After the VISION trial showed that therapy with the radioligand, 177Lu-PSMA, was effective in patients with advanced metastatic castration-resistant prostate cancer (mCRPC), researchers, led by Masatoshi Hotta, MD, assessed 177Lu-PSMA treatment outcomes in patients who would have been a screen failure (SF) under the VISION trial’s PSMA-PET/CT inclusion criteria. The findings were presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.
According to Dr. Hotta, SF patients attained worse outcomes compared to VISION-eligible patients. This finding opposed the position of some investigators who, noting the low SF rate in the VISION study, suggested that eligibility screening prior to 177Lu-PSMA treatment is unnecessary.
The final analysis included 301 patients who had been treated with one or more cycles of 177Lu-PSMA. The two criteria for SF from the VITAL trial were: an absence of metastatic lesions plus low/no PSMA expression, and a presence of one or more metastatic lesions measurable by CT. The cohort was largely composed of eligible patients (272/301), and a smaller group of SF patients (29/301). Compared to VISION-eligible patients, SF patients had a worse prostate-specific antigen >50% response rate (PSA50RR) (p = 0.005), overall PSARR (p = 0.003), median PSA progression-free survival (p = 0.023), and a typically lower median overall survival (p = 0.16).
Dr. Hotta and colleagues supported the continued use of PSMA-PET eligibility screening for 177Lu-PSMA therapy, though they noted that “refinements in patient selection for 177Lu-PSMA are needed to optimize patient outcomes.”
Ultimately, while the authors acknowledged that optimal treatment plans for negative or low PSMA-expressing lesions were underexplored, they suggested that “combining 177Lu-PSMA therapy with external-beam [radiation therapy (RT)] and/or with other systemic therapy may be an effective therapeutic approach.”
