Correlation of Tumor Absorbed Dose with Progression-Free Survival in Metastatic Castration-Resistant Prostate Cancer Treated with ¹⁷⁷ Lu-PSMA

Today's common practice of empiric activity prescription in radiopharmaceutical therapy is inconsistent with the modern philosophy of personalized medicine. We investigate the radiobiologic relationship between tumor mean absorbed dose (<i>D</i> _mean) and progression-free survival (PFS) in ¹⁷⁷Lu-PSMA I&T therapy guided by personalized predictive dosimetry in metastatic castration-resistant prostate cancer. <b>Methods:</b> We conducted a single-center retrospective study of the first 20 patients treated with ¹⁷⁷Lu-PSMA I&T at our institution. PFS was calculated from the day a patient was assessed by a nuclear medicine physician in the clinic until treatment cessation (due to progression or toxicity) or death. <i>D</i> _mean was estimated by predictive dosimetry. Correlation with PFS was performed on the following baseline characteristics: age, Gleason score, Eastern Cooperative Oncology Group performance status, estimated glomerular filtration rate, prostate-specific antigen (PSA) doubling time, injected activity per treatment, <i>D</i> _mean and <i>D</i> _mean per gigabecquerel. <b>Results:</b> Twenty patients naïve to ¹⁷⁷Lu-PSMA were treated over a 2-y period, totaling 65 infusions. The median PSA doubling time was 1.6 mo at baseline. The median follow-up time was 8.4 mo (interquartile range [IQR], 4.6-14.5 mo). Each patient received 3 ± 1 treatments (range, 1-5), with a mean injected activity of 7.74 ± 0.66 GBq per treatment. The mean injected activity for the first treatment was 7.85 ± 0.71 GBq. The median <i>D</i> _mean for the first treatment was 23 Gy (IQR, 15-36 Gy). The median PFS was 10.6 mo for a <i>D</i> _mean of 23 Gy or greater and was 3.1 mo for a <i>D</i> _mean of less than 23 Gy (hazard ratio, 0.39; 95% CI, 0.22-0.68; <i>P</i> < 0.01). There were statistically significant correlations between PFS, PSA doubling time, and <i>D</i> _mean (<i>P</i> < 0.05). However, there was no statistically significant correlation between the injected activity per treatment versus PFS or <i>D</i> _mean (<i>P</i> > 0.05). <b>Conclusion:</b> We found a strong direct correlation between <i>D</i> _mean and PFS in patients with metastatic castration-resistant prostate cancer treated with ¹⁷⁷Lu-PSMA in a real-world setting. We identified a <i>D</i> _mean of 23 Gy as a possible threshold for significantly better PFS in our cohort with median PSA doubling time of 1.6 mo. Our findings support radiobiologically sound prescription based on the radiation absorbed dose by personalized predictive dosimetry.