Abstract / Summary
Abstract Background: Radical prostatectomy (RP) remains a cornerstone treatment for patients with localized prostate cancer. Previous studies have suggested that prior RP may impact clonal evolution of metastatic disease and response to subsequent systemic therapies. In this study, we sought to investigate whether a history of prior RP is associated with treatment response and survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with ¹⁷⁷Lu-PSMA. Methods: In a single-institution retrospective study, we identified 260 patients who underwent 177Lu-PSMA for mCRPC. Patients were categorized based on the history of prior PR into two groups; Group A (n=147) included patients with prior PR, and Group B (n=113) included patients with intact prostate. The primary outcome was prostate-specific antigen (PSA) response, defined as a ≥50% decline from baseline (PSA50). Overall survival (OS) was evaluated as a secondary outcome. Univariable and multivariable regression analyses were performed to identify factors associated with PSA50 and OS. Results : Among 260 patients, PSA50 was achieved in 55.1% of patients with prior RP compared with 34.5% of those with an intact prostate. On multivariable logistic regression, prior RP remained independently associated with greater odds of achieving PSA50 (OR 2.1, 95% CI 1.09–4.1; p=0.03), whereas de novo metastatic disease was not independently associated with PSA50 (OR 0.97, 95% CI 0.44–2.15; p=0.9). Prior RP was also associated with improved OS on multivariable Cox regression (HR 0.60, 95% CI 0.4–0.8; p=0.008). Conclusion: In our experience, Prior RP was independently associated with improved PSA response and OS among patients with mCRPC treated with ¹⁷⁷Lu-PSMA. These findings suggest that prior treatment of the primary tumor may be associated with subsequent response to PSMA-targeted radioligand therapy, although the underlying mechanisms and potential influence of treatment selection and disease biology warrant further investigation.