Radioligand Therapy (RLT) is an innovative treatment modality in the field of prostate cancer, enriching the therapeutic options. With further research, the personalized application of RLT and its combination with other therapies will become an important direction for the future treatment of prostate cancer. Oncology Frontier invited Dr. Angela Jia, an expert in radiation oncology at the UH Seidman Cancer Center, to share her insights on the role and future potential of RLT and local radiotherapy in the treatment of prostate cancer.Oncology Frontier: Radioligand Therapy (RLT) is one of the developmental trends in the precision diagnosis and treatment of prostate cancer. What value do you think RLT offers to patients with prostate cancer?
Dr. Angela Jia: My name is Angela Jia, and I am a radiation oncologist at University Hospital Seidman Cancer Center at Case Western Reserve University. My primary focus is treating genitourinary cancers.Radioligand therapy is one of the newer tools in our arsenal for treating prostate cancer. It was recently approved by the FDA for use in metastatic castration-resistant prostate cancer (mCRPC) patients who have progressed on chemotherapy or an androgen receptor pathway inhibitor (ARPI). This therapy expands our treatment options significantly. Traditionally, radiation has been considered a localized treatment, while hormonal therapy and chemotherapy are systemic. However, RLT is unique because it combines both approaches. It is administered systemically, allowing it to reach the entire body, yet it specifically targets cancer cells that express the prostate-specific membrane antigen (PSMA) receptor, making it highly precise.
Oncology Frontier: Currently, the focus in the field of prostate cancer diagnosis and treatment is on 177Lu-PSMA-RLT. What impact do you think it has on current clinical practice?
Dr. Angela Jia: RLT has already transformed the treatment landscape by gaining FDA approval for use in mCRPC. The current research is heavily focused on optimizing its sequencing and combination with other therapies. We now have data supporting its safety when used in combination with PARP inhibitors, immunotherapy, and various ARPIs.
One of the key questions moving forward is adaptive dosing. At present, all patients receive a fixed dose, regardless of whether they have a few or many metastatic lesions. A trial, discussed and published recently, introduced an adaptive dosing model. In this study, all patients initially received two treatment cycles followed by an interim PSMA PET scan. Based on the PET findings, approximately 11% of patients who had a complete response did not require further treatment. Those with residual PSMA-avid disease proceeded with two additional cycles. This trial underscores the need for a more personalized approach—one that integrates patient selection, biomarkers for treatment response, and strategies to avoid overtreatment while ensuring optimal therapeutic intensity when needed.
Moreover, while much of the discussion has focused on combining RLT with systemic therapies, we must also consider how external beam radiation therapy (EBRT) fits into the treatment paradigm. Stereotactic body radiation therapy (SBRT) has been primarily studied for metastasis-directed therapy in hormone-sensitive prostate cancer. However, emerging phase II trials indicate that SBRT could also be beneficial in the mCRPC setting, particularly in oligometastatic disease (fewer than 3–5 lesions). These studies suggest that SBRT may improve progression-free survival and, in some cases, even hint at a potential overall survival benefit. Moving forward, integrating SBRT with RLT could further enhance patient outcomes.
