PSMA-negative prostate cancer and the continued value of choline-PET/CT

Alberts, Ian; Sachpekidis, Christos; Fech, Viktor; Rominger, Axel; Afshar‐Oromieh, Ali

doi:10.1055/a-1044-1855

Cited by 20 publications

(14 citation statements)

References 7 publications

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“…Finally, we wish to highlight the point that no PSMA-radiotracer has yet demonstrated a 100% sensitivity, and non PSMA-avid rPC is a potentially underreported phenomenon. No trial data is available for optimal imaging sequence in the scenario of PSMA-negative rPC, where additional PET/CT with choline can be of diagnostic benefit [53]. Finally, any future studies aspiring to inform evidence-based decision-making for PSMA-radiotracers should be designed in the context of existing evidence; this NMA provides valuable information about where studies with larger statistical precision are required and highlights which radiotracers should be compared in order to improve any future systematic network analysis [47] and where more multicentre studies might Funnel plot showing PET positivity rate (observed outcome) versus the standard error in the detection rate (p = 0.05) where the xaxis represents standard error and the y-axis detection rate, and each dot represents each study.…”

Section: Update Forestmentioning

confidence: 99%

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis

Alberts

Seide

Mingels

et al. 2021

Eur J Nucl Med Mol Imaging

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Purpose Numerous radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was to assess the detection rate of various radiotracers for the rPC. Methods The PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination. Results A majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network. Conclusion Differences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.

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Section: Update Forestmentioning

confidence: 99%

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis

Alberts

Seide

Mingels

et al. 2021

Eur J Nucl Med Mol Imaging

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“…False positives, such as rib fractures [ 20 ], and false negatives, such as PSMA-non avid metastases, have been reported [ 21 , 22 ]. Even at very high prostate-specific antigen (PSA) values, roughly 5% of PSMA-PET/CT scans are negative due to PSMA-negative disease, possibly as a result of tumour dedifferentiation [ 23 , 24 ]. Both anecdotal evidence and a retrospective cohort study confirm increased rates of non-specific tracer uptake in new generation tracers such as [ 18 F]PSMA-1007 when compared with [ 68 Ga]Ga-PSMA-11 [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

The influence of digital PET/CT on diagnostic certainty and interrater reliability in [68Ga]Ga-PSMA-11 PET/CT for recurrent prostate cancer

et al. 2021

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Objective To investigate the impact of digital PET/CT on diagnostic certainty, patient-based sensitivity and interrater reliability. Methods Four physicians retrospectively evaluated two matched cohorts of patients undergoing [68Ga]Ga-PSMA-11 PET/CT on a digital (dPET/CT n = 65) or an analogue scanner (aPET/CT n = 65) for recurrent prostate cancer between 11/2018 and 03/2019. The number of equivocal and pathological lesions as well as the frequency of discrepant findings and the interrater reliability for the two scanners were compared. Results dPET/CT detected more lesions than aPET/CT (p < 0.001). A higher number of pathological scans were observed for dPET/CT (83% vs. 57%, p < 0.001). The true-positive rate at follow-up was 100% for dPET/CT compared to 84% for aPET/CT (p < 0.001). The proportion of lesions rated as non-pathological as a total of all PSMA-avid lesions detected for dPET/CT was comparable to aPET/CT (61.8% vs. 57.0%, p = 0.99). Neither a higher rate of diagnostically uncertain lesions (11.5% dPET/CT vs. 13.7% aPET/CT, p = 0.95) nor discrepant scans (where one or more readers differed in opinion as to whether the scan is pathological) were observed (18% dPET/CT vs. 17% aPET/CT, p = 0.76). Interrater reliability for pathological lesions was excellent for both scanner types (Cronbach’s α = 0.923 dPET/CT; α = 0.948 aPET/CT) and interrater agreement was substantial for dPET/CT (Krippendorf’s α = 0.701) and almost perfect in aPET/CT (α = 0.802). Conclusions A higher detection rate for pathological lesions for dPET/CT compared with aPET/CT in multiple readers was observed. This improved sensitivity was coupled with an improved true-positive rate and was not associated with increased diagnostic uncertainty, rate of non-specific lesions, or reduced interrater reliability. Key Points • New generation digital scanners detect more cancer lesions in men with prostate cancer. • When using digital scanners, the doctors are able to diagnose prostate cancer lesions with better certainty • When using digital scanners, the doctors do not disagree with each other more than with other scanner types.

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“…There was a lack of histopathological evidence indicative of PC or other in ammatory or neoplastic processes suggestive of a non-PC malignancy. Although PSMA-negative PC can occur in a minority of patients [23], this cannot explain the discordance between PSMA PET/CT and IHC ndings and points toward an as yet unclari ed issue with the radiopharmaceutical. Noting the abundance of reports of UBL and cognisant of their potential adverse clinical impact, further studies are necessary to understand better this phenomenon and the limitations of this tracer.…”

Section: Discussionmentioning

confidence: 90%

Assessment of Malignancy and PSMA-expression of Uncertain Bone Lesions in [18F]PSMA-1007 PET/CT for Prostate Cancer- a Single Centre Experience of PET-guided Biopsies

Afshar‐Oromieh

Vollnberg

Alberts

et al. 2022

Preprint

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Purpose: Uncertain bone lesions (UBL) with intensive radiopharmaceutical avidity are frequently observed in patients undergoing [18F]PSMA-1007 PET/CT for the detection of prostate cancer (PC). Such lesions can pose diagnostic conundrums and risk an incorrect staging. The aim of this short communication is to share the results of PET-guided biopsies of such lesions. Methods: A retrospective analysis revealed 10 patients who were referred to our department for PET-guided biopsy of UBL visible in a previous [18F]PSMA-1007 PET/CT. [18F]-PSMA-1007 PET-guided biopsy was conducted for 11 PSMA-avid bone lesions in these 10 patients. The biopsy materials were analysed for tissue typing and immunohistochemistry (IHC) was performed for prostate-specific-membrane-antigen (PSMA) expression. The scans were analysed by two experienced physicians in a consensus read for clinical characteristics and radiopharmaceutical uptake of lesions. Results: 1/11 (9.1%) of the lesions biopsied was confirmed as bone metastasis of PC with intense PSMA-expression while 10/11 (90.9%) lesions were revealed to be unremarkable bone tissue without evidence of PSMA-expression at IHC. Amongst all bone lesions assessed by biopsy, eight were visually classified as being at high risk of malignancy in the PET/CT (SUVmean 12.0 ± 8.1; SUVmax 18.8 ± 13.1), three as equivocal (SUVmean 4.6 ± 2.1; SUVmax 7.2 ± 3.0) and zero as low risk. No UBL had any CT correlate. Conclusions: In this cohort biopsy revealed that a small but relevant number of UBL are true metastases. For those confirmed as benign, no PSMA-expression at IHC was observed, suggesting a non-PSMA mediated cause for intensive [18F]PSMA-1007-uptake of which the reason remains unclear. Readers must interpret such lesions with caution in order to reduce the risk of erroneous staging and subsequent treatment. PET-guided biopsy, particularly in the absence of morphological changes in the CT, can be a useful method to clarify such lesions.

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PSMA-negative prostate cancer and the continued value of choline-PET/CT

Cited by 20 publications

References 7 publications

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis

The influence of digital PET/CT on diagnostic certainty and interrater reliability in [68Ga]Ga-PSMA-11 PET/CT for recurrent prostate cancer

Assessment of Malignancy and PSMA-expression of Uncertain Bone Lesions in [18F]PSMA-1007 PET/CT for Prostate Cancer- a Single Centre Experience of PET-guided Biopsies

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