Rationale
The development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in ...clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions.
Methods
A panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process.
Results
According to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET.
Conclusions
The E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.
The aim of this guideline is to provide standards for the recommendation, performance, interpretation and reporting of
68
Ga-PSMA PET/CT for prostate cancer imaging. These recommendations will help ...to improve accuracy, precision, and repeatability of
68
Ga-PSMA PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.
We aimed to review the current state‐of‐the‐art imaging methods used for primary and secondary staging of prostate cancer, mainly focusing on multiparametric magnetic resonance imaging and ...positron‐emission tomography/computed tomography with new radiotracers. An expert panel of urologists, radiologists and nuclear medicine physicians with wide experience in prostate cancer led a PubMed/MEDLINE search for prospective, retrospective original research, systematic review, meta‐analyses and clinical guidelines for local and systemic staging of the primary tumor and recurrence disease after treatment. Despite magnetic resonance imaging having low sensitivity for microscopic extracapsular extension, it is now a mainstay of prostate cancer diagnosis and local staging, and is becoming a crucial tool in treatment planning. Cross‐sectional imaging for nodal staging, such as computed tomography and magnetic resonance imaging, is clinically useless even in high‐risk patients, but is still suggested by current clinical guidelines. Positron‐emission tomography/computed tomography with newer tracers has some advantage over conventional images, but is not cost‐effective. Bone scan and computed tomography are often useless in early biochemical relapse, when salvage treatments are potentially curative. New imaging modalities, such as prostate‐specific membrane antigen positron‐emission tomography/computed tomography and whole‐body magnetic resonance imaging, are showing promising results for early local and systemic detection. Newer imaging techniques, such as multiparametric magnetic resonance imaging, whole‐body magnetic resonance imaging and positron‐emission tomography/computed tomography with prostate‐specific membrane antigen, have the potential to fill the historical limitations of conventional imaging methods in some clinical situations of primary and secondary staging of prostate cancer.
In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its ...higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, PSMA was studied as a therapeutic agent targeted with various isotopes. In 2021, results from the VISION trial led to the Food and Drug Administration (FDA) approval of
LuLu-PSMA-617 as a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) and set the basis for a radical change in the future perspectives of PCa treatment and the history of Nuclear Medicine. Despite these promising results, primary resistance in patients treated with single-agent
LuLu-PSMA-617 remains a real issue. Emerging trials are investigating the use of
LuLu-PSMA-617 in combination with other PCa therapies in order to cover the multiple oncologic resistance pathways and to overcome tumor heterogeneity. In this review, our aim is to retrace the history of PSMA-targeted therapy from the first preclinical studies to its future applications in PCa.
The tumor microenvironment (TME) surrounding tumor cells is a complex and highly dynamic system that promotes tumorigenesis. Cancer-associated fibroblasts (CAFs) are key elements in TME playing a ...pivotal role in cancer cells' proliferation and metastatic spreading. Considering the high expression of the fibroblast activation protein (FAP) on the cell membrane, CAFs emerged as appealing TME targets, namely for molecular imaging, leading to a pan-tumoral approach. Therefore, FAP inhibitors (FAPis) have recently been developed for PET imaging and radioligand therapy, exploring the clinical application in different tumor sub-types. The present review aimed to describe recent developments regarding radiolabeled FAP inhibitors and evaluate the possible translation of this pan-tumoral approach in clinical practice. At present, the application of FAPi-PET has been explored mainly in single-center studies, generally performed in small and heterogeneous cohorts of oncological patients. However, preliminary results were promising, in particular in low FDG-avid tumors, such as primary liver and gastro-entero-pancreatic cancer, or in regions with an unfavorable tumor-to-background ratio at FDG-PET/CT (i.e., brain), and in radiotherapy planning of head and neck tumors. Further promising results have been obtained in the detection of peritoneal carcinomatosis, especially in ovarian and gastric cancer. Data regarding the theranostics approach are still limited at present, and definitive conclusions about its efficacy cannot be drawn at present. Nevertheless, the use of FAPi-based radio-ligand to treat the TME has been evaluated in first-in-human studies and appears feasible. Although the pan-tumoral approach in molecular imaging showed promising results, its real impact in day-to-day clinical practice has yet to be confirmed, and multi-center prospective studies powered for efficacy are needed.
Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is currently recommended to restage prostate cancer (PCa) and to guide the delivery of salvage treatments. We ...aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. Methods: 324 hormone-sensitive PCa with PSA relapse after radical prostatectomy who underwent PSMA-PET in three high-volume European Centres. Patients have been stratified as pre-salvage who never received salvage treatments (n = 134), and post-salvage, including patients who received previous salvage therapies (n = 190). Patients with oligorecurrent (≤3 lesions), PSMA-positive disease underwent PSMA-directed treatments: salvage radiotherapy (sRT) or Metastases-directed therapy (MDT). Patients with polirecurrent (>3 lesions) PSMA-positive disease were treated with systemic therapy. Patients with negative PSMA-PET were treated with sRT or systemic therapies or observation. The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were: Metastases-free survival (MFS) and Castration Resistant Pca free survival (CRPC-FS). Results: median follow up was 23 months. In the pre-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 66.2% vs. 38.9%, 95.2% vs. 73.7% and 94.9% vs. 93.1% in patients with negative vs. positive PSMA-PET, respectively (all p ≥ 0.2). In the post-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 59.5% vs. 29.1%, 92.7% vs. 65.1% and 98.8% vs. 88.8% in patients with negative vs. positive PSMA-PET, respectively (all p ≤ 0.01). At multivariable analyses, a positive PSMA-PET was an independent predictor of progression (HR = 2.15) and metastatic disease (HR 2.37; all p ≤ 0.03). Conclusion: PSMA-PET in recurrent PCa detects the site of recurrence guiding salvage treatments and has a prognostic role in patients who received previous salvage treatments.
Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the ...oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients.
we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy ADT). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease.
Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (
= 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all
≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%;
= 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all
≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.
Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for ...both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics.
MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building.
Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients.
The study was prospectively registered at clinicaltrials.gov (NCT05974475).
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