Influence of dosimetry accuracy on the correlation with treatment outcome in a preliminary PSMA radiopharmaceutical therapy study.

Abstract

Despite the potential of dosimetry in optimizing personalized radiopharmaceutical therapy (RPT), its limited clinical implementation impedes the development of simplified protocols for routine adoption. However, simplifications may introduce errors in dosimetry, prompting questions about their impact on clinical practice. In this retrospective study, we analyzed data from 21 patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) who underwent multiple cycles of ¹⁷⁷Lu-PSMA-617 RPT treatment. Cumulative dosimetry of all the treatment cycles was calculated using both the standard multi-time point dosimetry (MTPD) method and the single time-point dosimetry (STPD, Hänscheid approximation) method for the same cohort. Their correlations with treatment outcome (PSA decline rate and overall survival, OS) and complication risk (anaemia grade) were investigated. The Fisher's Z-Transformed test was performed to statistically evaluate the difference between the correlations. STPD showed a non-significant difference in correlation with PSA decline rate, despite a mean percentage error (MPE) of up to 36.44% in tumor dosimetry compared to MTPD (MTPD: rho = -0.39, p < 0.001; STPD: rho = -0.46, p < 0.001; Z = 0.58, p = 0.56). Both STPD_total and MTPD_total demonstrated a significant impact on OS (STPD_total: Hazard Ratio = 1.05, p < 0.05, log-transformed MTPD_total: Hazard Ratio = 3.41, p < 0.05, log-transformed STPD_total: Hazard Ratio = 8.06, p < 0.05). Additionally, despite a MPE of up to -40.26% in bone marrow dosimetry, STPD showed a non-significant difference in correlation with anemia grade (MTPD: rho = 0.35, p < 0.001; STPD: rho = 0.40, p < 0.001; Z = -0.39, p = 0.70). The preliminary findings from a small cohort indicate that the reduced accuracy of a clinically simplified protocol may not diminish the clinical therapy outcome predictive value of dosimetry. Future thorough systematic investigations may be needed to determine the clinically acceptable level of accuracy for dosimetry.