scholarly journals PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis

2020 ◽  
Author(s):  
Robert Seifert ◽  
Katharina Kessel ◽  
Katrin Schlack ◽  
Manuel Weber ◽  
Ken Herrmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Tumor Volume ◽  
Cox Regression ◽  
Radioligand Therapy ◽  
Total Tumor Volume ◽  
Psma Pet ◽  
Pet Ct ◽  
Lesion Number ◽  
Patients At Risk

Abstract Introduction [177Lu]Lu-PSMA-617 (Lu-PSMA) radioligand therapy is an emerging treatment option for patients with end-stage prostate cancer. However, response to Lu-PSMA therapy is only achieved in approximately half of patients. It is clinically important to identify patients at risk of poor outcome. Therefore, the aim of this study was to evaluate pretherapeutic PSMA PET derived total tumor volume and related metrics as prognosticators of overall survival in patients receiving Lu-PSMA therapy. Methods A total number of 110 patients form the Departments of Nuclear Medicine Münster and Essen were included in this retrospective analysis. Baseline PSMA PET-CT was available for all patients. Employing a previously published approach, all tumor lesions were semi-automatically delineated in PSMA PET-CT acquisitions. Total lesion number, total tumor volume (PSMA-TV), total lesion uptake (PSMA-TLU = PSMA-TV * SUVmean), and total lesion quotient (PSMA-TLQ = PSMA-TV / SUVmean) were quantified for each patient. Log2 transformation was used for regressions. Results Lesion number, PSMA-TV, and PSMA-TLQ were prognosticators of overall survival (HR = 1.255, p = 0.009; HR = 1.299, p = 0.005; HR = 1.326, p = 0.002). In a stepwise backward Cox regression including lesion number, PSMA-TV, PSA, LDH, and PSMA-TLQ, only the latter two remained independent and statistically significant negative prognosticators of overall survival (HR = 1.632, p = 0.011; HR = 1.239, p = 0.024). PSMA-TLQ and LDH were significant negative prognosticators in multivariate Cox regression in contrast to PSA value. Conclusion PSMA-TV was a statistically significant negative prognosticator of overall survival in patients receiving Lu-PSMA therapy. PSMA-TLQ was an independent and superior prognosticator of overall survival compared with PSMA-TV.

scholarly journals Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [177Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4270
Author(s):  
Philipp E. Hartrampf ◽  
Constantin Lapa ◽  
Sebastian E. Serfling ◽  
Andreas K. Buck ◽  
Anna Katharina Seitz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radioligand Therapy ◽  
Psma Pet ◽  
Number Of Patients ◽  
Pet Ct ◽  
Significant Difference ◽  
Tracer Imaging ◽  
Prognostic Implications ◽  
Dual Tracer

Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [18F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA−) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA− lesions during or after PSMA RLT. Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA− lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA− lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA− lesion were compared to patients without any FDG+/PSMA− lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups. Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA− metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA− lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA− findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA− lesions (p = 0.442). Conclusion: This study shows that FDG+/PSMA− lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions.

Relevant tumor sink effect in prostate cancer patients receiving 177Lu-PSMA-617 radioligand therapy

2018 ◽  
Vol 57 (01) ◽  
pp. 19-25 ◽  
Author(s):  
Christian Filss ◽  
Alexander Heinzel ◽  
Berthold Miiller ◽  
Andreas Vogg ◽  
Karl-Josef Langen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Tumor Volume ◽  
Standardized Uptake Value ◽  
Whole Body ◽  
Total Tumor Volume ◽  
Pet Ct ◽  
Sink Effect ◽  
Tumor Load ◽  
Pet Ct Scan

SummaryAim: In metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in 177Lu-PSMA-617 therapy was evaluated.Methods: Eleven consecutive prostate cancer patients receiving a first cylcle of 177Lu-PSMA-617 (administered activity of approximately 6GBq) were included. The 68Ga-PSMA-11 PET/CT scan previous to therapy was used to determine TTV and SG uptake (glandulae submandibularis) employing PMOD version 3.403 with different 68Ga-PSMA-11 thresholds based on the standardized uptake value (SUV).The kidney dose was estimated with the software ULMDOS using planar whole-body scintigrams.Results: Kidney dose and SG uptake was inversely correlated to TTV, indicating high kidney dose and high SG uptake in case of low tumor load and low kidney dose and low SG uptake in case of high tumor load.Conclusion: Our data support the hypothesis that in 177Lu-PSMA-617 therapy an individualized treatment activity based on total tumor volume could be beneficiary.

Prognostic markers for overall survival and outcome to LuPSMA radionuclide treatment in patients with metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5548-5548
Author(s):  
Andrei Gafita ◽  
Jeremie Calais ◽  
Hui Wang ◽  
Manuel Weber ◽  
Hendrik Rathke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Retrospective Analysis ◽  
Survival Data ◽  
Prognostic Markers ◽  
Castration Resistant Prostate Cancer ◽  
Factors Associated ◽  
Psma Pet ◽  
Pet Ct ◽  
Time Since Diagnosis

5548 Background: The aim of this international multicenter retrospective analysis was to identify prognostic markers for the clinical outcome in late-stage mCRPC patients treated with 177Lutetium-prostate-specific membrane antigen (LuPSMA) radionuclide treatment. Methods: Patients with progressive mCRPC treated with LuPSMA at six centers in Germany, USA, and Australia were considered for inclusion. Eligible patients had 24 predefined, pretherapeutic covariates (demographics, prior mCRPC treatments, and PSMA PET/CT derived parameters) and survival data available. Endpoints included overall survival (OS) and PSA progression-free survival (PSA-PFS). Covariates were tested using univariate and mulitvariate proportional hazards regression Cox models. Results: 267/414 (64%) patients met inclusion criteria and were analyzed. 113 patients participated in clinical trials (ACTRN12615000912583, NCT03042312), while 154 were enrolled in compassionate-access programs. After a median follow-up of 22.5 months, median OS was 13.0 months (95%CI 11.6-14.4); 83% of the patients died. Median PSA-PFS was 4.0 months (95%CI 3.2-4.7). In the multivariate analysis, factors associated with shorter OS were: shorter time since diagnosis of prostate cancer (HR=2.04; p=0.002), lower number of prior systemic therapies (≤3; HR=1.56; p=0.006), prior exposure to chemotherapy (HR=1.42; p=0.05), lower hemoglobin levels (HR=1.13; p=0.002), higher number of lesions (≥20: HR=1.53; p=0.009), multiple sites of metastases (bone/LN only vs. bone + LN; HR=1.39; p=0.03) and visceral involvement (M1c) (HR=1.45; p=0.01). Factors associated with longer PSA-PFS were: longer time since diagnosis of prostate cancer (HR=0.44; p<0.001), higher hemoglobin levels (HR=0.32; p=0.03), presence of pelvic lymph nodes (LN) metastasis (N1) (HR=0.68; p=0.01), no distant lymph node metastases (M1a) (HR=0.66; p=0.01), no skeleton involvement (HR=0.44; p=0.01), no visceral metastases (M1c) (HR=0.51; p<0.001), higher PSMA-positive tumor volume (HR=0.87; p=0.04), and higher SUVmean (HR=0.94; p=0.002). Conclusions: This retrospective analysis identified prognostic factors for survival and treatment response to LuPSMA. Along with the conventional risk factors in mCRPC, PSMA PET/CT can be a useful tool for stratifying patients and guide patient’s selection for LuPSMA radionuclide treatment.

scholarly journals PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

2021 ◽  
Author(s):  
M. J. M. Uijen ◽  
Y. H. W. Derks ◽  
R. I. J. Merkx ◽  
M. G. M. Schilham ◽  
J. Roosen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Current Knowledge ◽  
Salivary Gland Cancer ◽  
Clinical Implementation ◽  
Radioligand Therapy ◽  
Psma Pet ◽  
Pet Ct ◽  
Specific Membrane ◽  
Psma Expression

AbstractIn the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [177Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.

Theranostics of Metastatic Prostate Cancer Applying 64Cu/18F/68Ga PSMA PET-CT and 177Lu Radiopharmaceuticals

2020 ◽  
Vol 13 ◽  
Author(s):  
Siroos Mirzaei ◽  
Fairoz Mohammed ◽  
Shahin Zandieh
Keyword(s):  
Prostate Cancer ◽  
Nuclear Medicine ◽  
Radionuclide Therapy ◽  
Metastatic Prostate Cancer ◽  
Therapy Response ◽  
Radioligand Therapy ◽  
Psma Pet ◽  
Pet Ct ◽  
Diagnostic Sensitivity And Specificity ◽  
Tumor Types

: The successful use of theranostic twins in neuroendocrine tumors (NET) was the pioneering approach to radionuclide therapy in other tumor types. 64Cu/18F PSMA for molecular imaging with PET-CT and peptide radioligand therapy (PRLT) with 177Lu labeled PSMA inhibitors are the next theranostic twins in nuclear medicine. 68Ga/ 64Cu/18F PSMA PET-CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity and can be used to select patients for PRLT and evaluate therapy response. Radionuclide therapy with 177Lu-PSMA inhibitors has been shown to be effective in the treatment of metastatic CRPC.

Treatment outcome and identification of factors influencing overall survival after Lu-177-PSMA-617 radioligand therapy in metastatic prostate cancer

2021 ◽  
Author(s):  
Charlotte A. Schneider ◽  
Philipp Täger ◽  
Jochen Hammes ◽  
Thomas Fischer ◽  
Alexander Drzezga ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Regression Analysis ◽  
Cox Regression ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Cox Regression Analysis ◽  
Cumulative Activity

Abstract Objective To examine the clinical benefit of Lu-177-PSMA-617 radioligand therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Between November 2014 and December 2018, a total of 56 consecutive patients (median age 69.5 years; range 55–84 years) with mCRPC were included in this retrospective analysis. Patients received between 1 and 4 therapy cycles with a mean activity of 6.8 GBq per cycle. Biochemical response was evaluated using Prostate Cancer Working Group Criteria 3 (PCWG 3). Survival was assessed using Kaplan-Meier estimates and Cox proportional hazards regression analysis. This retrospective study was approved by the local ethics committee. Results A total of 139 treatment cycles with Lu-177-PSMA-617 were performed. A decline of 50% or more of prostate-specific antigen (PSA) level occurred in 54% and a PSA decline of any amount in 65% of patients. The estimated median overall survival (OS) was 16 months, in the chemotherapy subgroup 14 months. A longer OS was associated with a PSA-decline ≥50%, more than 2 cycles of therapy, cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l]. These identified predictors remained significant on uni- and multivariate Cox regression analysis. Moreover, 40% of the patients who were non-responders after the first therapy cycle turned into responders after the second one. Conclusion PSA-decline ≥50%, a cumulative activity >15 GBq and an initial alkaline phosphatase ≤ 220 [U/l] were identified as key predictors of prolonged OS in patients with mCRPC. In contrast rapid clinical deterioration mostly due to skeletal carcinomatosis resulted in early treatment failure.

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