Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer

Bernhard Grubmüller; Daniela Senn; Gero Kramer; Pascal Baltzer; David D'Andrea; Karl Hermann Grubmüller; Markus Mitterhauser; Harald Eidherr; Alexander R Haug; Wolfgang Wadsak; Sarah Pfaff; Shahrokh F Shariat; Marcus Hacker; Markus Hartenbach

doi:10.1007/s00259-018-4236-4

Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer

Bernhard Grubmüller, Daniela Senn, Gero Kramer, Pascal Baltzer, David D'Andrea, Karl Hermann Grubmüller, Markus Mitterhauser, Harald Eidherr, Alexander R Haug, Wolfgang Wadsak, Sarah Pfaff, Shahrokh F Shariat, Marcus Hacker, Markus Hartenbach

Division of Urology (University Hospital Krems)

Research output: Journal article (peer-reviewed) › Journal article

114 Citations (Scopus)

Abstract

PURPOSE: The first aim of this study was to evaluate 68Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS).

METHODS: We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis.

RESULTS: The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1-1.003, p = 0.04, and HR 1.004, 95% CI 1.001-1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009-1.14, p = 0.02).

CONCLUSION: TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.

Original language	English
Pages (from-to)	1063-1072
Number of pages	10
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	46
Issue number	5
DOIs	https://doi.org/10.1007/s00259-018-4236-4
Publication status	Published - 01 May 2019

Keywords

Aged
Dipeptides/therapeutic use
Follow-Up Studies
Gallium Isotopes
Gallium Radioisotopes
Heterocyclic Compounds, 1-Ring/therapeutic use
Humans
Ligands
Lutetium
Male
Membrane Glycoproteins
Neoplasm Metastasis
Organometallic Compounds
Positron Emission Tomography Computed Tomography
Prostate-Specific Antigen/metabolism
Prostatic Neoplasms, Castration-Resistant/diagnostic imaging
ROC Curve
Retrospective Studies
Survival Analysis
Treatment Outcome
Hybrid imaging
Metastatic prostate cancer
PET/MRI
PSMA ligand
PET/CT

ASJC Scopus subject areas

Radiology, Nuclear Medicine and Imaging

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10.1007/s00259-018-4236-4

Cite this

Grubmüller, B., Senn, D., Kramer, G., Baltzer, P., D'Andrea, D., Grubmüller, K. H., Mitterhauser, M., Eidherr, H., Haug, A. R., Wadsak, W., Pfaff, S., Shariat, S. F., Hacker, M., & Hartenbach, M. (2019). Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer. European Journal of Nuclear Medicine and Molecular Imaging, 46(5), 1063-1072. https://doi.org/10.1007/s00259-018-4236-4

@article{37a3472e6bdd4b3e8be3c03cc04c4ae3,

title = "Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer",

abstract = "PURPOSE: The first aim of this study was to evaluate 68Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS).METHODS: We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis.RESULTS: The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1-1.003, p = 0.04, and HR 1.004, 95% CI 1.001-1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009-1.14, p = 0.02).CONCLUSION: TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.",

keywords = "Aged, Dipeptides/therapeutic use, Follow-Up Studies, Gallium Isotopes, Gallium Radioisotopes, Heterocyclic Compounds, 1-Ring/therapeutic use, Humans, Ligands, Lutetium, Male, Membrane Glycoproteins, Neoplasm Metastasis, Organometallic Compounds, Positron Emission Tomography Computed Tomography, Prostate-Specific Antigen/metabolism, Prostatic Neoplasms, Castration-Resistant/diagnostic imaging, ROC Curve, Retrospective Studies, Survival Analysis, Treatment Outcome, Hybrid imaging, Metastatic prostate cancer, PET/MRI, PSMA ligand, PET/CT",

author = "Bernhard Grubm{\"u}ller and Daniela Senn and Gero Kramer and Pascal Baltzer and David D'Andrea and Grubm{\"u}ller, {Karl Hermann} and Markus Mitterhauser and Harald Eidherr and Haug, {Alexander R} and Wolfgang Wadsak and Sarah Pfaff and Shariat, {Shahrokh F} and Marcus Hacker and Markus Hartenbach",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2019",

month = may,

day = "1",

doi = "10.1007/s00259-018-4236-4",

language = "English",

volume = "46",

pages = "1063--1072",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer Verlag",

number = "5",

}

Grubmüller, B, Senn, D, Kramer, G, Baltzer, P, D'Andrea, D, Grubmüller, KH, Mitterhauser, M, Eidherr, H, Haug, AR, Wadsak, W, Pfaff, S, Shariat, SF, Hacker, M & Hartenbach, M 2019, 'Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer', European Journal of Nuclear Medicine and Molecular Imaging, vol. 46, no. 5, pp. 1063-1072. https://doi.org/10.1007/s00259-018-4236-4

Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer. / Grubmüller, Bernhard; Senn, Daniela; Kramer, Gero et al.
In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 46, No. 5, 01.05.2019, p. 1063-1072.

Research output: Journal article (peer-reviewed) › Journal article

TY - JOUR

T1 - Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer

AU - Grubmüller, Bernhard

AU - Senn, Daniela

AU - Kramer, Gero

AU - Baltzer, Pascal

AU - D'Andrea, David

AU - Grubmüller, Karl Hermann

AU - Mitterhauser, Markus

AU - Eidherr, Harald

AU - Haug, Alexander R

AU - Wadsak, Wolfgang

AU - Pfaff, Sarah

AU - Shariat, Shahrokh F

AU - Hacker, Marcus

AU - Hartenbach, Markus

PY - 2019/5/1

Y1 - 2019/5/1

N2 - PURPOSE: The first aim of this study was to evaluate 68Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS).METHODS: We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis.RESULTS: The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1-1.003, p = 0.04, and HR 1.004, 95% CI 1.001-1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009-1.14, p = 0.02).CONCLUSION: TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.

AB - PURPOSE: The first aim of this study was to evaluate 68Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS).METHODS: We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis.RESULTS: The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1-1.003, p = 0.04, and HR 1.004, 95% CI 1.001-1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009-1.14, p = 0.02).CONCLUSION: TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.

KW - Aged

KW - Dipeptides/therapeutic use

KW - Follow-Up Studies

KW - Gallium Isotopes

KW - Gallium Radioisotopes

KW - Heterocyclic Compounds, 1-Ring/therapeutic use

KW - Humans

KW - Ligands

KW - Lutetium

KW - Male

KW - Membrane Glycoproteins

KW - Neoplasm Metastasis

KW - Organometallic Compounds

KW - Positron Emission Tomography Computed Tomography

KW - Prostate-Specific Antigen/metabolism

KW - Prostatic Neoplasms, Castration-Resistant/diagnostic imaging

KW - ROC Curve

KW - Retrospective Studies

KW - Survival Analysis

KW - Treatment Outcome

KW - Hybrid imaging

KW - Metastatic prostate cancer

KW - PET/MRI

KW - PSMA ligand

KW - PET/CT

UR - http://www.scopus.com/inward/record.url?scp=85058839078&partnerID=8YFLogxK

U2 - 10.1007/s00259-018-4236-4

DO - 10.1007/s00259-018-4236-4

M3 - Journal article

C2 - 30569186

SN - 1619-7070

VL - 46

SP - 1063

EP - 1072

JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 5

ER -

Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer

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