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.

scholarly journals Detection rates of recurrent prostate cancer: 68Gallium (Ga)-labelled prostate-specific membrane antigen versus choline PET/CT scans. A systematic review

2019 ◽  
Vol 11 ◽  
pp. 175628721881579 ◽  
Author(s):  
Masood Moghul ◽  
Bhaskar Somani ◽  
Tim Lane ◽  
Nikhil Vasdev ◽  
Brian Chaplin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Ct Scans ◽  
Prostate Specific Membrane Antigen ◽  
Recurrent Prostate Cancer ◽  
Detection Rates ◽  
Psma Pet ◽  
Pet Ct ◽  
Significant Difference ◽  
Specific Membrane

Background: The aim of this work was to assess the use of prostate-specific membrane antigen (PSMA)-labelled radiotracers in detecting the recurrence of prostate cancer. PSMA is thought to have higher detection rates when utilized in positron emission tomography (PET)/computed tomography (CT) scans, particularly at lower prostate-specific antigen (PSA) levels, compared with choline-based scans. Methods: A systematic review was conducted comparing choline and PSMA PET/CT scans in patients with recurrent prostate cancer following an initial curative attempt. The primary outcomes were overall detection rates, detection rates at low PSA thresholds, difference in detection rates and exclusive detection rates on a per-person analysis. Secondary outcome measures were total number of lesions, exclusive detection by each scan on a per-lesion basis and adverse side effects. Results: Overall detection rates were 79.8% for PSMA and 66.7% for choline. There was a statistically significant difference in detection rates favouring PSMA [OR (M–H, random, 95% confidence interval (CI)) 2.27 (1.06, 4.85), p = 0.04]. Direct comparison was limited to PSA < 2 ng/ml in two studies, with no statistically significant difference in detection rates between the scans [OR (M–H, random, 95% CI) 2.37 (0.61, 9.17) p = 0.21]. The difference in detection on the per-patient analysis was significantly higher in the PSMA scans ( p < 0.00001). All three studies reported higher lymph node, bone metastasis and locoregional recurrence rates in PSMA. Conclusions: PSMA PET/CT has a better performance compared with choline PET/CT in detecting recurrent disease both on per-patient and per-lesion analysis and should be the imaging modality of choice while deciding on salvage and nonsystematic metastasis-directed therapy strategies.

The “ProPSMA Study” clinical trial protocol: A prospective randomized multi-center study of the impact of Ga-68 PSMA PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS138-TPS138 ◽  
Author(s):  
Michael Hofman ◽  
Declan G. Murphy ◽  
Scott Williams ◽  
Tatenda Nzenza ◽  
Alan Herschtal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Conventional Imaging ◽  
Curative Intent ◽  
High Risk Prostate Cancer ◽  
Psma Pet ◽  
Pet Ct ◽  
Risk Prostate Cancer

TPS138 Background: Disease persistence or relapse following curative-intent surgery or radiotherapy of high-risk prostate cancer is not uncommon. This is attributable, in part, to a failure of accurate staging with diagnostic imaging being insensitive for detection of small volume metastatic disease. Prostate-specific-membrane-antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is a new whole body scanning technique that enables visualisation of prostate cancer with high sensitivity. The hypotheses of this study are that PSMA-PET/CT (a) has improved diagnostic accuracy compared to conventional imaging, (b) should be used as a first-line diagnostic test for staging, (c) the improved diagnostic accuracy will result in significant management impact and (d) provides economic benefits when incorporated into the management algorithm. Methods: This is a 300 patient phase III multi-centre randomized study of patients with untreated high-risk prostate cancer defined by Gleason grade group 3-5, PSA ≥ 20ng/ml or clinical stage ≥ T3. Patients are randomized to Gallium-68-PSMA11 PET/CT or conventional imaging, consisting of computer tomography of the abdomen/pelvis and bone scintigraphy with SPECT/CT. Patients with negative, equivocal or oligometastatic disease cross-over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT to conventional imaging for detecting nodal or distant metastatic disease. Accuracy is defined by a pre-defined “ground truth” scoring system incorporating histopathologic, imaging and clinical follow-up at six months post randomisation. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross-over, health economics, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. 294 of 300 (98%) patients randomised at time of abstract submission. Clinical trial information: 12617000005358.

scholarly journals Upfront metastasis-directed therapy in oligorecurrent prostate cancer does not decrease the time from initiation of androgen deprivation therapy to castration resistance

2021 ◽  
Vol 38 (6) ◽  
Author(s):  
Luca Triggiani ◽  
Rosario Mazzola ◽  
Davide Tomasini ◽  
Alessio Bruni ◽  
Giulia Alicino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Castration Resistance ◽  
Free Survival ◽  
Local Progression ◽  
Psma Pet ◽  
Pet Ct ◽  
Sensitive Phase

AbstractThe aim of the present study was to explore the potential impact of upfront metastases-directed therapy (MDT) in terms of prolongation of castration-sensitive phase in a series of oligorecurrent castration-sensitive prostate cancer (PC) patients. The present article is a multicenter retrospective study. The population of interest was castrate-sensitive oligorecurrent PC, defined as the presence of 1–3 uptakes in non-visceral sites such as bones or nodes detected by means of 18F-Choline PET/CT or 68-Gallium PSMA PET/CT. Primary endpoint was the time to castration resistance. Secondary endpoints were ADT-free survival, local progression-free survival, and overall survival. Eighty-two patients and 118 lesions were analyzed. The median time to castration resistance for the entire population of the study was 49 months (95% CI 43.6–54.4 months). The 1- and 2-year TTCR-free survival rates were 94% and 82%, respectively. At the time of analysis, 52 patients were still in the castration-sensitive phase of the disease. In this cohort of patients, the median ADT-free survival was 20 months (range 3–69 months). On the other hand, during follow-up 30 patients switched to the castration-resistant phase of disease. In this last group of patients, the median ADT-free survival was 20 months (range 4–50 months). After the ADT administration, the median castration-sensitive phase was 29 months (range 5–71 months). Castration resistance generally occurs at a median follow-up of 24–36 months following ADT. In the current study, upfront MDT does not decrease the time from initiation of ADT to castration resistance.

scholarly journals Penile secondary lesions: a rare entity detected by PET/CT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tima Davidson ◽  
Liran Domachevsky ◽  
Yogev Giladi ◽  
Eddie Fridman ◽  
Zohar Dotan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lesion Size ◽  
Focal Uptake ◽  
Psma Pet ◽  
Pet Ct ◽  
18F Fdg ◽  
Prostate Cancers ◽  
Disseminated Disease ◽  
Pet Scans

AbstractWhile penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identified by PET/CT. We reviewed 18F-FDG and Ga68-PSMA PET/CT records performed in a single center during May 2012-March 2020, for PSL. Of 16,774 18F-FDG and 1,963 Ga68-PSMA-PET scans, PSL were found in 24(0.13%) men with a mean age of 74. PSMA detected PSL in 12 with prostate cancer; FDG identified PSL in 4 with lymphoma, 3 with colorectal cancer, 2 with lung cancer, and one each with bladder cancer, pelvic sarcoma, and leukemia. Mean SUVmax of PSL was 7.9 ± 4.2 with focal uptake in 13(54%). Mean lesion size was 16.5 ± 6.8 mm; 8 at the penile root, 4 along the shaft, and 1 at the glans. CT detected loss of the penile texture in 15(63%). PSL were observed only during relapse or follow-up of disseminated disease. Among those with prostate cancer, PSA varied widely. Fifteen (62.5%) died, at a mean 13.3 ± 15.9 months following PSL demonstration, nine had non-prostate malignancies. PET/CT identified and characterized PSL in a fraction of cancer patients, most commonly those with prostate cancer. PSL universally surfaced in advanced disease, and signaled high mortality, especially in non-prostate cancers.

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.

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.

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