scholarly journals Early molecular imaging response assessment based on determination of total viable tumor burden in [68Ga]Ga-PSMA-11 PET/CT independently predicts overall survival in [177Lu]Lu-PSMA-617 radioligand therapy

2021 ◽  
Author(s):  
Florian Rosar ◽  
Felix Wenner ◽  
Fadi Khreish ◽  
Sebastian Dewes ◽  
Gudrun Wagenpfeil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Molecular Imaging ◽  
Multivariable Analysis ◽  
Response Assessment ◽  
Tumor Burden ◽  
Whole Body ◽  
Biochemical Response ◽  
Radioligand Therapy ◽  
Pet Ct ◽  
Imaging Response

Abstract Purpose In patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT), the predictive value of PSMA PET/CT-derived response is still under investigation. Early molecular imaging response based on total viable tumor burden and its association with overall survival (OS) was explored in this study. Methods Sixty-six mCRPC patients who received [177Lu]Lu-PSMA-617 RLT within a prospective patient registry (REALITY Study, NCT04833517) were analyzed. Patients received a [68Ga]Ga-PSMA-11 PET/CT scan before the first and after the second cycle of PSMA-RLT. Total lesion PSMA (TLP) was determined by semiautomatic whole-body tumor segmentation. Molecular imaging response was assessed by change in TLP and modified PERCIST criteria. Biochemical response was assessed using standard serum PSA and PCWG3 criteria. Both response assessment methods and additional baseline parameters were analyzed regarding their association with OS by univariate and multivariable analysis. Results By molecular imaging, 40/66 (60.6%) patients showed partial remission (PR), 19/66 (28.7%) stable disease (SD), and 7/66 (10.6%) progressive disease (PD). Biochemical response assessment revealed PR in 34/66 (51.5%) patients, SD in 20/66 (30.3%), and PD in 12/66 (18.2%). Response assessments were concordant in 49/66 (74.3%) cases. On univariate analysis, both molecular and biochemical response (p = 0.001 and 0.008, respectively) as well as two baseline characteristics (ALP and ECOG) were each significantly associated with OS. The median OS of patients showing molecular PR was 24.6 versus 10.7 months in the remaining patients (with SD or PD). On multivariable analysis molecular imaging response remained an independent predictor of OS (p = 0.002), eliminating biochemical response as insignificant (p = 0.515). Conclusion The new whole-body molecular imaging–derived biomarker, early change of total lesion PSMA (TLP), independently predicts overall survival in [177Lu]Lu-PSMA-617 RLT in mCRPC, outperforming conventional PSA-based response assessment. TLP might be considered a more distinguished and advanced biomarker for monitoring PSMA-RLT over commonly used serum PSA.

scholarly journals Response Assessment and Prediction of Progression-Free Survival by 68Ga-PSMA-11 PET/CT Based on Tumor-to-Liver Ratio (TLR) in Patients with mCRPC Undergoing 177Lu-PSMA-617 Radioligand Therapy

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1099
Author(s):  
Fadi Khreish ◽  
Mona Wiessner ◽  
Florian Rosar ◽  
Zaidoon Ghazal ◽  
Amir Sabet ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Performance Status ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Pet Ct

At present, little is known about the molecular imaging-based response assessment of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with 177Lutetium (177Lu-PSMA-617 RLT) in metastatic castration-resistant prostate cancer (mCRPC). Our study evaluated the response to RLT using both molecular imaging and biochemical response assessments, and their potential prediction of progression-free survival (PFS). Fifty-one consecutive patients given two cycles of RLT at 6-week intervals were analyzed retrospectively. 68Ga-PSMA-11 PET/CT was obtained about 2 weeks prior to the first and 4–6 weeks after the second cycle. Molecular imaging-based response using SUVpeak and tumor-to-liver ratio (TLR) was determined by modified PERCIST criteria. ∆TLR and ∆SUV were significantly correlated with ∆PSA (p < 0.001, each). After a median follow-up of 49 months, the median PFS (95% CI) was 8.0 (5.9–10.1) months. In univariate analysis, responders showing partial remission (PRPSA and PRTLR) had significantly (p < 0.001, each) longer PFS (median: 10.5 and 9.3 months) than non-responders showing either stable or progressive disease (median: 4.0 and 3.5 months). Response assessment using SUVpeak failed to predict survival. In multivariable analysis, response assessment using TLR was independently associated with PFS (p < 0.001), as was good performance status (p = 0.002). Molecular imaging-based response assessment with 68Ga-PSMA-11 PET/CT using normalization of the total lesion PSMA over healthy liver tissue uptake (TLR) could be an appropriate biomarker to monitor RLT in mCRPC patients and to predict progression-free survival (PFS) of this treatment modality.

scholarly journals Efficacy and Safety of [225Ac]Ac-PSMA-617 Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Highly Advanced mCRPC with Poor Prognosis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 722
Author(s):  
Florian Rosar ◽  
Jonas Krause ◽  
Mark Bartholomä ◽  
Stephan Maus ◽  
Tobias Stemler ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Efficacy And Safety ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Pet Ct ◽  
Visceral Metastases ◽  
Grade 3

The use of 225Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with 177Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in 177Lu-naive mCRPC patients (n = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [68Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one [225Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort.

scholarly journals Prognostic implications of dual tracer PET/CT: PSMA ligand and [18F]FDG PET/CT in patients undergoing [177Lu]PSMA radioligand therapy

2020 ◽  
Author(s):  
Kerstin Michalski ◽  
Juri Ruf ◽  
Christian Goetz ◽  
Anna Katharina Seitz ◽  
Andreas K. Buck ◽  
...  
Keyword(s):  
Overall Survival ◽  
Fdg Pet ◽  
Tumor Burden ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Rank Analysis ◽  
Fdg Uptake ◽  
Psma Ligand ◽  
Pet Ct ◽  
Fdg Pet Ct

Abstract Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with 177Lu-labeled PSMA ligands has achieved remarkable results in advanced disease stages of metastatic castration-resistant prostate cancer (mCRPC). However, not all patients benefit from this therapy. Different treatment responses could be explained by tumor heterogeneity triggered by progression and the number of prior treatments. PSMA-negative lesions can be missed on PSMA ligand PET/CT, which subsequently results in an underestimation of tumor burden. Conversely, high FDG uptake may also be an indicator of tumor aggressiveness and thus a poor prognostic marker for response to RLT and overall survival (OS). The aim of this analysis was to investigate the prognostic value of combined PSMA ligand PET/CT and [18F]fluorodeoxyglucose (FDG) PET/CT for outcome prediction in patients undergoing RLT. Materials and methods This bicentric analysis included 54 patients with mCRPC who underwent both FDG and PSMA ligand PET/CT imaging before RLT. In all patients, the pattern of PSMA ligand and FDG uptake was visually assessed. Patients with at least one FDG-positive, but PSMA-negative (FDG+/PSMA−) lesions were compared to patients without any FDG+/PSMA− lesions. A log-rank analysis was used to assess the difference in OS between subgroups. Results Median OS was 11 ± 1.8 months (95% CI 7.4–14.6). A significantly lower OS (p < 0.001) was found in patients with at least one FDG+/PSMA− lesion at baseline PET/CTs (n = 18) with a median OS of 6.0 ± 0.5 months (95% CI: 5.0–7.0 months). In comparison, patients without any FDG+/PSMA− lesions (n = 36) had a median OS of 16.0 ± 2.5 months (95% CI: 11.2–20.8 months). Conclusion FDG+/PSMA− lesions are a negative predictor of overall survival in patients with mCRPC undergoing RLT. However, it remains to be determined if patients with FDG+/PSMA− lesions should be excluded from PSMA RLT.

scholarly journals Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 149
Author(s):  
Felix Kind ◽  
Thomas F. Fassbender ◽  
Geoffroy Andrieux ◽  
Melanie Boerries ◽  
Philipp T. Meyer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Therapeutic Option ◽  
Short Interval ◽  
Early Time ◽  
Biochemical Response ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Biochemical Progression ◽  
Imaging Response

Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS.

Determination of whole-body tumour burden on [68Ga]PSMA-11 PET/CT for response assessment of [177Lu]PSMA-617 radioligand therapy: a retrospective analysis of serum PSA level and imaging derived parameters before and after two cycles of therapy

2019 ◽  
Vol 58 (06) ◽  
pp. 443-450
Author(s):  
Kerstin Michalski ◽  
Michael Mix ◽  
Philipp T. Meyer ◽  
Juri Ruf
Keyword(s):  
Standardized Uptake Value ◽  
Response Assessment ◽  
Tracer Uptake ◽  
Whole Body ◽  
Castration Resistant Prostate Cancer ◽  
Tumour Burden ◽  
Radioligand Therapy ◽  
Psma Pet ◽  
Pet Ct ◽  
Before And After

Abstract Aim In patients with metastasized castration-resistant prostate cancer a reliable imaging-based therapy response assessment in addition to PSA kinetics is desirable. Recently, measurements of whole-body tumour burden by [68Ga]PSMA-11 PET/CT have been reported for response assessment in oligometastasic patients. The present study investigated the association of PSMA PET derived parameters and serum PSA level before and after [177Lu]PSMA-617 radioligand therapy (RLT). Methods This retrospective study assessed whole-body PSMA tumour volume (PSMA-TV) in 10 patients with multifocal to diffuse metastases before and after 2 cycles of RLT using volume of interest (VOI) analysis. A standardized uptake value (SUV) threshold-based approach was used to semi-automatically delineate all voxels with a SUV ≥ 2.0 g/ml using the software ROVER® (ABX Radeberg, Germany). Voxels with physiological tracer uptake (e. g. kidneys) were excluded manually. Correlations between PSMA-TV and serum PSA level before and after two cycles of RLT as well as changes thereof (ΔPSMA-TV and ΔPSA, respectively) were calculated. Results Changes of ΔPSMA-TV and ΔPSA were concordant in 7 of 10 patients. Whereas a good correlation was found between PSMA-TV and PSA before RLT (ρ = 0.81, p = 0.0049), this correlation was attenuated after RLT (ρ = 0.64, p = 0.0479). Consequently, no association was found between ΔPSMA-TV and ΔPSA (ρ = 0.39, p = 0.26). Conclusion The attenuation of the correlation of PSA and PSMA-TV after RLT suggests that in patients with advanced disease the comparison of imaging based parameters such as PSMA-TV and PSA level might be useful for an adequate monitoring of treatment response.

scholarly journals Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after 177Lu-PSMA-617 Radioligand Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 428
Author(s):  
Friederike Völter ◽  
Lena Mittlmeier ◽  
Astrid Gosewisch ◽  
Julia Brosch-Lenz ◽  
Franz Josef Gildehaus ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Single Photon ◽  
Photon Emission ◽  
Whole Body ◽  
Biochemical Response ◽  
Emission Computed Tomography ◽  
Radioligand Therapy ◽  
Index Lesion ◽  
Recist 1.1 ◽  
Psma Pet

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative 177Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine.

scholarly journals PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2938
Author(s):  
Liam Widjaja ◽  
Rudolf A. Werner ◽  
Tobias L. Ross ◽  
Frank M. Bengel ◽  
Thorsten Derlin
Keyword(s):  
Prostate Cancer ◽  
Whole Body ◽  
Biochemical Response ◽  
Clinical Parameters ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Psa Response ◽  
High Age ◽  
Psma Expression

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.

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