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Publication Metadata only European association of nuclear medicine focus 5: consensus on molecular imaging and theranostics in prostate cancer(Elsevier B.V., 2024) Oprea-Lager, DE; MacLennan, S; Bjartell, A; Briganti, A; Burger, IA; de Jong, I; De Santis, M; Eberlein, U; Emmett, L; Fizazi, K; Gillessen, S; Herrmann, K; Heskamp, S; Iagaru, A; Jereczek-Fossa, BA; Kunikowska, J; Lam, M; Nanni, C; O'Sullivan, JM; Panebianco, V; Sala, E; Sathekge, M; Sosnowski, R; Tombal, B; Treglia, G; Tunariu, N; Walz, J; Yakar, D; Dierckx, R; Sartor, O; Fanti, S.; Tilki, Derya; School of Medicine; Koç University HospitalBackground: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications. Objective: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa. Design, setting, and participants: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting. Outcome measurements and statistical analysis: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores. Results and limitations: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy. Conclusions: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community. Patient summary: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.Publication Metadata only The “ins and outs” of prostate specific membrane antigen (psma) as specific target in prostate cancer therapy(Springer, 2023) Eltit, Felipe; Robinson, Nicole; Yu, Pak Lok Ivan; Pandey, Mitali; Lozada, Jerome; Guo, Yubin; Sharma, Manju; Ozturan, Dogancan; Ganier, Laetitia; Belanger, Eric; Perrin, David M.; Cox, Michael E.; Goldenberg, S. Larry; Lack, Nathan Alan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of MedicineProstate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate gland and is strongly upregulated in prostatic adenocarcinoma, with elevated expression correlating with metastasis, progression, and androgen independence. Because of its specificity, PSMA is a major target of prostate cancer therapy;however, detectable levels of PSMA are also found in other tissues, especially in salivary glands and kidney, generating bystander damage of these tissues. Antibody target therapy has been used with relative success in reducing tumor growth and prostate specific antigen (PSA) levels. However, since antibodies are highly stable in plasma, they have prolonged time in circulation and accumulate in organs with an affinity for antibodies such as bone marrow. For that reason, a second generation of PSMA targeted therapeutic agents has been developed. Small molecules and minibodies have had promising clinical trial results, but concerns about their specificity had arisen with side effects due to accumulation in salivary glands and kidneys. Herein we study the specificity of small molecules and minibodies that are currently being clinically tested. We observed a high affinity of these molecules for PSMA in prostate, kidney and salivary gland, suggesting that their effect is not prostate specific. The search for specific prostate target agents must continue so as to optimally treat patients with prostate cancer, while minimizing deleterious effects in other PSMA expressing tissues. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.Publication Metadata only The 2019 Genitourinary Pathology Society (GUPS) white paper on contemporary grading of prostate cancer(College of American Pathologists, 2021) Epstein, Jonathan I.; Amin, Mahul B.; Fine, Samson W.; Algaba, Ferran; Aron, Manju; Beltran, Antonio Lopez; Brimo, Fadi; Cheville; John C.; Colecchia, Maurizio; Comperat, Eva; Cunha, Isabela Werneck da; Delprado, Warick; DeMarzo, Angelo M.; Giannico, Giovanna A.; Gordetsky, Jennifer B.; Guo, Charles C.; Hansel, Donna E.; Hirsch, Michelle S.; Humphrey, Jiaoti HuangPeter A.; Jimenez, Rafael E.; Khani, Francesca; Kong, Qingnuan; N. Kryvenko, Oleksandr; Kunju, L. Priya; Lal, Priti; Latour, Mathieu; Lotan, Tamara; Maclean, Fiona; Magi-Galluzzi, Cristina; Mehra, Rohit; Menon, Santosh; Miyamoto, Hiroshi; Montironi, Rodolfo; J. Netto, George; Nguyen, Jane K.; O. Osunkoya, Adeboye; Parwani, Anil; Robinson, Brian D.; Rubin, Mark A.; Shah, Rajal B.; So, Jeffrey S.; Takahashi, Hiroyuki; Tavora, Fabio; Tretiakova, Maria S.; True, Lawrence; Wobker, Sara E.; Yang, Ximing J.; Zhou, Ming; Zynger, Debra L.; Trpkov, Kiril; Baydar, Dilek Ertoy; Faculty Member; School of Medicine; 8025Context.—Controversies and uncertainty persist in prostate cancer grading. Objective.—To update grading recommendations. Data Sources.—Critical review of the literature along with pathology and clinician surveys. Conclusions.—Percent Gleason pattern 4 (%GP4) is as follows: (1) report %GP4 in needle biopsy with Grade Groups (GrGp) 2 and 3, and in needle biopsy on other parts (jars) of lower grade in cases with at least 1 part showing Gleason score (GS) 4 þ 4 ¼ 8; and (2) report %GP4: less than 5% or less than 10% and 10% increments thereafter. Tertiary grade patterns are as follows: (1) replace ‘‘tertiary grade pattern’’ in radical prostatectomy (RP) with ‘‘minor tertiary pattern 5 (TP5),’’ and only use in RP with GrGp 2 or 3 with less than 5% Gleason pattern 5; and (2) minor TP5 is noted along with the GS, with the GrGp based on the GS. Global score and magnetic resonance imaging (MRI)targeted biopsies are as follows: (1) when multiple undesignated cores are taken from a single MRI-targeted lesion, an overall grade for that lesion is given as if all the involved cores were one long core; and (2) if providing a global score, when different scores are found in the standard and the MRI-targeted biopsy, give a single global score (factoring both the systematic standard and the MRI-targeted positive cores). Grade Groups are as follows: (1) Grade Groups (GrGp) is the terminology adopted by major world organizations; and (2) retain GS 3 þ 5 ¼ 8 in GrGp 4. Cribriform carcinoma is as follows: (1) report the presence or absence of cribriform glands in biopsy and RP with Gleason pattern 4 carcinoma. Intraductal carcinoma (IDC-P) is as follows: (1) report IDC-P in biopsy and RP; (2) use criteria based on dense cribriform glands (.50% of the gland is composed of epithelium relative to luminal spaces) and/or solid nests and/or marked pleomorphism/necrosis; (3) it is not necessary to perform basal cell immunostains on biopsy and RP to identify IDC-P if the results would not change the overall (highest) GS/GrGp part per case; (4) do not include IDC-P in determining the final GS/GrGp on biopsy and/or RP; and (5) ‘‘atypical intraductal proliferation (AIP)’’ is preferred for an intraductal proliferation of prostatic secretory cells which shows a greater degree of architectural complexity and/or cytological atypia than typical high-grade prostatic intraepithelial neoplasia, yet falling short of the strict diagnostic threshold for IDC-P. Molecular testing is as follows: (1) Ki67 is not ready for routine clinical use; (2) additional studies of active surveillance cohorts are needed to establish the utility of PTEN in this setting; and (3) dedicated studies of RNA-based assays in active surveillance populations are needed to substantiate the utility of these expensive tests in this setting. Artificial intelligence and novel grading schema are as follows: (1) incorporating reactive stromal grade, percent GP4, minor tertiary GP5, and cribriform/intraductal carcinoma are not ready for adoption in current practice. © 2021 College of American Pathologists. All rights reserved.