BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) has demonstrated efficacy and tolerability with a dose-response effect in phase I/II trials in men with metastatic castration-resistant prostate cancer (mCRPC). The need for positive PSMA imaging before PSMA-TRT to select patients is largely practiced, but its utility is not proven. Given target heterogeneity, developing a biomarker to identify the optimal patient population remains an unmet need. The aim of this study was to assess PSMA uptake by imaging and response to PSMA-TRT. METHODS: We performed an analysis of men with mCRPC enrolled in sequential prospective phase I/II trials of PSMA-TRT. Each patient had baseline PSMA imaging by planar 111 In and/or 177 Lu SPECT (N = 171) or 68 Ga-PSMA-11 PET/CT (N = 44), but the results were not used to include/exclude treatment. Semiquantitative imaging scores (IS) on a 0-4 scale were assigned based on PSMA uptake in tumors compared to liver uptake. We compared the ≥50% PSA decline response proportions between low (0-1) and high (2-4) PSMA IS using the χ2 -test. We used multivariable logistic regression analysis to understand the relationship between independent and dependent variables, including IS, radionuclide activity (dose) administered, CALGB (Halabi) prognostic risk score, prior taxane use. RESULTS: 215 men with progressive mCRPC received PSMA-TRT as follows: 177 Lu-J591 (n = 137), 177 Lu-PSMA-617 (n = 44), 90 Y-J591 (n = 28), 177 Lu-J591 + 177 Lu-PSMA-617 (n = 6). High PSMA expression (IS 2-4) was found in 160 (74.4%) patients and was significantly associated with more frequent ≥ 50% PSA reduction (26.2 vs. 7.3%, p = .006). On multivariate logistic regression analysis, higher IS was associated with a ≥50% decrease in PSA, even after accounting for CALGB (Halabi) prognostic score, the dose administered, and previous taxane use (OR, 4.72; 95% CI, 1.71-16.85; p = .006). Patients with low PSMA expression (N = 55, 24.7%) were less likely to respond. Thirteen of 26 (50%) with no PSMA uptake (IS = 0) had post-PSMA-TRT PSA decline with 2 (7.7%) having ≥ 50% PSA declines. CONCLUSION: Collectively, the data provide evidence in favor of the hypothesis that patients with high PSMA uptake and high administered radionuclide dose correlate with a higher chance of response.
BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) has demonstrated efficacy and tolerability with a dose-response effect in phase I/II trials in men with metastatic castration-resistant prostate cancer (mCRPC). The need for positive PSMA imaging before PSMA-TRT to select patients is largely practiced, but its utility is not proven. Given target heterogeneity, developing a biomarker to identify the optimal patient population remains an unmet need. The aim of this study was to assess PSMA uptake by imaging and response to PSMA-TRT. METHODS: We performed an analysis of men with mCRPC enrolled in sequential prospective phase I/II trials of PSMA-TRT. Each patient had baseline PSMA imaging by planar 111 In and/or 177 Lu SPECT (N = 171) or 68 Ga-PSMA-11 PET/CT (N = 44), but the results were not used to include/exclude treatment. Semiquantitative imaging scores (IS) on a 0-4 scale were assigned based on PSMA uptake in tumors compared to liver uptake. We compared the ≥50% PSA decline response proportions between low (0-1) and high (2-4) PSMA IS using the χ2 -test. We used multivariable logistic regression analysis to understand the relationship between independent and dependent variables, including IS, radionuclide activity (dose) administered, CALGB (Halabi) prognostic risk score, prior taxane use. RESULTS: 215 men with progressive mCRPC received PSMA-TRT as follows: 177 Lu-J591 (n = 137), 177 Lu-PSMA-617 (n = 44), 90 Y-J591 (n = 28), 177 Lu-J591 + 177 Lu-PSMA-617 (n = 6). High PSMA expression (IS 2-4) was found in 160 (74.4%) patients and was significantly associated with more frequent ≥ 50% PSA reduction (26.2 vs. 7.3%, p = .006). On multivariate logistic regression analysis, higher IS was associated with a ≥50% decrease in PSA, even after accounting for CALGB (Halabi) prognostic score, the dose administered, and previous taxane use (OR, 4.72; 95% CI, 1.71-16.85; p = .006). Patients with low PSMA expression (N = 55, 24.7%) were less likely to respond. Thirteen of 26 (50%) with no PSMA uptake (IS = 0) had post-PSMA-TRT PSA decline with 2 (7.7%) having ≥ 50% PSA declines. CONCLUSION: Collectively, the data provide evidence in favor of the hypothesis that patients with high PSMA uptake and high administered radionuclide dose correlate with a higher chance of response.
Authors: Michael S Hofman; Louise Emmett; John Violet; Alison Y Zhang; Nicola J Lawrence; Martin Stockler; Roslyn J Francis; Amir Iravani; Scott Williams; Arun Azad; Andrew Martin; Margaret McJannett; Ian D Davis Journal: BJU Int Date: 2019-10-22 Impact factor: 5.588
Authors: Alexander Heinzel; Dima Boghos; Felix M Mottaghy; Florian Gaertner; Markus Essler; Dirk von Mallek; Hojjat Ahmadzadehfar Journal: Eur J Nucl Med Mol Imaging Date: 2019-01-29 Impact factor: 9.236
Authors: Sue Ping Thang; John Violet; Shahneen Sandhu; Amir Iravani; Tim Akhurst; Grace Kong; Aravind Ravi Kumar; Declan G Murphy; Scott G Williams; Rodney J Hicks; Michael S Hofman Journal: Eur Urol Oncol Date: 2018-12-13
Authors: Justin Ferdinandus; John Violet; Shahneen Sandhu; Rodney J Hicks; Aravind S Ravi Kumar; Amir Iravani; Grace Kong; Tim Akhurst; Sue Ping Thang; Declan G Murphy; Scott Williams; Michael S Hofman Journal: Eur J Nucl Med Mol Imaging Date: 2020-03-05 Impact factor: 9.236
Authors: John Violet; Price Jackson; Justin Ferdinandus; Shahneen Sandhu; Tim Akhurst; Amir Iravani; Grace Kong; Aravind Ravi Kumar; Sue Ping Thang; Peter Eu; Mark Scalzo; Declan Murphy; Scott Williams; Rodney J Hicks; Michael S Hofman Journal: J Nucl Med Date: 2018-10-05 Impact factor: 10.057
Authors: John Violet; Shahneen Sandhu; Amir Iravani; Justin Ferdinandus; Sue-Ping Thang; Grace Kong; Aravind Ravi Kumar; Tim Akhurst; David A Pattison; Alexis Beaulieu; Jennifer Mooi; Ben Tran; Christina Guo; Victor Kalff; Declan G Murphy; Price Jackson; Peter Eu; Mark Scalzo; Scott Williams; Rodney J Hicks; Michael S Hofman Journal: J Nucl Med Date: 2019-11-15 Impact factor: 11.082
Authors: Alec Paschalis; Beshara Sheehan; Ruth Riisnaes; Daniel Nava Rodrigues; Bora Gurel; Claudia Bertan; Ana Ferreira; Maryou B K Lambros; George Seed; Wei Yuan; David Dolling; Jon C Welti; Antje Neeb; Semini Sumanasuriya; Pasquale Rescigno; Diletta Bianchini; Nina Tunariu; Suzanne Carreira; Adam Sharp; Wim Oyen; Johann S de Bono Journal: Eur Urol Date: 2019-07-22 Impact factor: 20.096