Analysis of PSA Super-responders in a Single-Center Study of ¹⁷⁷Lu-PSMA-617 Therapy

Tzu-Hsiang Lin^1,, Ko-Han Lin^2,3,, Tzu-Hao Huang^1,3, Tzu-Chun Wei^1,3,

Hsiao-Jen Chung^1,3,, Yen-Hwa Chang^1,3, Eric Yi-Hsiu Huang^1,3

¹ Department of Urology, ² Department of Nuclear Medicine,

Taipei Veterans General Hospital;

³ Department of Urology, School of Medicine and Shu-Tien Urological Science Research Center, National Yang Ming Chiao Tung University,

Taipei, Taiwan

Purpose: ¹⁷⁷Lu-PSMA-617 is a targeted radioligand therapy that has shown significant promise in the treatment of metastatic castration-resistant prostate cancer (mCRPC). A good PSA response has been recognized as a robust early predictor of progression-free survival. This study aimed to characterize a subgroup of patients achieving a >80% PSA decline – designated as “super-responders” – and to explore potential baseline and imaging factors associated with such profound responses.

Materials and Methods: Patients with mCRPC who had previously received ARPIs, taxane-based chemotherapy, or both, and underwent at least a cycle of ¹⁷⁷Lu-PSMA-617 at Taipei Veterans General Hospital between March 2023 and March 2025 were included in the study. Patients achieving a >80% PSA reduction from baseline were classified as super-responders.

Clinical parameters collected included age, Gleason grade group, TNM staging, pre-treatment levels of PSA, ALP, LDH, several PSMA imaging-based parameters, PSA progression-free survival (PSA-PFS), and radiographic progression-free survival (r-PFS). Comparative analyses were performed to identify factors associated with PSA super-response.

Results: A total of 15 patients received at least one dose of ¹⁷⁷Lu-PSMA-617 during the study period. Among them, 67% had previously received a single taxane-based chemotherapy regimen, and 93% had undergone ARPIs therapy. The median age was 71.0 years (IQR 66.5–75), with a median follow-up duration of 5.7 months (IQR 3.0–8.1). Patients received a median of 3 treatment cycles of ¹⁷⁷Lu-PSMA-617 (IQR 2–4).

Baseline mean PSA, ALP, and LDH levels were 1327.7 ng/mL, 218.3 U/L, and 327.1 U/L, respectively. PSA responses were observed in 33% of patients, with 60% of these achieving PSA reductions of more than 80%. Super-responders had a longer median PSA-PFS (549 days vs 62.5 days) and r-PFS (549 days vs 47.5 days).

Notably, super-responders exhibited higher median PSMA PET SUVmax values (52.59 vs. 36.34) and greater liver-to-spleen uptake ratios (5.87 vs. 3.99). Additionally, none of the super-responders presented with PSMA/FDG mismatched lesions or liver/spleen (L/S) reversal—which was found in 30% and 67% of non-responders, respectively.

Absence of visceral metastases was also universal among PSA super-responders. Interestingly, the median baseline PSA levels were higher in the super-responder group (203 ng/ml vs 87.3 ng/ml).

Conclusion: 

In this single-center cohort of mCRPC patients treated with ¹⁷⁷Lu-PSMA-617, super-responders – defined by a >80% PSA decline from baseline – demonstrated distinctive clinical and imaging characteristics, including high PSMA PET SUVmax, elevated liver/spleen ratios, and absence of visceral disease. Although limited by small sample size, our findings suggest that these parameters may serve as potential indicators of exceptional biochemical response and could inform patient selection and treatment optimization in future studies.