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Current Use of PSMA in Prostate Cancer Treatment
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Current Use of PSMA in Prostate Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 16567

Special Issue Editors

Prof. Dr. Jukka Kemppainen

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Guest Editor
Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland
Interests: molecular cancer PET imaging; radionuclide therapy; prostate cancer
Prof. Dr. Samer Ezziddin

E-Mail Website
Guest Editor
Department of Nuclear Medicine, Saarland University Medical Center, 66421 Homburg, Germany
Interests: radionuclide therapy; PET-CT; molecular imaging

Special Issue Information

Dear Colleagues,

Prostate specific membrane antigen (PSMA) targeted prostate cancer (PCa) PET -imaging has rapidly replaced other prostate cancer targeted PET imaging tracers. With this more sensitive tracer the location of disease activation can be shown with significantly lower PSA values in patients with disease recurrence. PSMA targeted imaging appears to be very sensitive method for detecting lymph node and bone metastases also in initial staging changing the management of many patients.

In the light of recent data, replacing traditional bone scan and abdominopelvic computed tomography (CT) by more sensitive PSMA PET-imaging might be considered especially in patient with high-risk patients although it is not currently known whether this approach also has impact on patient outcome. While PSMA PET imaging is very sensitive method in detecting prostate cancer metastases and it has in general good positive and negative predictive value, it is challenged by detection sensitivity of small lymph node metastases and false positive bone activity.

PSMA targeted imaging has also brought theragnostic approach to PCa treatment with beta and alfa emitting 177Lu- or 225Ac-PSMA targeted therapy. Initial outcome data from177Lu-PSMA treatment of castration resistant PCa is very promising. Currently it is not known how to optimally choose the patients who benefit most from radionuclide therapy and whether better outcome would be gained if radionuclide therapy is provided already in castration sensitive disease phase.

The aim of this special issue is to focus in the Current use of PSMA -targeted imaging in Prostate Cancer Treatment to provide insight what is hot and currently cooking in staging, re-staging, therapy assessment, Theranostics, tracer development, radiomics and artificial intelligence research in this field.

Prof. Dr. Jukka Kemppainen
Prof. Dr. Samer Ezziddin
Guest Editors

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Published Papers (6 papers)

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Research

15 pages, 2422 KiB  
Article
Tumor Sink Effect with Prostate-Specific Membrane Antigen-Targeted Theranostics in Patients with Metastatic Castration-Resistant Prostate Cancer: Intra-Individual Evaluations
by Caroline Burgard, Florian Rosar, Robert J. Marlowe, Mark Bartholomä, Sebastian Dewes, Andrea Schaefer-Schuler, Johannes Linxweiler, Fadi Khreish and Samer Ezziddin
Cancers 2023, 15(9), 2592; https://doi.org/10.3390/cancers15092592 - 3 May 2023
Cited by 6 | Viewed by 2743
Abstract
“Tumor sink effects”, decreased physiological uptake of radiopharmaceuticals due to sequestration by a tumor, may impact radioligand therapy (RLT) toxicity and dosing. We investigated these effects with prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals in the healthy organs-at-risk (the parotid glands, kidneys, liver, and spleen) [...] Read more.
“Tumor sink effects”, decreased physiological uptake of radiopharmaceuticals due to sequestration by a tumor, may impact radioligand therapy (RLT) toxicity and dosing. We investigated these effects with prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals in the healthy organs-at-risk (the parotid glands, kidneys, liver, and spleen) of 33 patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively performed three intra-individual comparisons. First, we correlated changes from baseline to post-RLT (after two 177-lutetium (177Lu)-PSMA-617 cycles) in total lesional PSMA (∆TLP) and organ mean standardized uptake values (∆SUVmean). Second, in 25 RLT responders, we compared the organ SUVmean post-RLT versus that at baseline. Lastly, we correlated the baseline TLP and organ SUVmean. Data were acquired via 68-gallium-PSMA-11 positron emission tomography before the first and after the second 177Lu-PSMA-617 cycle. In the parotid glands and spleen, ∆TLP and ∆SUVmean showed a significant inverse correlation (r = −0.40, p = 0.023 and r = −0.36, p = 0.042, respectively). Additionally, in those tissues, the median organ SUVmean rose significantly from baseline after the response to RLT (p ≤ 0.022), and the baseline TLP and SUVmean were significantly negatively correlated (r = −0.44, p = 0.01 and r = −0.42, p = 0.016, respectively). These observations suggest tumor sink effects with PSMA-targeted radiopharmaceuticals in the salivary glands and spleen of patients with mCRPC. Full article
(This article belongs to the Special Issue Current Use of PSMA in Prostate Cancer Treatment)
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11 pages, 1216 KiB  
Article
PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study
by Amina Banda, Bastiaan M. Privé, Youssra Allach, Maike J. M. Uijen, Steffie M. B. Peters, Cato C. Loeff, Martin Gotthardt, Constantijn H. J. Muselaers, J. Alfred Witjes, Inge M. van Oort, J. P. Michiel Sedelaar, Harm Westdorp, Niven Mehra, Fadi Khreish, Samer Ezziddin, Amir Sabet, Michael C. Kreissl, Thomas Winkens, Philipp Seifert, Marcel J. R. Janssen, Willemijn A. M. van Gemert and James Nagarajahadd Show full author list remove Hide full author list
Cancers 2023, 15(1), 297; https://doi.org/10.3390/cancers15010297 - 31 Dec 2022
Cited by 11 | Viewed by 3490
Abstract
Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [ [...] Read more.
Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up. Full article
(This article belongs to the Special Issue Current Use of PSMA in Prostate Cancer Treatment)
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15 pages, 1476 KiB  
Article
Single Center Experience with a 4-Week 177Lu-PSMA-617 Treatment Interval in Patients with Metastatic Castration-Resistant Prostate Cancer
by Jukka Kemppainen, Aki Kangasmäki, Simona Malaspina, Bernd Pape, Jarno Jalomäki, Kalevi Kairemo, Juha Kononen and Timo Joensuu
Cancers 2022, 14(24), 6155; https://doi.org/10.3390/cancers14246155 - 14 Dec 2022
Cited by 3 | Viewed by 2468
Abstract
Background: 177Lu-PSMA-617 is a promising theragnostic treatment for metastatic castration-resistant prostate cancer (mCRPC). However, both the optimal treatment dose and interval in mCRPC and the rate of identification of responders from non-responders among possible treatment candidates are unknown. Methods: 62 men with [...] Read more.
Background: 177Lu-PSMA-617 is a promising theragnostic treatment for metastatic castration-resistant prostate cancer (mCRPC). However, both the optimal treatment dose and interval in mCRPC and the rate of identification of responders from non-responders among possible treatment candidates are unknown. Methods: 62 men with mCRPC who were treated with 177Lu-PSMA-617 during 1/2017–2/2019 were included in the study. Treatment responses, overall survival (OS) and progression free survival (PFS) were determined. The median follow-up time was 1.4 years (IQR 0.5–2.2). Tumor volume of metastases (MTV), SUVmax and tumor lesion activity (TLA) were quantitated from pre-treatment PSMA PET/CT images together with pre-treatment PSA. Results: An average of three treatment cycles (2–5) were given within a four-week interval. PFS was 4.9 months (2.4–9.6) and OS was 17.2 months (6–26.4). There were no major adverse events reported. A significant PSA response of >50% was found in 58.7% of patients, which was significantly associated with longer OS, p < 0.004. PSA response was not associated with staging PSMA-derived parameters. Conclusions: 177Lu-PSMA-617 treatment in four-week intervals was safe and effective. Almost 60% of patients had a significant PSA response, which was associated with better OS. Pre-treatment PSA kinetics or staging PSMA PET/CT-derived parameters were not helpful in identifying treatment responders from non-responders; better biomarkers are needed to aid in patient selection. Full article
(This article belongs to the Special Issue Current Use of PSMA in Prostate Cancer Treatment)
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8 pages, 227 KiB  
Article
Distant Nodes Seen on PSMA PET-CT Staging Predicts Post-Treatment Progression in Men with Newly Diagnosed Prostate Cancer—A Prospective Cohort Study
by Sean Ong, Claire Pascoe, Brian D. Kelly, Zita Ballok, David Webb, Damien Bolton, Declan Murphy, Shomik Sengupta, Patrick Bowden and Nathan Lawrentschuk
Cancers 2022, 14(24), 6134; https://doi.org/10.3390/cancers14246134 - 13 Dec 2022
Viewed by 1538
Abstract
PSMA PET-CT scans are now recommended in international urological guidelines for primary staging and re-staging of prostate cancer. However, there is little published literature on the clinical outcomes for patients after treatment decisions made using PSMA PET-CT results. This is a multisite, prospective [...] Read more.
PSMA PET-CT scans are now recommended in international urological guidelines for primary staging and re-staging of prostate cancer. However, there is little published literature on the clinical outcomes for patients after treatment decisions made using PSMA PET-CT results. This is a multisite, prospective cohort study investigating the clinical outcomes of men who received treatment plans based on PSMA PET-CT results for primary staging. Men with biopsy proven prostate cancer received a PSMA PET-CT scan for primary staging. Treatment plans were recommended by multidisciplinary teams (MDT). After treatment, these men were followed with 6 monthly PSA tests and imaging or biopsies if recommended by MDT. The primary outcome was treatment progression defined as the addition or change of any treatment modalities such as androgen deprivation therapy, radiation therapy or chemotherapy. In total, 80% of men did not have any treatment progression after enactment of treatment based on PSMA PET-CT primary staging results at 29 months of follow up. Men who had distant nodes seen on PSMA PET-CT had a 5 times increased risk of treatment progression. Larger studies with longer follow up are needed to validate our results and optimise the way clinicians use PSMA PET-CT results to guide management. Full article
(This article belongs to the Special Issue Current Use of PSMA in Prostate Cancer Treatment)
13 pages, 4620 KiB  
Article
Dose-Escalated Salvage Radiotherapy for Macroscopic Local Recurrence of Prostate Cancer in the Prostate-Specific Membrane Antigen Positron Emission Tomography Era
by Jörg Tamihardja, Leonie Zehner, Philipp E. Hartrampf, Sinan Cirsi, Sonja Wegener, Andreas K. Buck, Michael Flentje and Bülent Polat
Cancers 2022, 14(19), 4956; https://doi.org/10.3390/cancers14194956 - 10 Oct 2022
Cited by 4 | Viewed by 1957
Abstract
Background: The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Methods: Between February 2010 and June 2021, 367 patients received SRT after radical [...] Read more.
Background: The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Methods: Between February 2010 and June 2021, 367 patients received SRT after radical prostatectomy. Out of the 367 screened patients, 111 patients were staged by PSMA PET/CT before SRT. A total of 59 out of these 111 (53.2%) patients were treated for PSMA PET-positive macroscopic prostatic fossa recurrence. Dose-escalated SRT was applied with a simultaneous integrated boost at a median prescribed dose of 69.3 Gy (IQR 69.3–72.6 Gy). The oncological outcome was investigated using Kaplan-Meier and Cox regression analyses. The genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (version 5.0). Results: The median follow-up was 38.2 months. The three-year biochemical progression-free survival rate was 89.1% (95% CI: 81.1–97.8%) and the three-year metastasis-free survival rate reached 96.2% (95% CI: 91.2–100.0%). The cumulative three-year late grade 3 GU toxicity rate was 3.4%. No late grade 3 GI toxicity occurred. Conclusions: Dose-escalated PSMA PET/CT-guided salvage radiotherapy for macroscopic prostatic fossa recurrence resulted in favorable survival and toxicity rates. Full article
(This article belongs to the Special Issue Current Use of PSMA in Prostate Cancer Treatment)
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9 pages, 241 KiB  
Article
PSMA PET-CT Imaging Predicts Treatment Progression in Men with Biochemically Recurrent Prostate Cancer—A Prospective Study of Men with 3 Year Follow Up
by Sean Ong, Claire Pascoe, Brian D. Kelly, Zita Ballok, David Webb, Damien Bolton, Declan Murphy, Shomik Sengupta, Patrick Bowden and Nathan Lawrentschuk
Cancers 2022, 14(11), 2717; https://doi.org/10.3390/cancers14112717 - 31 May 2022
Cited by 7 | Viewed by 2975
Abstract
Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims [...] Read more.
Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims to assess the clinical impact of PSMA PET-CT by analyzing its predictive value of treatment progression after 3 years of follow-up. In this prospective cohort study of 100 men, patients received a PSMA PET-CT for restaging of their disease which was used by a multi-disciplinary team to make a treatment decision. The primary endpoint was treatment progression. This was defined as the addition or change of any treatment modalities such as androgen deprivation therapy (ADT), radiation therapy or chemotherapy. The median follow-up time was 36 months (IQR 24–40 months). No treatment progression was found in 72 (75%) men and therefore 24 (25%) patients were found to have treatment progression. In men with a negative PSMA PET-CT result, 5/33 (15.1%) had treatment progression and 28/33 (84.8%) had no treatment progression. In conclusion, clinical decisions made with PSMA PET-CT results led to 75% of men having no treatment progression at 3 years of follow-up. In men with negative PSMA PET-CT results, this increased to 85% of men. Full article
(This article belongs to the Special Issue Current Use of PSMA in Prostate Cancer Treatment)
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