PSA response and survival based on metastatic site in patients with metastatic castration resistant prostate cancer (mCRPC) treated with lutetium-177-PSMA-vipivotide tetraxetan (Lu177-PVT).
Authors: Joseph David Allen, Colin P Bergstrom, Hong Song, Catiussi Hoffmann, Shann Mika Ruiz, Joanne Chien, Kaidi Moore, Divya Ahuja Parikh, Sumit Shah, Alice C. Fan, Sandy Srinivas, Andrei Iagaru, Ali Raza Khaki
Journal: Journal of Clinical Oncology (2025)

107 Background: Patients (pts) with mCRPC can have different metastatic sites with variable outcomes. Lu177-PVT is a novel treatment for mCRPC but response and outcomes in the real world are still being defined. We hypothesized that pts with lung and liver metastases (mets) would have worse outcomes (lower PSA response and shorter survival) with Lu177-PVT than those without as advanced of disease spread. Methods: This retrospective cohort study analyzed pts with mCRPC who were treated with at least one dose of Lu177-PVT. PSA50, PSA90, and overall survival were assessed for three comparisons of pts: bone only vs. other mets (including other site ± bone), lung-involved vs. lung-absent, and liver-involved vs. liver-absent. PSA50 and PSA90 were defined as achieving any reduction in PSA below 50% and 90% of baseline prior to Lu177-PVT therapy, respectively. Comparisons between groups were made using univariable logistic regression for PSA50 and PSA90 and Cox regression for OS. Results: We included 100 pts for OS analyses and 97 pts for PSA50 and PSA90 analyses treated between 03/2019 and 09/2024. Three pts were excluded from PSA analyses due to absence of baseline PSA prior to Lu177-PVT. Median age at Lu177-PVT start was 66 years, 67% white race, 45% ever smoker, median BMI was 26 kg/m 2 , 5 median previous lines of treatment, 77% received prior chemotherapy, and 4 median number of Lu-177-PVT treatments received. At time of initial Lu177-PVT, 94% had at least bone mets, 12% had LN mets, 14% had lung mets, 15% had liver mets, and 9% had other mets. Table shows results of all comparisons. Pts with only bone mets (vs those with other site ± bone) had numerically (not significant) longer OS (Table; median [m]OS 19 vs. 13 months, HR 0.88, p-value 0.70) and similar PSA50 and PSA90 rates. Pts with liver-involved (vs liver-absent) had a numerically shorter OS (mOS 15 vs. 18 months, HR 1.45 p-value 0.38) and lower (not significant) PSA90. Pts with lung-involved (vs lung-absent) had numerically shorter OS (15 vs. 18 months, HR 1.28, p-value 0.58) and lower PSA90. Conclusions: Pts with mCRPC responded to Lu177-PVT regardless of metastatic sites in our study, though liver mets had numerically lower OS. Study limited by small power and retrospective study design. Future work is needed to further dissect the interplay between Lu177-PVT response and metastatic disease sites. Results. N Median Lu177-PVT cycles received Median Overall Survival, months (95% CI) HR for OS, (95% CI) PSA50%, (95% CI) OR for PSA50, (95%CI) PSA90%, (95% CI) OR for PSA90, (95%CI) Bone only 56 5 19 (1-40) 0.88 (0.45-1.71) 58 (43-70) 1.04 (0.46-2.36) 33 (20-46) 1.56 (0.64-3.96) Lung-involved 15 4 15 (3-34) 1.28 (0.53-3.01) 57 (27-79) 0.97 (0.31-3.19) 14 (2-40) 0.37 (0.05-1.47) Liver-involved 15 3 15 (3-35) 1.45 (0.63-3.32) 67 (38-88) 1.57 (0.51-5.40) 13 (2-40) 0.33 (0.05-1.32)