Early prostate-specific antigen changes and clinical outcome after ¹⁷⁷Lu-PSMA radionuclide treatment in patients with metastatic castration-resistant prostate cancer

Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer. However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes after ¹⁷⁷Lu-labeled prostate-specific membrane antigen (¹⁷⁷Lu-PSMA) radionuclide treatment in metastatic castration-resistant prostate cancer patients. Methods: Men who were treated with ¹⁷⁷Lu-PSMA under a compassionate-access program at our institution and had available PSA values at baseline and at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to 3 groups on the basis of PSA changes: response ($30% decline), progression ($25% increase), and stable (,30% decline and,25% increase). The coprimary endpoints were overall survival and imaging-based progression-free survival. The secondary endpoints were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A greater than or equal to 30% decline in PSA at 6 wk was associated with longer overall survival (median, 16.7 mo; 95% CI, 14.4–19.0) than stable PSA (median, 11.8 mo; 95% CI, 8.6–15.1) (P 5 0.007) or PSA progression (median, 6.5 mo; 95% CI, 5.2–7.8) (P, 0.001). Patients with a greater than or equal to 30% decline in PSA at 6 wk also had a lower risk of imaging-based progression than patients with stable PSA (hazard ratio, 0.60; 95% CI, 0.38–0.94) (P 5 0.02), whereas patients with PSA progression had a higher risk of imaging-based progression than patients with stable PSA (hazard ratio, 3.18; 95% CI, 1.95–5.21) (P, 0.001). The percentage changes in PSA at 6 and 12 wk were highly associated (r 5 0.90; P, 0.001). Of 31 patients who experienced early PSA progression at 6 wk, 29 (94%) showed biochemical progression at 12 wk. Overall, only 1 (3%) of 36 patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). The limitations of the study included its retrospective nature and the single-center experience. Conclusion: PSA changes at 6 wk after ¹⁷⁷Lu-PSMA initiation are an early indicator of long-term clinical outcome. Patients with PSA progression after 6 wk of treatment could benefit from a very early decision to switch treatment. PSA flare-up during ¹⁷⁷Lu-PSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of ¹⁷⁷Lu-PSMA.