A. Edward Yen, MD

A. Edward Yen, MD

Baylor College of Medicine

Houston, Texas

A. Edward Yen, MD, is an assistant professor of medicine in the hematology and oncology section at Baylor College of Medicine in Houston, Texas. He is a practicing genitourinary medical oncologist at the Dan L Duncan Comprehensive Cancer Center and the Bladder Cancer Center at Baylor He is also affiliated with Baylor St. Luke’s Medical Center and the Houston VA Medical Center Hospital. Dr. Yen earned his MD from Baylor College of Medicine. His research on androgen receptors in hormone-dependent and castration-resistant prostate cancer has been published in Pharmacology & Therapeutics. His professional interests include prostate and genitourinary cancers.

Disclosures:

Talks by A. Edward Yen, MD

Metastatic Prostate Cancer: Can Urologists Work Alongside Medical Oncologists in Advanced Disease?

A. Edward Yen, MD, discusses the importance of collaborating with medical oncologists when using hormone-directed therapy to treat metastatic prostate cancer. He begins by illustrating changes in treatment approach, using a case study to contrast past treatment algorithms with modern treatment approaches.

Dr. Yen presents a treatment algorithm from the early 2000s, calling attention to the isolation of “urologist” versus “oncologist” options in patient treatment and the impact of those isolated treatment approaches on overall survival. Dr. Yen contrasts this approach with modern agents and therapies which require collaboration between urologists, medical oncologists, and other medical disciplines.

Dr. Yen then addresses practical challenges associated with increased multidisciplinary collaboration, including keeping up with rapid advancements, managing treatment toxicities, and sequencing and selecting treatment.

Dr. Yen concludes by presenting a model of collaboration used by his practice which integrates urology, medical oncology, radiation oncology, nuclear medicine, pathology, interventional radiology, palliative/supportive care, genetics, nutrition and dietetics, psychology, and social work in treatment. He notes that the involvement of these specialties in the treatment of advanced prostate cancer leads to comprehensive evaluations, tailored treatment plans, and better outcomes for patients.

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Neoadjuvant vs. Adjuvant vs. None – “Perioperative Therapy”

A. Edward Yen, MD, Assistant Professor of Medicine in the Hematology and Oncology Section at Baylor College of Medicine in Houston, Texas, summarizes research on perioperative therapies for bladder cancer and how they compare to each other. He begins with an overview of the current standard of care for muscle-invasive bladder cancer (MIBC), citing a Swiss study showing that after radical cystectomy there is still a problem of incurable disease relapse through overall survival rates below 63%, and another study showing that neoadjuvant cisplatin-based chemotherapy (NAC) combinations improve survival for MIBC by 5-8%. Dr. Yen then overviews NAC, highlighting the VESPER trial that compared cisplatin-gemcitabine (GC) and dose-dense MVAC (ddMVAC) in the perioperative MIBC setting and found that more patients were able to follow through with NAC than adjuvant chemotherapy (AC) by 21%. He discusses multiple immunotherapy trials that together show that patient responses seem better with chemo-immunotherapy than they do with immunotherapy alone. Dr. Yen then reviews the CheckMate-274 trial that found that adjuvant nivolumab treatment-related adverse effects were tolerable due to a 7% rate of being severe enough to end treatment vs. a 1.4% rate in the placebo arm. He also summarizes the IMvigor trial, which did not meet its primary endpoint of disease-free survival but found that positive ctDNA patients had an improvement from atezolizumab that was not seen in other patients. Dr. Yen concludes that GC and ddMVAC remain important perioperative chemotherapy regimens, that neoadjuvant and adjuvant therapies have situational uses, and more research will be key to refining these treatments further.

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Local Therapy – Managing Locoregional (LR) Complications in Metastatic Prostate Cancer

A. Edward Yen, MD, Assistant Professor of Medicine in the Hematology and Oncology Section at Baylor College of Medicine in Houston, Texas, explains the use of local therapy, meaning treatment to the primary prostate, in patients with metastatic prostate cancer. He outlines locoregional complications in these patients, calling it a significant problem and pointing out that these complications may threaten further therapy and survival. He predicts this problem may worsen due to the increasing incidence of metastatic prostate cancer and the fact that more patients are living longer with metastatic disease. Dr. Yen poses the question, “Is there a role for local therapy beyond palliation?” He describes and cites outcomes from a selection of retrospective studies that support a survival benefit associated with local therapy in metastatic prostate cancer patients. Dr. Yen then turns to the HORRAD study, whereby patients with metastatic castration-sensitive prostate cancer (mCSPC) were given androgen deprivation therapy (ADT) with or without prostate radiation. Dr. Yen analyzes the data on the study’s endpoints, overall survival (OS) and time to prostate-specific antigen (PSA) progression, which conclude there was no difference in OS but a potential benefit in those with fewer than five bone metastases and that there was a significant prolonging of the median time to PSA progression with the addition of radiation therapy (RT). Dr. Yen then describes the multi-arm, multi-stage STAMPEDE trial that looked at systemic therapy with or without RT in patients with mCSPC. The trial concluded there was no difference in OS but there was improvement in failure-free survival (FFS) for patients receiving RT. Dr. Yen points out that in the prespecified subgroup analysis, local therapy was associated with OS benefit in patients with low disease burden. He then lists ongoing studies before turning to future questions regarding local therapy in patients with metastatic prostate cancer, such as those involving patient benefit and risk factors, staging and stratification, and the effects of concurrent treatment. Dr. Yen concludes that patients receiving local therapy should be included within the context of one of the many clinical trials taking place.

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Clinical Case Discussion: Metastatic Prostate Cancer and Evidence for More Precision Therapy

A. Edward Yen, MD, Assistant Professor of Medicine in the Hematology and Oncology Section at Baylor College of Medicine, introduces a metastatic prostate cancer case, and through it explores and reviews treatment options. He discusses homologous recombination and the role that it plays in DNA repair pathways, noting that 25% of patients with advanced prostate cancer have deleterious mutations in DNA damage repair genes which lead to an increased risk of prostate cancer and chance of having nodal and/or distant metastases. Dr. Yen then reviews the TRITON2 study on rucaparib in mCRPC patients with homologous recombination deficiency and the PROfound study on olaparib in mCRPC patients with homologous recombination repair alterations, both of which found a far greater response to treatment in the cohorts with the target mutations. Next, Dr. Yen discusses PARP inhibitors and their side effects, such as fatigue, nausea, pulmonary embolism, anemia, and others. Through his exploration of treatment options, Dr. Yen concludes that next-line chemotherapy is the best option for the patient given the visceral progression of their disease.

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Immunotherapy For Muscle Invasive Bladder Cancer

A. Edward Yen, MD, Assistant Professor of Medicine in the Hematology and Oncology Section at Baylor College of Medicine in Houston, Texas, discusses the findings of recent immunotherapy trials for muscle invasive bladder cancer (MIBC). He explains that cisplatin-based neoadjuvant chemotherapy combinations are the current standard of care for MIBC and can provide a significant overall survival benefit, but 40 to 50% of patients are not eligible for cisplatin to begin with, and only 20% of those eligible patients actually receive cisplatin, which suggests that there are major therapeutic gaps that immunotherapies could potentially fill. Dr. Yen goes into depth on the findings of the phase II PURE-01 study of pembrolizumab, the phase II ABACUS study of atezolizumab, and the phase I NABUCCO study of nivolumab/ipilimumab, observing that all three therapies produced good responses and appeared to be correlated to different biomarkers from one another. He concludes by predicting that neoadjuvant immunotherapy will become standard of care for cisplatin-ineligible patients, but he also stresses that future studies should include higher-risk patients and should focus on predictive biomarkers.

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