68 Ga-PSMA Cerenkov luminescence imaging in primary prostate cancer: first-in-man series

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Abstract

Purpose

Currently, approximately 11–38% of prostate cancer (PCa) patients undergoing radical prostatectomy have a positive surgical margin (PSM) on histopathology. Cerenkov luminescence imaging (CLI) using ⁶⁸Ga-prostate-specific membrane antigen ( ⁶⁸Ga-PSMA) is a novel technique for intraoperative margin assessment. The aim of this first-in-man study was to investigate the feasibility of intraoperative ⁶⁸Ga-PSMA CLI . In this study, feasibility was defined as the ability to distinguish between a positive and negative surgical margin, imaging within 45 min and low radiation exposure to staff.

Methods

Six patients were included in this ongoing study. Following perioperative i.v. injection of ~ 100 MBq ⁶⁸Ga-PSMA, the prostate was excised and immediately imaged ex vivo. Different acquisition protocols were tested, and hotspots on CLI images from the intact prostate were marked for comparison with histopathology.

Results

By using an acquisition protocol with 150 s exposure time, 8 × 8 binning and a 550 nm shortpass filter, PSMs and negative surgical margins (NSMs) were visually correctly identified on CLI in 3 of the 5 patients. Two patients had a hotspot on CLI from cancer < 0.1 mm from the excision margin.

Conclusion

Overall, the study showed that ⁶⁸Ga-PSMA CLI is a feasible and low-risk technique for intraoperative margin assessment in PCa. The remaining patients in this ongoing study will be used to assess the diagnostic accuracy of the technique.

Trial registration: NL8256 registered at www.trialregister.nl on 04/11/20109.

Related collections

Most cited references 22

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Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911).

Michel Bolla, Hein Van Poppel, Bertrand Tombal … (2012)

We report the long-term results of a trial of immediate postoperative irradiation versus a wait-and-see policy in patients with prostate cancer extending beyond the prostate, to confirm whether previously reported progression-free survival was sustained. This randomised, phase 3, controlled trial recruited patients aged 75 years or younger with untreated cT0-3 prostate cancer (WHO performance status 0 or 1) from 37 institutions across Europe. Eligible patients were randomly assigned centrally (1:1) to postoperative irradiation (60 Gy of conventional irradiation to the surgical bed for 6 weeks) or to a wait-and-see policy until biochemical progression (increase in prostate-specific antigen >0·2 μg/L confirmed twice at least 2 weeks apart). We analysed the primary endpoint, biochemical progression-free survival, by intention to treat (two-sided test for difference at α=0.05, adjusted for one interim analysis) and did exploratory analyses of heterogeneity of effect. This trial is registered with ClinicalTrials.gov, number NCT00002511. 1005 patients were randomly assigned to a wait-and-see policy (n=503) or postoperative irradiation (n=502) and were followed up for a median of 10·6 years (range 2 months to 16·6 years). Postoperative irradiation significantly improved biochemical progression-free survival compared with the wait-and-see policy (198 [39·4%] of 502 patients in postoperative irradiation group vs 311 [61·8%] of 503 patients in wait-and-see group had biochemical or clinical progression or died; HR 0·49 [95% CI 0·41-0·59]; p<0·0001). Late adverse effects (any type of any grade) were more frequent in the postoperative irradiation group than in the wait-and-see group (10 year cumulative incidence 70·8% [66·6-75·0] vs 59·7% [55·3-64·1]; p=0.001). Results at median follow-up of 10·6 years show that conventional postoperative irradiation significantly improves biochemical progression-free survival and local control compared with a wait-and-see policy, supporting results at 5 year follow-up; however, improvements in clinical progression-free survival were not maintained. Exploratory analyses suggest that postoperative irradiation might improve clinical progression-free survival in patients younger than 70 years and in those with positive surgical margins, but could have a detrimental effect in patients aged 70 years or older. Ligue Nationale contre le Cancer (Comité de l'Isère, Grenoble, France) and the European Organisation for Research and Treatment of Cancer (EORTC) Charitable Trust. Copyright © 2012 Elsevier Ltd. All rights reserved.

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Positive surgical margins after radical prostatectomy: a systematic review and contemporary update.

James Eastham, Alberto Briganti, Jonathan H. Epstein … (2014)

The clinical significance of positive surgical margins (PSMs) in radical prostatectomy (RP) specimens and the management of affected patients remain unclear. To address pitfalls in the pathologic interpretation of margin status; provide an update on the incidence, predictors, and long-term oncologic implications of PSMs in the era of robot-assisted laparoscopic RP (RALRP); and suggest a practical evidence-based approach to patient management. A systematic review of the literature was performed in April 2013 using Medline/PubMed, Web of Science, and Scopus databases and the Cochrane Database of Systematic Reviews. Studies focusing on PSMs in RP pertinent to the objectives of this review were included. Particular attention was paid to publications within the last 5 yr and those concerning RALRP. A total of 74 publications were retrieved. Standardized measures to overcome variability in the pathologic interpretation of surgical margins have recently been established by the International Society of Urological Pathology. The average rate of PSMs in contemporary RALRP series is 15% (range: 6.5-32%), which is higher in men with a more advanced pathologic stage and equivalent to the rate reported in prior open and laparoscopic prostatectomy series. The likelihood of PSMs is strongly influenced by the surgeon's experience irrespective of the surgical approach. Technical modifications using the robotic platform and the role of frozen-section analysis to reduce the margin positivity rate continue to evolve. Positive margins are associated with a twofold increased hazard of biochemical relapse, but their association with more robust clinical end points is controversial. Level 1 evidence suggests that adjuvant radiation therapy (RT) may favorably affect prostate-specific antigen recurrence rates, but whether the therapy also affects systemic progression, prostate cancer-specific mortality, and overall survival remains debatable. Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers. Adjuvant RT appears to be effective, but further study is required to determine whether early salvage RT is an equivalent alternative. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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Fundamental Limits of Spatial Resolution in PET.

William W Moses (2011)

The fundamental limits of spatial resolution in positron emission tomography (PET) have been understood for many years. The physical size of the detector element usually plays the dominant role in determining resolution, but the combined contributions from acollinearity, positron range, penetration into the detector ring, and decoding errors in the detector modules often combine to be of similar size. In addition, the sampling geometry and statistical noise further degrade the effective resolution. This paper describes quantitatively describes these effects, discusses potential methods for reducing the magnitude of these effects, and computes the ultimately achievable spatial resolution for clinical and pre-clinical PET cameras.

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Author and article information

Contributors

Judith olde Heuvel: j.olde.heuvel@nki.nl

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur. J. Nucl. Med. Mol. Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 2 April 2020

Publication date PMC-release: 2 April 2020

Publication date (Print): 2020

Volume: 47

Issue: 11

Pages: 2624-2632

Affiliations

[1 ]GRID grid.430814.a, Department of Nuclear Medicine, , Netherlands Cancer Institute-Antoni van Leeuwenhoek, ; Amsterdam, The Netherlands

[2 ]GRID grid.6214.1, ISNI 0000 0004 0399 8953, Technical Medicine Center, , University of Twente, ; Enschede, Netherlands

[3 ]GRID grid.430814.a, Department of Urology, , Netherlands Cancer Institute-Antoni van Leeuwenhoek, ; Amsterdam, Netherlands

[4 ]GRID grid.430814.a, Department of Pathology, , Netherlands Cancer Institute-Antoni van Leeuwenhoek, ; Amsterdam, Netherlands

[5 ]GRID grid.435758.8, Lightpoint Medical Ltd., ; Chesham, UK

Article

Publisher ID: 4783

DOI: 10.1007/s00259-020-04783-1

PMC ID: 7515945

PubMed ID: 32242253

SO-VID: 2d87f8ec-c053-4183-a50a-cb85c3460552

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 14 November 2019

Date accepted : 19 March 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100004622, KWF Kankerbestrijding;

Award ID: 15175

Award Recipient : Marcel P. M. Stokkel

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: cerenkov imaging,68-gallium-psma intraoperative assessment,positive surgical margin,primary prostate cancer

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: cerenkov imaging, 68-gallium-psma intraoperative assessment, positive surgical margin, primary prostate cancer