostate brachytherapy. He begins by listing nine factors that he believes have led to a decline in the use of prostate brachytherapy: (1) a decrease in PSA screening and prostate cancer diagnosis; (2) an increase in patients electing active surveillance; (3) Nuclear Regulatory Commission requirements; (4) an increase in the number of robotic prostatectomies; (5) a suboptimal volume of prostate brachytherapy procedures being performed; (6) negative press about brachytherapy from procedures performed at the Philadelphia VA; (7) the increased technical sophistication of external beam radiation technologies; (8) a lack of knowledge of brachytherapy’s efficacy; and, most significantly, (9) markedly decreased reimbursement rates for brachytherapy. Focusing on this last point, Dr. Orio considers a report by the Government Accountability Office which found that if there was a self-referring interest in a center that offered intensity-modulated radiation therapy (IMRT), use of IMRT would increase by about 50%, while radical prostatectomies would decrease by 27% and brachytherapy procedures would decrease by 50%. He explains that in a fee-for-service model, a treatment like brachytherapy which requires one implant is reimbursed for far less than a treatment like IMRT which requires weeks of treatment over the course of multiple sessions. This creates, Dr. Orio argues, a disincentive to perform brachytherapy even though it is less expensive and results in better quality of life than IMRT. He suggests that implementation of the radiation oncology alternative payment model (RO-APM) may solve this problem. Dr. Orio explains that the RO-APM, which is being tested in certain zip codes, represents a shift to value-based care and is intended to simplify coding and reduce Medicare costs. Under the RO-APM, he notes, regardless of the modality of treatment, the payment is the same, so brachytherapy monotherapy will likely benefit from an increase in payment. Dr. Orio concludes that the RO-APM may lead to a resurgence in prostate brachytherapy by removing financial disincentives to performing the procedure.
Read MoreAs part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society and Grand Rounds in Urology, Mira Keyes, MD, FRCPC, FABS, Clinical Professor at the University of British Columbia (UBC) and a radiation oncologist at the Vancouver Centre of the British Columbia Cancer Agency (BCCA), discusses the pros and cons of using androgen-deprivation therapy (ADT) with brachytherapy to treat prostate cancer. After briefly discussing how ADT affects the tumor microenvironment, Dr. Keyes goes over the numerous clinical trials that have investigated how to combine external beam radiation together with hormone therapy. She explains that these trials found that the combination increases overall survival ~10-13% over ADT or EBRT alone, and longer ADT has a greater impact on OS, even with high radiation therapy dose. Dr. Keyes observes that ASCO considers brachytherapy a standard of care and recommends it be combined with ADT for unfavorable intermediate-risk and high-risk disease. She then considers the findings of ASCENDE-RT, the HDR UK trial, and the TROG 0.304 RADAR trial, all of which looked at the combination of ADT and brachytherapy, and discusses several ongoing randomized controlled trials on the role of ADT with prostate brachytherapy. Dr. Keyes also discusses a systematic literature review of ADT + prostate brachytherapy which concludes that the addition of ADT to brachytherapy provides no benefit to cancer-specific survival with ADT, and no benefit to overall survival with ADT, but does provide up to a 15% benefit to biochemical progression-free survival. She also notes that some believe dose escalation (prostate brachytherapy boost) may obviate the need for ADT in some high-risk patients. Dr. Keyes looks at a different meta-analysis which found that the addition of ADT to external beam radiation therapy provided a greater oncologic benefit than a brachytherapy boost and that there was a high probability that intermediate-risk and high-risk prostate cancer treated with EBRT + ADT would have superior overall survival to high-risk patients treated with EBRT + brachytherapy boost. Dr. Keyes argues that this paper misses the fact that the benefit of brachytherapy is that if brachytherapy is used, the duration of ADT can be reduced in unfavorable intermediate-risk and high-risk patients, which has a significant positive impact on quality of life and overall survival. She notes that ADT has numerous negative effects on quality of life, including erectile dysfunction, dementia, osteoporosis, metabolic syndrome, and more. Dr. Keyes particularly focuses on the negative cardiovascular effects from ADT, noting that observational data shows excess cardiovascular morbidity and mortality in patients on ADT with pre-existing cardiovascular disease. She concludes that ADT should be avoided in low- and intermediate-risk prostate cancer patients treated with monotherapy, that ADT for only 12 months in unfavorable intermediate- and high-risk patients is supported by randomized controlled trials, that ADT can be omitted in selected unfavorable intermediate- and high-risk patients, and that shorter ADT duration will improve quality of life and may increase overall survival by decreasing cardiovascular disease morbidity.
Read MoreAs part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Peter F. Orio III, DO, MS, Vice Chair of Network Operations for Dana-Farber/Brigham and Women’s Cancer Center Department of Radiation Oncology and Associate Professor of Radiation Oncology at Harvard Medical School in Boston, Massachusetts, discusses brachytherapy’s role in treating high-risk prostate cancer (PCa). He shares the largest prostatectomy series to report cause-specific survival (CSS) by biopsy Gleason score (and the largest prostatectomy series to report CSS in the prostate-specific antigen [PSA] era), highlighting data that demonstrate that men with T3 disease have a 38 percent chance of prostate-cancer-specific mortality (PCSM) and men with a Gleason score of 8-10 have a 34 percent chance of PCSM. Further, long-term surgical biochemical progression-free survival (bPFS) among men with a Gleason score of 8-10 is on the order of 30-40 percent. Dr. Orio then displays data from a comparative analysis of PSA-free survival outcomes for patients with high-risk PCa by radical therapy. It shows that external-beam radiation therapy (EBRT) with brachytherapy (with or without androgen-deprivation therapy [ADT]) has better PSA-free progression than do other radical therapies. He cites data that show when brachytherapy is added to EBRT, patient outcomes improve. He then introduces three clinical trials examining EBRT with and without brachytherapy to examine more closely. In the first trial, at a median follow-up of 8.2 years, patients treated with EBRT with a brachytherapy component had half the biochemical failure compared with patients treated with EBRT alone. Similarly, another randomized trial of EBRT alone or combined with high-dose brachytherapy boost showed similar improved outcomes, with better biochemical relapse-free survival at five, seven, and 10 years for patients who underwent the combined therapy. Dr. Orio then turns to the ASCENDE-RT Trial, which compared a low-dose-rate prostate brachytherapy (LDR-PB) to a dose-escalated EBRT (DE-EBRT) for patients with high- and intermediate-risk PCa. Data showed a benefit to the LDR-PB, with an absolute difference in the proportion of patients free of recurrence of nearly 21 percent at nine years. Similar results occurred among intermediate-risk patients and high-risk patients. Dr. Orio goes on to compare the progression-free survival at seven years among high risk patients who received the LDR-PB (83 percent) with the surgical bPFS of 30-40 percent, concluding that brachytherapy can spare many men the need for salvage therapies. He then addresses toxicity concerns about the LDR-PB, explaining that practitioners should avoid the dragging of seeds to the membranous urethra, where they have the potential to cause a urethral stricture. Dr. Orio explains that doctors can decrease toxicity by identifying the apex of the prostate, making it easier to control placement of the seeds and avoid toxicity. He goes on to explain other solutions to reduce toxicity such as using a gel spacer between the prostate and the rectum. Dr. Orio cites one additional study confirming that EBRT with brachytherapy leads to better patient outcomes compared with radical prostatectomy or EBRT alone. Dr. Orio advises that patients with intermediate- or high-risk PCa receiving EBRT +/- ADT should be offered brachytherapy as a dose escalation strategy because it is proven with Level 1 evidence. He explains that the American Society of Clinical Oncology (ASCO) stated that eligible intermediate- and high-risk PCa patients choosing EBRT with or without ADT should be offered brachytherapy. Dr. Orio states that a rising PSA condemns many men to expensive, toxic, and quality-of-life-reducing treatments and asks if society is prepared for this cost to normalize overall survival. He asserts that we should instead consider using brachytherapy in those with higher-risk disease.
Read MoreAs part of a special course on brachytherapy for prostate cancer from the American Brachytherapy Society (ABS) and Grand Rounds in Urology, Michael J. Zelefsky, MD, Vice Chair of Clinical Research in the Department of Radiation Oncology and Chief of the Brachytherapy Service at Memorial Sloan Kettering in New York City, compares outcomes for prostate brachytherapy vs. external-beam radiation therapy (EBRT) vs. stereotactic body radiotherapy (SBRT) for patients with low- and intermediate-risk disease. Dr. Zelefsky explains that when comparing outcomes, the focus is on toxicity after therapy and the efficacy of therapy. He also notes several limitations in comparing different radiotherapeutic modalities as well as dramatic technological innovation over the last 10 years that have greatly improved radiotherapy delivery. While this has been revolutionary in the treatment of disease, it creates what he calls “a moving target” when comparing outcomes because of the difficulty in comparing studies completed at various points in this technological revolution. Dr. Zelefsky cites a comparative study of patient-reported quality-of-life (QOL) outcomes after SBRT, low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy for prostate cancer. Another study compared patient-reported QOL following SBRT and conventionally fractionated EBRT compared with active surveillance in those with localized prostate cancer. He reviews highlights from five-year outcomes of the HYPO-RT-PC randomized, non-inferiority, phase 3 trial that examined ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer, including that the estimated failure-free survival at five years was 84 percent in both treatment groups. Dr. Zelefsky notes that genitourinary and gastrointestinal toxicity were similar in both groups as well. He presents a chart illustrating urinary symptoms post-therapy which shows that while LDR has a higher rate of acute grade two urinary symptoms, late urinary toxicity and late urinary incontinence are similar across LDR, EBRT, and SBRT. Dr. Zelefsky outlines the benefits of prostate brachytherapy for favorable and intermediate-risk disease, pointing out that it has the most ablative potential, prostate-specific antigen nadirs are generally significantly lower than with EBRT, and post-treatment biopsy outcomes are positive in just seven percent of patients. He compares this with data showing that EBRT results in post-treatment positive biopsy outcomes of approximately 25-30 percent and data showing that SBRT with a dose of 40 Gy results in post-treatment positive biopsy outcomes of 11 percent. Dr. Zelefsky suggests then that SBRT has more ablative potential than EBRT but that brachytherapy has even more ablative potential than either of these. Finally, Dr. Zelefsky summarizes by explaining how these findings help inform patient decisions and treatment selection, pointing out that prostate brachytherapy may be preferable for the younger patient with few urinary symptoms, while patients with significant urinary symptoms may prefer SBRT. Patients with a larger prostate who may otherwise require downsizing with ADT may opt for SBRT over brachytherapy.
Read MoreMark Emberton, MD, FRCS, Professor of Interventional Oncology at University College London, summarizes the design and findings of a 15-year multi-institute study of high-intensity focused ultrasound (HIFU) in patients with nonmetastatic prostate cancer. After an introduction from E. David Crawford, MD, Professor of Urology at the University of California, San Diego, and Editor-in-Chief of Grand Rounds in Urology, Dr. Emberton notes that the results of this 15-year study resulted in a wave of positive press about HIFU in popular outlets, observing that this widespread enthusiasm is due not just to HIFU’s efficacy, but its safety and adverse event profile as well. He then details the design of the study, beginning with the patient profile. Noting that outcomes in prostate cancer treatment are largely dependent on the risk profile of the patient, Dr. Emberton explains that in this study the average patient age was 66, ⅕ of patients had a PSA greater than 10, the average prostate volume was relatively low, the majority of patients were Gleason 3+4, and the majority of patients were T2. He mentions that intervention varied, and that while the majority of patients had quadrant ablation, about ⅓ had hemiablation. Dr. Emberton then considers the outcomes, observing that the “headline” of the study was the 83% 5-year failure-free survival for intermediate-risk disease. He also highlights that only 0.5% of patients experienced greater than 2 adverse events. Dr. Emberton discusses some supplementary data, emphasizing that if a clinician commits to HIFU, they also commit to retreating a subset of patients. He concludes that HIFU is very safe and that the data suggests that the majority of eligible patients with intermediate-risk disease can defer or avoid radical therapy with HIFU.
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