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      The prognostic power of 18F-FDG PET/CT extends to estimating systemic treatment response duration in metastatic castration-resistant prostate cancer (mCRPC) patients

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          Abstract

          Background

          We aimed to test whether the prognostic value of 18 F‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) in metastatic castration-resistant prostate cancer (mCRPC) extends to the estimation of systemic treatment response duration.

          Methods

          mCRPC patients submitted to FDG-PET/CT in four Italian centers from 2005 to 2020 were retrospectively enrolled. Clinical and biochemical data at the time of imaging were collected, and SUV max of the hottest lesion, total metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. The correlation between PET- and biochemical-derived parameters with Overall Survival (OS) was analysed. The prediction of treatment response duration was assessed in the subgroup submitted to FDG-PET/CT in the six months preceding Chemotherapy (namely Docetaxel or Cabazitaxel, 24 patients) or Androgen-Receptor Targeted Agents (ARTA, namely Abiraterone or Enzalutamide, 20 patients) administration.

          Results

          We enrolled 114 mCRPC patients followed-up for a median interval lasting 15 months. While at univariate analysis, prostate-specific antigen (PSA), Alkaline Phosphatase (ALP), MTV, and TLG were associated with OS, at the multivariate Cox regression analysis, the sole MTV could independently predict OS ( p < 0.0001). In the subgroup submitted to FDG-PET/CT before the systemic treatment initiation, PSA and TLG could also predict treatment response duration independently ( p < 0.05). Of note, while PSA could not indicate the best treatment choice, lower TLG was associated with higher success rates for ARTA but had no impact on chemotherapy efficacy.

          Conclusions

          FDG-PET/CT’s prognostic value extends to predicting treatment response duration in mCRPC, thus potentially guiding the systemic treatment selection.

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          FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0

          Ronald Boellaard, Roberto Delgado-Bolton, Wim Oyen … (2014)
          The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.
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            The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

            Jonathan Epstein, Lars Egevad, Mahul B Amin … (2016)
            In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out of 10, it implies that their prognosis is intermediate and contributes to their fear of having a more aggressive cancer. Also, in the literature and for therapeutic purposes, various scores have been incorrectly grouped together with the assumption that they have a similar prognosis. For example, many classification systems consider Gleason score 7 as a single score without distinguishing 3+4 versus 4+3, despite studies showing significantly worse prognosis for the latter. The basis for a new grading system was proposed in 2013 by one of the authors (J.I.E.) based on data from Johns Hopkins Hospital resulting in 5 prognostically distinct Grade Groups. This new system was validated in a multi-institutional study of over 20,000 radical prostatectomy specimens, over 16,000 needle biopsy specimens, and over 5,000 biopsies followed by radiation therapy. There was broad (90%) consensus for the adoption of this new prostate cancer Grading system in the 2014 consensus conference based on: (1) the new classification provided more accurate stratification of tumors than the current system; (2) the classification simplified the number of grading categories from Gleason scores 2 to 10, with even more permutations based on different pattern combinations, to Grade Groups 1 to 5; (3) the lowest grade is 1 not 6 as in Gleason, with the potential to reduce overtreatment of indolent cancer; and (4) the current modified Gleason grading, which forms the basis for the new grade groups, bears little resemblance to the original Gleason system. The new grades would, for the foreseeable future, be used in conjunction with the Gleason system [ie. Gleason score 3+3=6 (Grade Group 1)]. The new grading system and the terminology Grade Groups 1-5 have also been accepted by the World Health Organization for the 2016 edition of Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs.
            Article 0 comments Cited 640 times – based on 0 reviews     Review now
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              AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer.

              Emmanuel Antonarakis, Changxue Lu, Hao Wang … (2014)
              The androgen-receptor isoform encoded by splice variant 7 lacks the ligand-binding domain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of androgen-receptor splice variant 7 messenger RNA (AR-V7) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone. We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospectively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status (positive vs. negative) and prostate-specific antigen (PSA) response rates (the primary end point), freedom from PSA progression (PSA progression-free survival), clinical or radiographic progression-free survival, and overall survival. A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled, of whom 39% and 19%, respectively, had detectable AR-V7 in circulating tumor cells. Among men receiving enzalutamide, AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients (0% vs. 53%, P=0.004) and shorter PSA progression-free survival (median, 1.4 months vs. 6.0 months; P<0.001), clinical or radiographic progression-free survival (median, 2.1 months vs. 6.1 months; P<0.001), and overall survival (median, 5.5 months vs. not reached; P=0.002). Similarly, among men receiving abiraterone, AR-V7-positive patients had lower PSA response rates than AR-V7-negative patients (0% vs. 68%, P=0.004) and shorter PSA progression-free survival (median, 1.3 months vs. not reached; P<0.001), clinical or radiographic progression-free survival (median, 2.3 months vs. not reached; P<0.001), and overall survival (median, 10.6 months vs. not reached, P=0.006). The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for expression of full-length androgen receptor messenger RNA. Detection of AR-V7 in circulating tumor cells from patients with castration-resistant prostate cancer may be associated with resistance to enzalutamide and abiraterone. These findings require large-scale prospective validation. (Funded by the Prostate Cancer Foundation and others.).
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                Author and article information

                Contributors
                Matteo Bauckneht:
                ORCID: http://orcid.org/0000-0002-1937-9116
                matteo.bauckneht@hsanmartino.it
                Journal
                Journal ID (nlm-ta): Prostate Cancer Prostatic Dis
                Journal ID (iso-abbrev): Prostate Cancer Prostatic Dis
                Title: Prostate Cancer and Prostatic Diseases
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 1365-7852
                ISSN (Electronic): 1476-5608
                Publication date (Electronic): 19 May 2021
                Publication date PMC-release: 19 May 2021
                Publication date (Print): 2021
                Volume: 24
                Issue: 4
                Pages: 1198-1207
                Affiliations
                [1 ]GRID grid.410345.7, ISNI 0000 0004 1756 7871, Nuclear Medicine, , IRCCS Ospedale Policlinico San Martino, ; Genova, Italy
                [2 ]GRID grid.5606.5, ISNI 0000 0001 2151 3065, Department of Health Sciences (DISSAL), , University of Genova, ; Genova, Italy
                [3 ]GRID grid.412725.7, Nuclear Medicine, , Spedali Civili of Brescia and University of Brescia, ; Brescia, Italy
                [4 ]Nuclear Medicine, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
                [5 ]GRID grid.7548.e, ISNI 0000000121697570, PhD Program in Clinical and Experimental Medicine, , University of Modena and Reggio Emilia, ; Reggio Emilia, Italy
                [6 ]GRID grid.10438.3e, ISNI 0000 0001 2178 8421, Nuclear Medicine, Department of Biomedical and Dental Sciences and of Morpho-functional Imaging, , University of Messina, ; Messina, Italy
                [7 ]GRID grid.410345.7, ISNI 0000 0004 1756 7871, Medical Oncology Unit 1, , IRCCS Ospedale Policlinico San Martino, ; Genova, Italy
                [8 ]GRID grid.7637.5, ISNI 0000000417571846, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology Unit, , Università degli Studi di Brescia, ASST Spedali Civili, ; Brescia, Italy
                Author information
                http://orcid.org/0000-0002-1937-9116
                Article
                Publisher ID: 391
                DOI: 10.1038/s41391-021-00391-8
                PMC ID: 8616756
                PubMed ID: 34012060
                SO-VID: fb904ecb-46b5-4dd1-b4e0-b2313092c3e1
                Copyright © © The Author(s) 2021
                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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 21 February 2021
                Date revision received : 16 April 2021
                Date accepted : 30 April 2021
                Funding
                Funded by: Italian Ministry of Health - 5x1000 funds 2016
                Funded by: FundRef https://doi.org/10.13039/100007388, Compagnia di San Paolo (Fondazione Compagnia di San Paolo);
                Award ID: 2015.AAI4110.U4917
                Award Recipient :
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s), under exclusive licence to Springer Nature Limited 2021

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prognostic markers,predictive markers,cancer therapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: prognostic markers, predictive markers, cancer therapy

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