Topic: Radiopharmaceuticals

Convergent Therapeutics: Next-Generation Targeted Radiotherapies

by Philip Kantoff, MD | Jun 2024

Philip Kantoff, MD, explores the advancements in targeted radiotherapies, emphasizing their potential to revolutionize prostate cancer treatment. He introduces next-generation targeted radiotherapies, such as radioligand therapy, which utilize molecules designed to bind specifically to cancer cell markers, delivering lethal doses of radiation directly to the tumor cells. This approach minimizes damage to surrounding healthy tissues, a limitation of traditional radiotherapy.

Dr. Kantoff highlights convergent therapeutics, which combines targeted radiotherapy with other treatment modalities, including immunotherapy and conventional chemotherapy. Kantoff also addresses the challenges of implementing these advanced therapies in clinical practice.

PSMA Radiopharmaceuticals: Update 2023

by A. Oliver Sartor, MD | Oct 2023

A. Oliver Sartor, MD of Tulane University School of Medicine, presents on the use of prostate-specific membrane antigen (PSMA) radiopharmaceuticals in the treatment of prostate cancer in 2023. He provides a comprehensive overview of recent advancements, clinical applications, and future directions for PSMA-targeted therapies. He discusses the latest developments in PSMA-based imaging, highlighting the efficacy of PSMA PET/CT scans in detecting prostate cancer metastases with high sensitivity and specificity. Dr. Sartor emphasizes that these imaging techniques have revolutionized the staging and restaging of prostate cancer, enabling more accurate assessment of disease spread and guiding treatment decisions.

Dr. Sartor also covers therapeutic applications of PSMA radiopharmaceuticals, focusing on PSMA-targeted radioligand therapy (RLT). He presents data from recent clinical trials demonstrating the efficacy of PSMA RLT with agents such as lutetium-177 (Lu-177) PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC).

In conclusion, Dr. Sartor highlights the transformative impact of PSMA radiopharmaceuticals on the management of prostate cancer, underscoring the potential of PSMA-targeted radiopharmaceuticals to significantly enhance the detection and treatment of prostate cancer, offering new hope for patients with advanced disease.

Therapeutic Radiopharmaceuticals in Prostate Cancer: What the Urologist Needs to Know

by Phillip J. Koo, MD | Jun 2023

Phillip J. Koo, MD analyzes therapeutic radiopharmaceuticals and their evolving role in the management of prostate cancer.

Radium-223 Trial Updates

by Daniel P. Petrylak, MD | Jul 2021

Daniel P. Petrylak, MD, Director of Genitourinary Oncology, Professor of Medicine and Urology, Co-Leader of Cancer Signaling Networks, and Co-Director of the Signal Transduction Program at Yale University Cancer Center in New Haven, Connecticut, launches his talk with some background on radium-223 before reviewing the ALpharadin in SYMptomatic Prostate CAncer (ALSYMPCA) trial, including study design, patient demographics, and baseline characteristics. He presents an updated analysis of overall survival (OS) which showed a benefit of 3.6 months compared with a placebo. Dr. Petrylak posits that it makes sense to combine radiation and immunotherapy because of potential synergism, citing the abscopal effect. He then refers to a trial, A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer, addressing the three arms of the trial and presenting survival data, including a waterfall plot demonstrating prostate-specific antigen (PSA) and a very modest objective response rate. Dr. Petrylak discusses the evaluation of the abscopal effect, with trial data not showing PDL1 expression increasing after radium-223; in terms of the abscopal effect, Dr. Petrylak concludes, “it’s just not there.” He further concludes that the trial findings were disappointing. Dr. Petrylak then turns his focus to research on radium-223 with abiraterone/prednisone that found increased patient bone fractures. This finding led to an urgent safety letter being issued, mandating the use of bone-protective agent (BPAs) for at least six weeks before the first injection of radium-223 to reduce fractures. Dr. Petrylak cites data from the EORTC 1333/PEACE III trial which confirms that risk of fractures was well controlled when patients with metastatic castration-resistant prostate cancer (mCRPC) received BPAs, emphasizing the importance of compliance with the BSA recommendations. Dr. Petrylak moves on to cite a study examining radium-223 with chemotherapy (docetaxel) showing significant PSA declines. This research is now part of the DORA trial, which is still recruiting patients nationally. Dr. Petrylak addresses radium-223 dosing, citing investigational trials involving higher doses of radium-223 and extended dosing cycles. He concludes that data support the current regimen of six cycles of radium-223 at the standard dose as the optimal regimen in mCRPC. Dr. Petrylak concludes his discussion by emphasizing that combination trials with docetaxel are ongoing.

Metastasis-Directed Therapy: Radiation Oncology Updates and Perspective

by Steven E. Finkelstein, MD, FACRO | Oct 2020

Steven E. Finkelstein, MD, FACRO, a radiation oncologist with Florida Cancer Affiliates in Panama City, Florida, discusses metastasis-directed therapy (MDT) as a potential treatment option for oligometastatic prostate cancer. He reviews typical management of metastatic cancer and describes how MDT can minimize the toxicity of systemic therapy, then addresses future treatment options with stereotactic ablative radiotherapy (SABR). Radiation and other local therapies are used for palliation of metastases but can also alter the course of tumor development. Dr. Finkelstein explains that MDT can be particularly beneficial in oligometastatic prostate cancer if the metastases are at a point where both the primary tumor and metastases can be treated together and likely cured. Lastly, he concludes that MDT via SABR could be employed concurrently with other treatments such as androgen deprivation therapy (ADT), chemotherapies, and radiopharmaceuticals, and that further research is necessary.

Radiation Therapy: What’s New for Localized Disease

by Christina E. Henson, MD | Mar 2020

Christina E. Henson, MD, describes how recent trial-based research has established new standards in prostate cancer radiotherapy. She discusses several modes of therapy, including hypofractionation, metastasis-directed therapy for treating oligometastatic disease, and pelvic nodal irradiation, noting that research has shown them to be effective treatments in a variety of disease states. Ultra-hypofractionation has been proven to have an increased therapeutic ratio compared to other methods, as well as a 5-year failure-free survival of 84% across all trials. Elective nodal radiation up to L4 or higher is now recommended to maximize treatment outcomes. Metastasis-directed therapy has been proven to help patients even with limited disease burden and should be viewed as an option in these cases, though it is not always successful.

M0 CRPC: Treatment Options and Emerging Concepts

by Alicia K. Morgans, MD, MPH | Mar 2020

Alicia K. Morgans, MD, MPH, Associate Professor of Medicine in Hematology and Oncology at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, discusses the use of androgen receptor antagonists in treating patients with non-metastatic (M0) castrate-resistant prostate cancer (CRPC). She goes on to discuss how before these three pivotal trials, treatment for patients with M0 CRPC remained a bit of a mystery. However, the results of these trials demonstrated treating men with these agents who had a PSA doubling time less than ten months significantly improved their metastasis-free survival compared to men in the control arm.

MRI First: The Role of MRI in Biopsy Naïve Patients

by Montu J. Patel, MD | Feb 2020

Monju J. Patel, MD, discusses how variation in mpMRI image quality and radiologist interpretation and experience, as well as technicalities of the PIRADS-2 scoring system, can significantly impact radiologists’ ability to detect lesions suspicious for prostate cancer. He goes on to present several case studies on how to utilize mpMRI’s strong specificity to evaluate extraprostatic extension and anterior transition zone tumors, and how to use mpMRI to evaluate the entire pelvis for possible metastatic disease. Finally, Dr. Patel considers the detection pitfalls of mpMRI, such as differentiating benign anatomy versus a malignancy, abnormalities that exist in the central zone, and how to identify diffuse, infiltrative carcinoma.

Exosomal Liquid Biopsy in Prostate Cancer: Role in Prostate Biopsy Decision-Making

by Judd W. Moul, MD | Feb 2020

Judd Moul, MD, Professor of Surgery and Anesthesiology as well as the James H. Semans, MD, Distinguished Professor of Urologic Surgery at Duke University School of Medicine, discusses the ExoDx Prostate Intelliscore (EPI), a urine-based liquid biopsy test with high negative predictive value (NPV) that may be a useful prostate cancer (PCa) diagnostic tool for primary care providers (PCPs). He emphasizes EPI’s relative ease of use, noting that it is necessary to have simple screening procedures in order to take the burden off of over-stretched urologists.

PSMA-11 PET: Atypical Paths to FDA Approval and Academic NDAs

by Thomas Hope, MD | Feb 2020

Thomas Hope, MD, Assistant Professor in Residence in Abdominal Imaging and Nuclear Medicine in the Department of Radiology at the University of California, San Francisco, explains how an academic institution successfully submits a new drug application (NDA) to the US Food and Drug Administration (FDA), using the NDA for prostate-specific membrane antigen (PSMA) 11 as an example. He notes the limitations that academia has in this area, and recommends that, going forward, institutions design imaging studies so that they report usable detection rates and have blinded readers.

Current and Emerging Role of Radiogenomics

by John Feller, MD | Feb 2020

John Feller, MD, Founding Partner and Medical Director at Desert Medical Imaging, gives an overview of radiogenomics’ current and possible future role in prostate cancer care. He notes the recent promising results of multiparametric MRI (mpMRI) from trials, which have shown that using mpMRI before transrectal ultrasound-guided (TRUS) biopsy can decrease the number of unnecessary biopsies, limit detection of insignificant cancer, and improve detection of significant cancer. These have influenced the updated 2019 National Comprehensive Cancer Network (NCCN) Guidelines for prostate cancer. Dr. Feller further discusses other biomarkers for risk stratification and promising research on radiogenomics in the setting of focal therapy.

Combining SBRT and Brachytherapy in Higher Risk Prostate Cancer

by Michael J. Zelefsky, MD | Sep 2019

Michael J. Zelefsky, MD, argues that combining stereotactic body radiation therapy (SBRT) with low-dose rate brachytherapy can help to reduce the morbidities of combined-modality radiotherapy. He also emphasizes the need to address the issue of toxicity with careful patient selection, treatment planning, and adherence to tight dose constraints.

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