Theranostics in prostate cancer management: Current strategies and real-world data

Earlier use of lutetium-177 (¹⁷⁷Lu) prostate-specific membrane antigen (PSMA)–radioligand therapy (RLT) in combination with chemotherapy is shaping the future of prostate cancer management, according to Dr Yu-Yi Huang of the Department of Nuclear Medicine, Koo-Foundation Sun Yat-Sen Cancer Center (SYSCC), Taiwan, at Uro-Oncology Asia 2025.

Theranostics in prostate cancer management entails diagnosis using, for example, gallium-68 (⁶⁸Ga)–labelled PSMA-11 (⁶⁸Ga-PSMA-11) PET-CT imaging followed by treatment with ¹⁷⁷Lu-PSMA–RLT. “Optimal timing of PSMA-RLT use in prostate cancer patients is very important,” stressed Huang.

¹⁷⁷Lu-PSMA-RLT is currently recommended by the joint European Association of Nuclear Medicine (EANM)/Society of Nuclear Medicine and Molecular Imaging (SNMMI) guideline for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who:

(1) progressed on ≥1 androgen-receptor pathway inhibitor (ARPI; eg, enzalutamide or abiraterone) and ≥1 taxane regimen and are unfit for or refuse a second taxane regimen; or

(2) progressed on ≥1 ARPI and docetaxel, but are still possible candidates for cabazitaxel; or

(3) progressed on ≥1 ARPI but are not suitable for chemotherapy. [Eur J Nuclear Med Mol Imaging 2023;50:2830-2845]

“Recently, ¹⁷⁷Lu-PSMA–RLT has been propelled from third to second line in the mCRPC treatment pathway as an effective alternative treatment for taxane-naïve mCRPC, following favourable efficacy and safety results from the phase III PSMAfore trial,” said Huang. [Lancet 2024;404:1227-1239]

At SYSCC, 20 patients (age range, 55–91 years; bone metastasis, 90 percent; taxane-naïve, 61 percent; treated with one ARPI, 100 percent; treated with two ARPIs, 33 percent) had been treated with ¹⁷⁷Lu-PSMA-617 between September 2022 and June 2024. “Of these patients, 18 had received one to six cycles of treatment, and treatment was ongoing for two,” reported Huang. “Six treated patients are still alive [average survival, about 537 days], while 12 have passed away [survival, 17–635 days].”

“For prostate-specific antigen [PSA] response [best, whether seen during or after treatment, vs before], 61 percent of patients had ≥50 percent reduction in PSA levels. Response was durable, with 50 percent of the patients maintaining ≥50 percent reduction in PSA levels after the last cycle vs before treatment, and better response was observed in taxane-naïve patients,” Huang continued.

“However, a very high proportion [50 percent] of patients experienced grade 3/4 adverse events [AEs], which were mostly haematologic [thrombocytopenia and anaemia],” noted Huang. “This real-world observation is concerning and unexpected as it is very different from results reported in clinical trials.”

“After we discovered, through a deep learning–based artificial intelligence model, the possible correlation of higher bone tumour volume with higher risk and occurrence of severe [≥grade 3] AEs, we immediately implemented dose reduction starting from the first cycle of treatment for patients with high bone tumour volume, or adjustment of the interval between different cycles based on haematologic responses. With this strategy, we saw a decrease in grade 3/4 AEs,” said Huang.