2022 Archives

Combining Therapy with SBRT and Brachytherapy

Posted by Richard G. Stock, MD | Apr 2022

Richard G. Stock, MD, Professor of Radiation Oncology and Director of Genitourinary Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, discusses the efficacy of SBRT and brachytherapy for treating patients with prostate cancer. He explains that combined SBRT and brachytherapy seems to be particularly helpful for intermediate-risk cancer, with studies showing about a 90% biochemical control rate. Dr. Stock then goes over the rationale for combined SBRT and brachytherapy, noting that brachytherapy combined with external beam radiation therapy (EBRT) at standard fractionation demonstrates excellent and safe outcomes for both intermediate- and high-risk prostate cancer, and SBRT appears to be comparable or better than standard fractionation without increased toxicity. He summarizes the findings of several different studies, explaining that with low-dose-rate brachytherapy and SBRT, researchers are seeing very similar results to using standard fractionation with brachytherapy. Dr. Stock also looks at a recent trial with high-dose-rate brachytherapy with SBRT which found a favorable early toxicity profile and encouraging cancer control outcomes. He concludes that the combination of SBRT and brachytherapy is promising, and the initial clinical impression is that patients tolerate the treatment well.

ExactVu™ Micro-Ultrasound for Diagnosis of Prostate Cancer

Posted by Priya N. Werahera, PhD | Apr 2022

Priya N. Werahera, PhD, Research Associate Professor in the Departments of Pathology and Bioengineering at the University of Colorado Anschutz Medical Campus, discusses the advantages of using the ExactVu micro-ultrasound platform to diagnose prostate cancer. First, he considers whether MRI imaging can be considered standard of care, arguing that it cannot be seen as such since many cancers are MRI-invisible, it is not cost effective, the technology remains in evolution, and there is high interobserver variability among radiologists. Dr. Werahera then turns to micro-ultrasound, explaining that the new ExactVu system is a 29 MHz machine which provides real-time imaging of prostate cancer lesions, has a high resolution of 70 microns, and can provide both lateral and axial resolution. He cites a meta-analysis which shows that micro-ultrasound is a relatively convenient and cost-effective method of real-time imaging which is highly sensitive in detecting clinically significant prostate cancer. Dr. Werahera then discusses a study at the University of Colorado comparing micro-ultrasound lesions vs. histopathology data of mapping biopsy which found that PRIMUS scores 4-5 have 100% sensitivity at the patient-level and 80% sensitivity at lesion-level for diagnosis of ≥ Gleason Grade 2 prostate cancer lesions. There were 2 undiagnosed Gleason Grade 2 lesions, both of which were small and located anteriorly. Dr. Werahera concludes that ExactVu micro-ultrasound has the potential to improve current imaging standards since it has comparable screening performance to MRI and comparable biopsy performance to MRI fusion, while also allowing for easier, more effective micro-ultrasound/MRI fusion. He also notes that ExactVu micro-ultrasound may enable widespread focal therapy due to its high accuracy in finding satellite lesions and lesion boundaries.

Impact of Rising Costs on Healthcare

Posted by Gregory F. Murphy, MD | Apr 2022

Congressman Gregory F. Murphy, MD, a practicing urologist and the Representative from North Carolina’s 3rd District, discusses rising costs and their impact on healthcare in the United States with E. David Crawford, MD, Editor-in-Chief of Grand Rounds in Urology and Professor of Urology at the University of California, San Diego. Rep. Murphy notes that the United States as a whole is currently experiencing far higher rates of inflation than it has seen in several decades, but he also highlights how healthcare in particular has seen rising costs for the past 30 years. He explains that physician debt coming out of medical school in the early 1990s was around $50,000, and is now closer to $225,000, but physician pay has increased very slowly. Rep. Murphy observes that consumer prices and hospital costs have also increased massively since the early 1990s. He blames this in part on overregulation from the government. Dr. Crawford mentions the hardships faced by small practices, many of whom have shrinking bottom lines and are being bought by venture capital firms. Rep. Murphy and Dr. Crawford opine about the difficulties new doctors and incoming medical students face in a system that seems to value them less and less, and they emphasize the need to protect medical doctors’ interests through legislation.

Pathologist’s Perspective on Biopsy Results: Transperineal Mapping vs. Fusion Biopsy

Posted by M. Scott Lucia, MD | Apr 2022

M. Scott Lucia, MD, Professor and Vice-Chair of the Department of Pathology and Director of Anatomic Pathology of the Prostate Diagnostic Laboratory at the University of Colorado Anschutz Medical Campus (CAMC) School of Medicine, compares transperineal mapping and MRI-targeted fusion biopsy to systematic biopsy for identifying prostate cancer. He explains that there is overwhelming data indicating that 12-core systematic biopsy is only about 50-65% accurate. Dr. Lucia also notes that TRUS-guided transrectal biopsy is inaccurate, often missing and under-grading significant tumors. He then introduces transperineal template-guided mapping biopsies (TTMB) as a potentially superior alternative, explaining that the PROMIS Trial demonstrated that template biopsy consistently outperforms systematic biopsy and also highlighting that template biopsy has greater concordance with results from prostatectomy. Dr. Lucia says that another option is MRI-targeted fusion biopsy, which the PRECISION trial found to have more accurate detection than systematic biopsy. He also notes that the combination of fusion biopsy and systematic biopsy performs better than either one alone. Dr. Lucia then poses the question of whether MRI-targeted fusion biopsy or TTMB is superior, and he considers data on this from several studies. He concludes: that traditional transrectal biopsy schemes are inaccurate for identifying significant cancer; that TTMB and MRI-guided targeted biopsy offer improved pathological accuracy over TRUS-guided biopsy; that TTMB offer improved pathological accuracy over MRI-fusion biopsies; and that combined systematic biopsy and MRI-guided biopsy is useful for determining eligibility for focal therapy.

Updating the Definitions, Endpoints, and Clinical Trial Designs for Bladder Cancer

Posted by Amirali Salmasi, MD | Apr 2022

Amirali Salmasi, MD, Assistant Professor of Urology at the University of California, San Diego, reviews risk stratification guidelines for non-muscle invasive bladder cancer (NMIBC) from the American Urological Association (AUA) and European Association of Urology (EAU); pointing out that the AUA classifies solitary high-grade (HG) Ta lesions ≤3cm classified as intermediate risk (IR-Ta) while the EAU recommends all HG tumors be classified as high-risk. Dr. Salmasi then presents data suggesting that, indeed, all HG Ta lesions should be considered high risk, supporting the EAU risk stratification model. He then reviews recommendations from the International Bladder Cancer Group, including definitions, end points, and clinical trial designs for NMIBC for both BCG-naive and BCG-unresponsive patients. For BCG-naive patients, Dr. Salmasi defines the clinically significant outcome of an absolute difference of 10 percent in the percentage of patients with recurrence at two years. For BCG-unresponsive patients with carcinoma in situ (CIS), a clinically meaningful magnitude of effect is an initial complete response rate of 50 percent at six months and a durable response rate of 30 percent at 12 months and 25 percent at 18 months; for those with papillary disease, it is a recurrence-free rate of 30 percent at 12 months and 25 percent at 18 months. Dr. Salmasi then shares information refining neoadjuvant therapy clinical trial design for muscle-invasive bladder cancer (MIBC) before cystectomy, citing level-one evidence that says neoadjuvant chemotherapy (NAC) should be offered to any “fit” patient before radical cystectomy (RC). He discusses eligibility and staging before discussing treatment options, posing questions about appropriate control arms for neoadjuvant trials as well as what number of neoadjuvant therapy cycles might be ideal, acknowledging that the best combination of treatment options remains uncertain. Dr. Salmasi discusses primary endpoints for neoadjuvant trials before shifting to a discussion on the future of trial design. He outlines some potential improvements to trial design, including sample size re-estimation; adaptive enrichment; seamless design; multi-arm, multistage (MAMS) trials; and biomarker-based adaptive study. Dr. Salmasi then outlines the benefits and limitations of MAMS trials and describes the characteristics of umbrella trials and basket trials. He discusses the BISCAY flowchart and the trial’s limitations and discusses the future of biomarker-based trial design in bladder cancer, citing two successful, meaningful biomarker-adaptive trials (PROOF 302 and IMvigor 011). Dr. Salmasi concludes by outlining future directions in the field, including ongoing trials for treatments for BCG-unresponsive NMIBC as well as neoadjuvant therapy for MIBC, where he asserts that work must be done to find the biomarkers of response, the need for improvements in molecular subtyping and treatment selection, and the need to identify optimal treatment. Finally, he asserts that improved patient outcomes would stem from an improved patient selection for radical cystectomy versus chemoradiation; there is also a need to continue to design adaptive trials to personalize treatment for those with metastatic urothelial cancer.