Alan H. Bryce, MD, presents results from the TRITON3 study comparing the efficacy of a PARP inhibitor (rucaparib) against docetaxel in mCRPC treatment. Dr. Bryce reviews the study design, emphasizing the options presented to the study participants in both treatment arms. The study yielded evidence that rucaparib might be superior to docetaxel-containing treatments.
Read MoreAlan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, discusses genetic testing, next generation DNA sequencing, and the genetic diversity of prostate cancer (PCa) in regard to treatment. He begins by reviewing the germline BRCA mutations, stating that BRCA1 and BRCA2 mutations individually make up fewer than 1.3% of all cases of localized PCa. Dr. Bryce then discusses BRCA2 in detail, focusing on how BRCA2 carriers are considered high risk by the NCCN guidelines, which recommend PSA screening discussions to start at age 45. He evaluates traditional guidelines in the context of germline mutations, finding that genetic testing and Gleason score guidelines do not reliably identify PCa patients for the presence/absence of high-risk germline mutations. Dr. Bryce then discusses the mutational landscape by disease state, displaying how PCa evolves as it advances to become metastatic and castration resistant and supporting the idea that a genomic understanding of an individual’s disease is key to treatment. He reviews the approval of olaparib, a PARP inhibitor, and the PROfound trial. Dr. Bryce concludes that inherited prostate cancer risk syndromes are under-recognized, both in practice and in research, that PCa is genetically diverse, that the impact of treatments on tumor evolution should be evaluated, and that multiple new pathways for therapeutic targeting have been identified.
Read MoreTaking the con side in a point-counterpoint debate, Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, argues that offering neoadjuvant chemotherapy (NAC) to patients with invasive bladder cancer prior to radical cystectomy (RC) may not always be the appropriate decision. He begins by considering what the debate even is, explaining that the NCCN considers NAC followed by radical cystectomy a category 1 recommendation based on high level data. Meanwhile, Dr. Bryce notes, adjuvant chemotherapy is only considered a category 2A recommendation. However, he continues, the NCCN guidelines also mention that patients with “hearing loss or neuropathy, poor performance status, or renal insufficiency may not be eligible for cisplatin based therapy,” and if “cisplatin based therapy cannot be given, neoadjuvant therapy is not recommended.” Dr. Bryce also argues that while clinical trial data strongly favors NAC, real-world patient populations are different from trial populations. He cites a study based on real-world data which found that the patients in the SWOG trial of NAC were younger and fitter compared with national numbers, and which found the survival benefit with NAC to be slight in retrospective data. Additionally, Dr. Bryce observes that about 33 to 41% of patients are ineligible for cisplatin due to their baseline renal function status. He notes that those patients might benefit from adjuvant chemotherapy, but acknowledges there have been few randomized controlled trials in this setting. Dr. Bryce then highlights toxicity issues related to NAC, including increased creatinine, decreased neutrophil, peripheral sensory neuropathy, and tinnitus. He concludes that because real-world patients are older and have more comorbidities than trial populations, NAC perhaps should not be used as widely as guidelines indicate.
Read MoreRana R. McKay, MD, Associate Professor of Medicine at the University of California, San Diego, and Co-Leader of the Genitourinary Oncology Disease Team at the Moores Cancer Center, and Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, debate whether to treat metastatic castration-resistant prostate cancer (mCRPC).
Taking the pro position, Dr. McKay presents on why physicians need to treat mCRPC, as well as come up with additional treatment options to help improve survival for mCRPC patients. She discusses the goals of mCRPC treatment, improved quality of life and overall survival, and displays a chart that summarizes the current landscape of treatment for advanced prostate cancer as she details how androgen receptor (AR) targeting agents are enhancing treatment. Dr. McKay reviews FDA-approved agents in mCRPC, stating that the vast majority both improve overall survival and quality of life. She specifically states that the agents, outside of pembrolizumab, rucaparib, and sipuleucel-T, can potentially increase overall survival by 53.6 months and improve cancer-associated pain, disease-related urinary symptoms, and symptomatic skeletal events. Dr. McKay then shows a graph displaying mCRPC treatment in a clinical practice, suggesting that mCRPC is grossly undertreated based on the vast majority of patients not going beyond first-line treatment. She states that there is little reliable data on the cost effectiveness of treatment and concludes that mCRPC should be treated based on data showing that treatments improve overall survival and quality of life.
Taking the con position, Dr. Bryce makes an argument against treating mCRPC based on the differences between trial and real-world populations, and the challenges of extreme treatments. Dr. Bryce cites quality of life post-treatment, financial toxicity, and patient-centric treatment as cons of mCRPC treatment. He shows a graph of mCRPC treatment management in clinical practice and states that the rapid drop off after first-line therapy could be caused by patient drop outs instead of undertreatment. Dr. Bryce discusses the mCRPC treatment process in detail, focusing on how after the first line of therapy, treatment options become much more extreme and mostly consist of chemo, and most patients only have about a year left to live if they are beyond second-line treatment. He uses a case study of a 73-year-old patient to show how real-world patients can differ from selected trial patients due to how patient selection leads to optimized outcomes. Dr. Bryce reviews data showing that 20% of patients report financial toxicity, something which is associated with anxiety and depression. He concludes that clinicians should exercise prudent judgment in deciding whether or not to treat patients with advanced cancer due to trials testing beyond third-line therapy not reflecting real-world patients and financial toxicity being a significant issue.
Read MoreTaking the con position in a point-counterpoint debate, Alan H. Bryce, MD, Medical Director of the Genomic Oncology Clinic at Mayo Clinic Arizona in Scottsdale, makes an argument against treating metastatic castration-resistant prostate cancer (mCRPC) based on the differences between trial and real-world populations, and the challenges of extreme treatments. Dr. Bryce cites quality of life post-treatment, financial toxicity, and patient-centric treatment as cons of mCRPC treatment. He shows a graph of mCRPC treatment management in clinical practice and states that the rapid drop off after first-line therapy could be caused by patient drop outs instead of undertreatment. Dr. Bryce discusses the mCRPC treatment process in detail, focusing on how after the first line of therapy, treatment options become much more extreme and mostly consist of chemo, and most patients only have about a year left to live if they are beyond second-line treatment. He uses a case study of a 73-year-old patient to show how real-world patients can differ from selected trial patients due to how patient selection leads to optimized outcomes. Dr. Bryce reviews data showing that 20% of patients report financial toxicity, something which is associated with anxiety and depression. He concludes that clinicians should exercise prudent judgment in deciding whether or not to treat patients with advanced cancer due to trials testing beyond third-line therapy not reflecting real-world patients and financial toxicity being a significant issue.
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