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Advances in mCRPC

CE / CME

Advances in Metastatic Castration-Resistant Prostate Cancer: Biomarker-Driven Treatment Strategies and Emerging Therapeutic Approaches

ABIM MOC: maximum of 0.50 Medical Knowledge MOC point

Physicians: Maximum of 0.50 AMA PRA Category 1 Credit™

Released: July 20, 2026

Expiration: January 19, 2027

Neal D. Shore
Neal D. Shore, MD, FACS
CME/CE Information

Activity

Progress
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Course Completed

Next-Generation Immunotherapy

Historically, prostate cancer has been considered a relatively "cold" tumor. Although sipuleucel-T, a dendritic cell therapy that activates antigen-presenting cells, is approved in the United States, several promising immunotherapeutic approaches are now under investigation.

One such approach involves bispecific T-cell engagers. Xaluritamig is a potent STEAP1-targeted bispecific T-cell engager that has demonstrated encouraging activity in advanced prostate cancer. In parallel, DLL3-directed therapies are being investigated in patients with neuroendocrine prostate cancer, where DLL3 is often highly expressed and may represent an important therapeutic target. Tarlatamab has demonstrated the clinical potential of DLL3-targeted therapy in small-cell lung cancer, and DLL3-directed approaches may also be relevant for neuroendocrine prostate cancer.

Bispecific antibodies work by engaging T-cells while simultaneously targeting specific tumor antigens, such as STEAP1, KLK2, or DLL3, thereby directing an immune response against cancer cells.

There is also interest in CAR T-cell therapies. Although CAR T-cell therapy has achieved tremendous success in hematologic malignancies, including leukemias and lymphomas, advances in solid tumors have been more limited. Nonetheless, there remains significant enthusiasm for determining whether CAR T-cell therapy can be effectively leveraged in patients with prostate cancer.

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Evolving Era of Cell Surface Targeting: Under Investigation

As we continue to learn more about targets such as PSMA, DLL3, TROP2, and B7-H3, additional therapeutic opportunities are emerging.  Multiple platforms are being evaluated, including radioligand therapies, T-cell engagers, CAR T-cell therapies, and antibody–drug conjugates.

This is a very exciting and encouraging time for research investigators and, of most importance, for our patients. Although we still face a major unmet need in patients with resistant disease, our goal is to provide life-prolonging therapies that are well targeted and do not negatively affect quality of life. We recognize that toxicities will occur, but we also want to ensure that they can be managed appropriately. All this falls under the rubric of multidisciplinary collaboration and collegiality.

Numerous investigational agents targeting cell surface proteins are on the horizon for patients with mCRPC. These agents use different mechanisms of action, including antibody–drug conjugates, CAR T-cell therapy, bispecific T-cell engagers, and radioligands.

Participation in clinical trials is considered an SoC. Our colleagues need to remain aware of opportunities through ClinicalTrials.gov and other resources so that eligible patients can be enrolled in these studies. Clinical trials are how we change clinical care.

For HCPs treating advanced prostate cancer, it is important to understand trial designs, mechanisms of action, potential toxicities, administration logistics, patient preferences, treatment goals, and access barriers, including financial toxicity.

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Takeaway

We want to optimize treatment options for patients with prostate cancer through life-prolonging therapies. Optimization may involve either treatment intensification or deintensification. It is important that patients are aware of all available options. This is shared decision-making and reflects a move away from a paternalistic approach in which we simply tell patients what they are going to do. Instead, we should explain options to patients and their family members so they can be part of the decision-making process.

Multidisciplinary management will vary by practice setting, geography, access to imaging and radiopharmaceuticals, trial availability, and local collaboration across urology, medical oncology, radiation oncology, nuclear medicine, pathology, nursing, pharmacy, genetics, and supportive care.

Genetic and IHC testing are now essential. There is no longer a question of whether to consider them; they must be incorporated to optimize patient access to both approved therapies and clinical trial opportunities.

The treatment landscape is expanding rapidly and becoming increasingly complex. As a result, collegial collaboration is critical. Fortunately for the field and the landscape, we are likely to see many additional regulatory approvals in the coming years.

Do you plan to make any changes in your clinical practice based on what you learned in today’s program?

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