The emerging role of prostate-specific membrane antigen–targeted radioligand therapy in metastatic hormone-sensitive prostate cancer

Sep 23, 2026

Uploaded by Ben

Metastatic hormone-sensitive prostate cancer (mHSPC) treatment has increasingly shifted toward combination strategies that improve survival versus androgen deprivation therapy (ADT) alone. Yet many eligible patients still receive ADT monotherapy, and even approved doublet regimens can yield suboptimal outcomes. The benefit of adding docetaxel to androgen receptor pathway inhibitor (ARPI)/ADT is unclear, especially in low-volume disease, while chemotherapy tolerability remains a key limitation. This review evaluates PSMA-targeted radioligand therapy (RLT) as a non-chemotherapeutic combination approach, building on demonstrated survival gains in metastatic castration-resistant prostate cancer, and outlines challenges for integration to support informed clinical care.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Implications for practice

Introduction

Treatment landscape and unmet needs

Potential role of PSMA-targeted radioligand therapy (RLT)

Barriers and solutions for integration into mHSPC care

The Oncologist, 2026, 31, oyag173 [https://doi.org/10.1093/oncolo/oyag173](https://doi.org/10.1093/oncolo/oyag173) [Published: May 11](Published: May 11), 2026 Review Article The emerging role of prostate-specific membrane antigen–targeted radioligand therapy in metastatic hormone-sensitive prostate cancer Philipose Mulugeta*,1, , Tanya Dorff2, , Jason Hafron3, Mai Anh Huynh4,5,6, Alicia K. Morgans7, Ashley E. Ross8, Rana R. McKay9 1 Division of Nuclear Medicine Imaging and Therapy, Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, United States 2City of Hope Comprehensive Cancer Center, Duarte, CA 91010, United States 3 Michigan Institute of Urology, Troy, MI 48084, United States 4 Massachusetts General Brigham Cancer Institute, Boston, MA 02115, United States 5 Dana-Farber Cancer Institute, Boston, MA 02215, United States 6 Department of Radiation Oncology, Harvard Medical School, Boston, MA 02115, United States 7 Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, United States 8 Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States 9 Department of Medicine, Urology, and Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA 92093, United States *Corresponding author: Philipose Mulugeta, MD, Division of Nuclear Medicine Imaging and Therapy, Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA ([philipose.mulugeta@pennmedicine.upenn.edu](philipose.mulugeta@pennmedicine.upenn.edu)) . Abstract The treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has evolved in recent years towards combination therapy, enhancing survival outcomes when compared with androgen deprivation therapy (ADT) alone. However, many patients who are eligible for combination therapy are still receiving ADT monotherapy, and a significant proportion of those treated with doublet combinations still experience suboptimal outcomes. Furthermore, the value of adding docetaxel to an androgen receptor pathway inhibitor (ARPI)/ADT doublet in mHSPC has not been delineated, particularly in patients with low-volume disease, and chemotherapy toxicity and tolerability remain a major concern for patients. This review addresses the significant unmet need for additional or novel treatment strategies for mHSPC, utilizing prostate-specific membrane antigen (PSMA)–targeted radioligand therapy (RLT) in a combination regimen that uses a non-chemotherapeutic approach for the treatment of mHSPC. PSMA-targeted RLT has been shown to improve survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with ARPIs +/ − taxanes and is now under evaluation for the treatment of mHSPC, given its demonstrated success in the mCRPC space. Thus, continued education on RLT and its use for patients with mHSPC is important to optimize patient care. This review provides a brief outline of the mHSPC treatment landscape, focusing on the challenges and unique considerations faced by healthcare professionals when treating these patients. We also evaluate the potential role of RLT in surmounting these challenges, discussing potential barriers and solutions to its integration as a treatment for mHSPC. Key words: prostate; prostatic neoplasms; castration-resistant; delivery of health care Implications for practice This review discusses the challenges and unique considerations faced by healthcare professionals when treating patients with metastatic hormone-sensitive prostate cancer, with an emphasis on the potential role of prostate-specific membrane antigen– targeted radioligand therapy in optimizing clinical outcomes. Received: June 2, 2025. Accepted: April 28, 2026 © The Author(s) 2026. Published by Oxford University Press. This is an Open Access article distributed under the t

FAQs

Why is combination therapy important in metastatic hormone-sensitive prostate cancer (mHSPC)?

Combination therapy improves survival compared with ADT alone. However, a gap remains because many patients still receive ADT monotherapy, and doublet regimens can still lead to less-than-optimal results.

What uncertainty remains about adding docetaxel in the mHSPC setting?

The value of adding docetaxel to an ARPI/ADT doublet has not been clearly delineated, particularly for patients with low-volume disease, and chemotherapy toxicity and tolerability are major concerns.

How does PSMA-targeted radioligand therapy (RLT) relate to treatment of mHSPC?

RLT has shown survival improvements in metastatic castration-resistant prostate cancer previously treated with ARPIs (+/− taxanes). It is now being evaluated in mHSPC as part of a combination regimen that uses a non-chemotherapeutic approach.

Sep 23, 2026

Uploaded by Ben