Precision Oncology with 177 Lu-PSMA-617 Radionuclide Therapy in Elderly Patients with Metastatic Castration-Resistant Prostate Cancer

Abstract

Objective:

To investigate the treatment response status in elderly patients with metastatic castration-resistant prostate cancer (mCRPC) receiving ¹⁷⁷Lu-PSMA-617 radioligand therapy within a precision oncology framework, analyze the incidence, depth, and influencing factors of PSA and radiological response, and provide scientific evidence for developing individualized treatment selection and optimization strategies.

Methods:

A cross-sectional survey study was conducted, including 182 elderly patients (age ≥65 years, having completed ≥2 cycles of ¹⁷⁷Lu-PSMA-617 therapy) with prostate-specific membrane antigen (PSMA)-positive mCRPC confirmed by ⁶⁸Ga-PSMA-11 Positron emission tomography/Computed tomography (PET/CT). Standardized assessment tools, including the Functional Assessment of Cancer Therapy-Prostate (FACT-P), Brief Pain Inventory-Short Form, and Hospital Anxiety and Depression Scale, were used to evaluate treatment response, quality of life, and mental health. The Common Terminology Criteria for Adverse Events was applied to grade treatment-related toxicities. Univariate analysis was performed to screen influencing factors, and multivariate logistic regression analysis was conducted to identify independent predictors of treatment response.

Results:

The overall PSA50 response rate (≥50% PSA decline) was 63.7% (116/182). Moderate response (50%–89% PSA decline) accounted for 39.6%, and deep response (≥90% PSA decline) accounted for 24.2%. Radiological partial or complete response was achieved in 42.3% of patients. Patients in the response group showed significantly higher FACT-P total scores (115.6 ± 18.4 versus 84.2 ± 17.8, p < 0.001) and lower anxiety, depression, and pain scores compared with the nonresponse group. Multivariate analysis identified baseline hemoglobin < 100 g/L (OR = 2.19, 95% CI: 1.05–4.57), prior docetaxel exposure (OR = 2.18, 95% CI: 1.07–4.44), high tumor burden ≥ 10 lesions (OR = 2.35, 95% CI: 1.18–4.67), PSMA SUVmax < 12 (OR = 2.39, 95% CI: 1.11–5.14), and baseline alkaline phosphatase (ALP) > 200 U/L (OR = 2.13, 95% CI: 1.03–4.37) as independent predictors of treatment nonresponse. PSA50 response rate showed a significant increasing trend with the number of therapy cycles administered (χ²trend = 5.214, p = 0.022).

Conclusions:

Elderly mCRPC patients undergoing ¹⁷⁷Lu-PSMA-617 radioligand therapy achieve meaningful PSA50 response rates, with baseline hemoglobin, prior docetaxel exposure, tumor burden, PSMA expression level, and ALP being independent predictors of response. Treatment response is closely associated with improved quality of life and mental health outcomes, with response rates improving with additional therapy cycles. These findings provide evidence-based guidance for precision patient selection, treatment monitoring, and individualized optimization strategies for ¹⁷⁷Lu-PSMA-617 therapy.