Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging

Sheikhbahaei, Sara; Afshar‐Oromieh, Ali; Eiber, Matthias; Solnes, Lilja B.; Javadi, Mehrbod S.; Ross, Ashley E.; Pienta, Kenneth J.; Allaf, Mohamad E.; Haberkorn, Uwe; Pomper, Martin G.; Gorin, Michael A.; Rowe, Steven P.

doi:10.1007/s00259-017-3780-7

Cited by 250 publications

(231 citation statements)

References 172 publications

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“…CT and MRI abnormalities such as regional grouping, loss of fatty hilum, or focal necrosis may serve as additional morphologic criteria. PSMA-ligand-positive pitfalls such as focal uptake in the celiac ganglia or an adjacent ureter, inflammation, or lymphedema must be ruled out (7,25,50,51).…”

Section: Pelvic Nodes (N)mentioning

confidence: 99%

Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT

et al. 2017

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See an invited perspective on this article on page 466. Prostate-specific membrane antigen (PSMA)-ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.

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Section: Pelvic Nodes (N)mentioning

confidence: 99%

Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT

et al. 2017

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“…Note that these findings are the most challenging. Here often further work-up is necessary, e.g., follow-up imaging, additional imaging like MRI, or even biopsy also used by other groups in recent studies [15,22,23]. For the analysis of detection rates, categories 4 and 5 were considered "positive for malignancy" and 1-3 as "negative."…”

Section: Image Analysismentioning

confidence: 99%

Interobserver variability, detection rate, and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy

Miksch

Bottke

Krohn

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose 68 Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an individualized radiotherapy concept. However, subtle findings especially concerning small local recurrences can still be challenging to interpret and are prone to variability between different readers. Thus, we analyzed interobserver variability, detection rate, and lesion patterns systematically in a homogeneous patient population with low-level biochemical recurrence. Methods We analyzed 68 Ga-PSMA-11-PET/CTs in 116 patients with status post-prostatectomy and PSA levels up to 0.6 ng/ml. None of them received ADT or radiotherapy beforehand. Images were interpreted and blinded by two nuclear medicine physicians (R1 and R2). Findings were rated using a 5-point scale concerning local recurrence, lymph nodes, bone lesions, and other findings (1: definitely benign, 2: probably benign, 3: equivocal, 4: probably malignant, 5: definitely malignant). In findings with substantial discrepancies of 2 or more categories and/or potentially leading to differences in further patient management, a consensus reading was done with a third reader (R3). Interobserver agreement was measured by Cohens Kappa analysis after sub-categorizing our classification system to benign (1 + 2), equivocal (3), and malignant (4 + 5). Time course of PSA levels after salvage treatment of patients rated as positive (4 + 5) was analyzed. Results The overall detection rate (categories 4 and 5) was 50% (R1/R2, 49%/51%) and in the PSA subgroups 0-0.2 ng/ml, 0.21-0.3 ng/ml, and 0.31-0.6 ng/ml 24%/27%, 57%/57%, and 65%/68%, respectively. Local recurrence was the most common lesion manifestation followed by lymphatic and bone metastases. The overall agreement in the Cohens Kappa analysis was 0.74 between R1 and R2. For local, lymphatic, and bone sites, the agreement was 0.76, 0.73, and 0.58, respectively. PSA levels of PSMA PET/CT-positive patients after salvage treatment decreased in 75% (27/36) and increased in 25% (9/36). A decrease of PSA, although more frequent in patients with imaging suggesting only local tumor recurrence (86%, 18/21), was also observed in 67% (10/15) of patients with findings of metastatic disease. Conclusions In a highly homogeneous group of prostate cancer patients with early-stage biochemical recurrence after radical prostatectomy, we could show that 68 Ga-PSMA-11-PET/CT has a good detection rate of 50% which is in accordance with literature, with clinically relevant findings even in patients with PSA < 0.21 ng/ml. The interobserver variability is low, particularly concerning assessment of local recurrences and lymph nodes. Therefore, PSMA-PET/CT is a robust diagnostic modality in this patient group for therapy planning.Jonathan Miksch and Dirk Bottke are shared first authors.

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“…A preliminary analysis of sequential 68 Ga-PSMA-11 PET testing in 23 metastatic PCa patients before and after multiple cycles of docetaxel showed that such testing may outperform conventional CT imaging for treatment response, although the differences were not statistically significant 20. PSMA imaging routinely outperforms conventional bone scans and CT, and thus CTC-based PSMA testing may decrease the possibility of false negatives on scans as benign lesions have rarely been associated with PSMA radiotracer uptake 21. The present analysis is limited by the inclusion of a heterogeneous patient population undergoing a broad array of different treatments rather than a specific homogeneous population.…”

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A pilot study of prostate‐specific membrane antigen (PSMA) dynamics in men undergoing treatment for advanced prostate cancer

et al. 2019

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Background Prostate‐specific membrane antigen (PSMA) is a rational target for noninvasive detection of recurrent prostate cancer (PCa) and for therapy of metastatic castration‐resistant prostate cancer (mCRPC) with PSMA‐targeted agents. Here we conducted serial measurements of PSMA expression on circulating tumor cells (CTCs) to evaluate patterns of longitudinal PSMA dynamics over the course of multiple sequential therapies. Methods A retrospective investigation of men with mCRPC undergoing evaluation at medical oncology clinics at our institution assessed the dynamics of PSMA expression in the context of different systemic treatments administered sequentially. Eligibility included patients who began systemic therapies with androgen receptor (AR)‐directed agents or taxane agents for whom peripheral blood samples were tested for CTC mRNA of AR splice variant‐7 (AR‐V7), prostate‐specific antigen (PSA), and PSMA (with >2 CTC + results) in a CLIA‐accredited laboratory. Results From August 2015 to November 2017, we identified 96 eligible men. Fifteen had greater than or equal to 2 sequential therapies and evaluable CTC samples, greater than or equal to 1 expressing PSMA (PSMA+). Among the 15 patients included in this analysis, a total of 54 PSMA status evaluations were performed in the context of 48 therapies during a median follow‐up of 18 months. At baseline, PSMA signal was detected (“positive”) in 11 of 15 (73.3%) patients, while for 4 of 15 (26.7%) patients PSMA signal was undetectable (“negative”). In all but two patients, the baseline collection corresponded with a change in treatment. On the second assessment, PSMA increases were detected in all 4/4 (100%) PSMA‐negative patients and 8 of 11 (72.7%) PSMA‐positive patients. PSMA significantly decreased in a patient treated with 177Lu‐PSMA‐617. Serum PSA declines were seen in 7 of 8 (88%) of the treatment periods where PSMA decreased. Conclusions PSMA expression in CTCs is a dynamic marker. PSMA transcript declines appear to be associated with concurrent decreases in serum PSA. Sequential CTC sampling could provide a noninvasive response assessment to systemic treatment for mCRPC.

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Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging

Abstract: As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance.

Cited by 250 publications

References 172 publications

Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT

Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT

Interobserver variability, detection rate, and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy

A pilot study of prostate‐specific membrane antigen (PSMA) dynamics in men undergoing treatment for advanced prostate cancer

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