Early treatment of advanced prostate cancer with radioligand therapy prolongs life

Research presented at the 2018 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) demonstrates for the first time the benefit of providing earlier lutetium-177 (¹⁷⁷Lu) prostate-specific membrane antigen (PSMA) radioligand therapy to patients with metastatic prostate cancer. Until now, this therapy has only been used in patients with end-stage disease.

The study included 224 patients with metastatic prostate cancer, who were restaged following diagnosis with gallium-68 (⁶⁸Ga)-PSMA positron emission tomography/computed tomography (PET/CT)—the diagnostic partner of ¹⁷⁷Lu-PSMA radioligand therapy (PRLT); the two form a theranostic nuclear medicine pairing. Theranostics refers to the combination of a predictive biomarker, in this case PSMA, identified through diagnostic imaging using radiolabeled ligands (which lock onto the specific cancer cell receptor/biomarker), with precise therapy targeted on the now-identified cancer cells. The cancer cells are destroyed, while healthy cells are unharmed—minimizing side effects and improving quality of life for patients.

The patients were grouped according to previous therapies, which included surgery, chemotherapy and external beam radiation therapy. Serum prostate specific antigen (PSA) levels were monitored before and after therapy with ¹⁷⁷Lu PRLT.

Study results showed a reduction in PSA level in 70 percent of the patients treated with ¹⁷⁷Lu PRLT, and 54 percent had their PSA decline by more than 50 percent. The median overall survival in all patients was 27 months. First-line PRLT was associated with the longest survival (all 18 patients alive at 55 months). Patients previously treated with chemotherapy had a significantly shorter survival (median of 19 months). Survival was also shorter in patients with previous radium-223 (²²³Ra) treatment (17 months). On the other hand, prior surgical or radiation treatment of the primary tumor had no significant effect on overall survival. Patients demonstrating a PSA decline of more than 50 percent after at least two PRLT cycles, lived significantly longer (38 months). Additional treatment with newer antiandrogen agents Abiraterone or Enzalutamide in combination with ¹⁷⁷Lu PRLT also prolonged survival.

"Our study demonstrates a potential survival benefit and superior response after early initiation of ¹⁷⁷Lu-PSMA radioligand therapy," explains Harshad R. Kulkarni, MD, of the THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging, Zentralklinik Bad Berka in Bad Berka Germany. "PRLT was safe with no or minimal side effects. These results are, therefore, likely to have a significant impact on patients' lives—maintaining their quality of life for longer."

He points out, "This approach of precision oncology uses the concept of theranostics—i.e., we see what we treat, and we treat what we see. ¹⁷⁷Lu-PRLT patients were selected and followed-up with ⁶⁸Ga-PSMA PET/CT, using the same ligand for molecular imaging and molecular radiotherapy."

Kulkarni adds, "These findings will help to determine the right place of ¹⁷⁷Lu-PSMA radioligand therapy in the treatment of metastatic prostate cancer—for example before chemotherapy—and serve as a starting point for a prospective randomized controlled clinical trial."