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•• Fossati N, Suardi N, Gandaglia G, Bravi CA, Soligo M, Karnes RJ, et al. Identifying the optimal candidate for salvage lymph node dissection for nodal recurrence of prostate cancer: results from a large, multi-institutional analysis. Eur Urol. 2019;75(1):176–83. https://doi.org/10.1016/j.eururo.2018.09.009The study aimed to identify optimal candidates for SLND based on predictive preoperative characteristics. In total, 654 patients were treated with pSLND for nodal recurrence of PCa documented by either PET/CT using 11C-choline or 68-Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) ligand.
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Montorsi F, Gandaglia G, Fossati N, Suardi N, Pultrone C, De Groote R, et al. Robot-assisted salvage lymph node dissection for clinically recurrent prostate cancer. Eur Urol. 2017;72(3):432–8. https://doi.org/10.1016/j.eururo.2016.08.051.
•• Mazzone E, Preisser F, Nazzani S, Tian Z, Bandini M, Gandaglia G, et al. The effect of lymph node dissection in metastatic prostate cancer patients treated with radical prostatectomy: a contemporary analysis of survival and early postoperative outcomes. Eur Urol Oncol. 2019;2(5):541–8. https://doi.org/10.1016/j.euo.2018.10.010The study compared 330 patients with newly diagnosed metastatic prostate cancer treated with prostatectomy between 2004 and 2014; 199 underwent LND and 131 did not. The study showed lower cancer-specific mortality and overall mortality in patients with LND at RP (52% and 35%, respectively) relative to no LND.
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Karnes RJ, Murphy CR, Bergstralh EJ, DiMonte G, Cheville JC, Lowe VJ, et al. Salvage lymph node dissection for prostate cancer nodal recurrence detected by 11C-choline positron emission tomography/computerized tomography. J Urol. 2015;193(1):111–6. https://doi.org/10.1016/j.juro.2014.08.082.
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•• Trabulsi EJ, Rumble RB, Jadvar H, Hope T, Pomper M, Turkbey B, et al. Optimum imaging strategies for advanced prostate cancer: ASCO guideline. J Clin Oncol. 2020:JCO1902757. https://doi.org/10.1200/JCO.19.02757The most recent 2020 ASCO Guideline that reports various recommendations for when next-generational imaging can be utilized to identify advanced prostate cancer.
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Chang CH, Wu HC, Tsai JJ, Shen YY, Changlai SP, Kao A. Detecting metastatic pelvic lymph nodes by 18F-2-deoxyglucose positron emission tomography in patients with prostate-specific antigen relapse after treatment for localized prostate cancer. Urol Int. 2003;70(4):311–5. https://doi.org/10.1159/000070141.
Picchio M, Messa C, Landoni C, Gianolli L, Sironi S, Brioschi M, et al. Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol. 2003;169(4):1337–40. https://doi.org/10.1097/01.ju.0000056901.95996.43.
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Bhargava P, Ravizzini G, Chapin BF, Kundra V. Imaging biochemical recurrence after prostatectomy: where are we headed? AJR Am J Roentgenol. 2020;214:1–11. https://doi.org/10.2214/AJR.19.21905.
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Daouacher G, von Below C, Gestblom C, Ahlstrom H, Grzegorek R, Wassberg C, et al. Laparoscopic extended pelvic lymph node (LN) dissection as validation of the performance of [(11) C]-acetate positron emission tomography/computer tomography in the detection of LN metastasis in intermediate- and high-risk prostate cancer. BJU Int. 2016;118(1):77–83. https://doi.org/10.1111/bju.13202.
Schumacher MC, Radecka E, Hellstrom M, Jacobsson H, Sundin A. [11C]Acetate positron emission tomography-computed tomography imaging of prostate cancer lymph-node metastases correlated with histopathological findings after extended lymphadenectomy. Scand J Urol. 2015;49(1):35–42. https://doi.org/10.3109/21681805.2014.932840.
Fricke E, Machtens S, Hofmann M, van den Hoff J, Bergh S, Brunkhorst T, et al. Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients. Eur J Nucl Med Mol Imaging. 2003;30(4):607–11. https://doi.org/10.1007/s00259-002-1104-y.
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Rajarubendra N, Almeida F, Manojlovic Z, Ohe C, Ahmadi N, Cacciamani G, et al. Histological validation of 11carbon-acetate positron emission tomography/computerized tomography in detecting lymph node metastases in prostate cancer. J Urol. 2019;201(2):332–41. https://doi.org/10.1016/j.juro.2018.09.028.
Regula N, Haggman M, Johansson S, Sorensen J. Malignant lipogenesis defined by (11)C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy. Eur J Nucl Med Mol Imaging. 2016;43(12):2131–8. https://doi.org/10.1007/s00259-016-3449-7.
Yu EY, Muzi M, Hackenbracht JA, Rezvani BB, Link JM, Montgomery RB, et al. C11-acetate and F-18 FDG PET for men with prostate cancer bone metastases: relative findings and response to therapy. Clin Nucl Med. 2011;36(3):192–8. https://doi.org/10.1097/RLU.0b013e318208f140.
• Regula N, Kostaras V, Johansson S, Trampal C, Lindstrom E, Lubberink M, et al. Comparison of (68)Ga-PSMA-11 PET/CT with (11)C-acetate PET/CT in re-staging of prostate cancer relapse. Sci Rep. 2020a;10(1):4993. https://doi.org/10.1038/s41598-020-61910-6This prospective comparative study indicates 68Ga-PSMA-11 PET/CT had better diagnostic performance than 11C-acetate PET/CT in detecting lymph node (81% vs. 60%, p = 0.02) and bone metastasis (95% vs. 61%, p = 0.0001) in patients with PCa recurrence. However, studies have shown PSMA expression is heterogeneous which may indicate pairing an additional tracer.
• Regula N, Honarvar H, Lubberink M, Jorulf H, Ladjevardi S, Haggman M, et al. Carbon flux as a measure of prostate cancer aggressiveness: [(11)C]-acetate PET/CT. Int J Med Sci. 2020b;17(2):214–23. https://doi.org/10.7150/ijms.39542Prospective study that included 21 patients (mean age 65, range 51–75 years) with newly diagnosed low–moderate-risk prostate cancer received MRI and dynamic 11C-acetate PET-CT examinations of the pelvis, then in vitro kinetics studies of 11C-acetate were conducted. The study demonstrated potential for dynamic 11C-acetate-PET to visualize and estimate prostate cancer aggressiveness.
• Akin-Akintayo OO, Jani AB, Odewole O, Tade FI, Nieh PT, Master VA, et al. Change in salvage radiotherapy management based on guidance with FACBC (fluciclovine) PET/CT in postprostatectomy recurrent prostate cancer. Clin Nucl Med. 2017;42(1):e22–e8. https://doi.org/10.1097/RLU.0000000000001379In a prospective randomized trial of 42 post-prostatectomy patients who obtained fluciclovine PET-CT, 34 (81.0%) received positive results of PCa recurrence. All 42 study participants were initially planned for radiotherapy but overall radiotherapy decisions changed in 17 (40.85%) of the 42 patients. Also, fluciclovine PET-CT was shown to perform better than similar studies utilizing 11C-choline PET-CT.
Bach-Gansmo T, Nanni C, Nieh PT, Zanoni L, Bogsrud TV, Sletten H, et al. Multisite experience of the safety, detection rate and diagnostic performance of fluciclovine ((18)F) positron emission tomography/computerized tomography imaging in the staging of biochemically recurrent prostate cancer. J Urol. 2017;197(3 Pt 1):676–83. https://doi.org/10.1016/j.juro.2016.09.117.
Nanni C, Zanoni L, Pultrone C, Schiavina R, Brunocilla E, Lodi F, et al. (18)F-FACBC (anti1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid) versus (11)C-choline PET/CT in prostate cancer relapse: results of a prospective trial. Eur J Nucl Med Mol Imaging. 2016;43(9):1601–10. https://doi.org/10.1007/s00259-016-3329-1.
Odewole OA, Tade FI, Nieh PT, Savir-Baruch B, Jani AB, Master VA, et al. Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT. Eur J Nucl Med Mol Imaging. 2016;43(10):1773–83. https://doi.org/10.1007/s00259-016-3383-8.
•• Savir-Baruch B, Lovrec P, Solanki AA, Adams WH, Yonover PM, Gupta G, et al. Fluorine-18-labeled fluciclovine PET/CT in clinical practice: factors affecting the rate of detection of recurrent prostate cancer. AJR Am J Roentgenol. 2019;213(4):851–8. https://doi.org/10.2214/AJR.19.21153A retrospective study of 152 patients with recurrent PCa after primary treatment reported high fluciclovine PET/CT positivity rate of prostate and extraprostatic recurrence correlated with increased PSA levels.
Selnaes KM, Kruger-Stokke B, Elschot M, Willoch F, Storkersen O, Sandsmark E, et al. (18)F-Fluciclovine PET/MRI for preoperative lymph node staging in high-risk prostate cancer patients. Eur Radiol. 2018;28(8):3151–9. https://doi.org/10.1007/s00330-017-5213-1.
•• Pernthaler B, Kvaternik H, Aigner RM. A prospective head-to-head comparison of 18F-fluciclovine with 68Ga-PSMA-11 in biochemical recurrence of prostate cancer in PET/CT: a special aspect in imaging local recurrence: reply. Clin Nucl Med. 2020. https://doi.org/10.1097/RLU.0000000000002913This prospective study provides a direct comparison between PET-CT tracers 18F-fluciclovine vs. 68Ga-PSMA-11 with BCR. 18F-Fluciclovine PET-CT performed better than 68Ga-PSMA-11 PET-CT in detecting local recurrence (37.9% and 27.6%, respectively, p = 0.03).
Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52(4):637–40. https://doi.org/10.1016/s0090-4295(98)00278-7.
Wright GL Jr, Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1(1):18–28. https://doi.org/10.1016/1078-1439(95)00002-y.
Prasad V, Steffen IG, Diederichs G, Makowski MR, Wust P, Brenner W. Biodistribution of [(68)Ga]PSMA-HBED-CC in patients with prostate cancer: characterization of uptake in normal organs and tumour lesions. Mol Imaging Biol. 2016;18(3):428–36. https://doi.org/10.1007/s11307-016-0945-x.
Walker SM, Lim I, Lindenberg L, Mena E, Choyke PL, Turkbey B. Positron emission tomography (PET) radiotracers for prostate cancer imaging. Abdom Radiol (NY). 2020;45:2165–75. https://doi.org/10.1007/s00261-020-02427-4.
De Visschere PJL, Standaert C, Futterer JJ, Villeirs GM, Panebianco V, Walz J, et al. A systematic review on the role of imaging in early recurrent prostate cancer. Eur Urol Oncol. 2019;2(1):47–76. https://doi.org/10.1016/j.euo.2018.09.010.
• Perera M, Papa N, Roberts M, Williams M, Udovicich C, Vela I, et al. Gallium-68 prostate-specific membrane antigen positron emission tomography in advanced prostate cancer-updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: a systematic review and meta-analysis. Eur Urol. 2020;77(4):403–17. https://doi.org/10.1016/j.eururo.2019.01.049In a meta-analysis of 37 studies, 68Ga-PSMA PET showed evidence of superior sensitivity and specificity compared to alternate techniques, especially with the detection of metastases with biochemical recurrence in patients with low PSA levels.
Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. (68)Ga-PSMA positron emission tomography/computed tomography provides accurate staging of lymph node regions prior to lymph node dissection in patients with prostate cancer. Eur Urol. 2016;70(4):553–7. https://doi.org/10.1016/j.eururo.2015.12.051.
Jilg CA, Drendel V, Rischke HC, Beck T, Vach W, Schaal K, et al. Diagnostic accuracy of Ga-68-HBED-CC-PSMA-ligand-PET/CT before salvage lymph node dissection for recurrent prostate cancer. Theranostics. 2017;7(6):1770–80. https://doi.org/10.7150/thno.18421.
Mandel P, Tilki D, Chun FK, Pristupa E, Graefen M, Klutmann S, et al. Accuracy of (68)Ga-prostate-specific membrane antigen positron emission tomography for the detection of lymph node metastases before salvage lymphadenectomy. Eur Urol Focus. 2020;6(1):71–3. https://doi.org/10.1016/j.euf.2018.07.025.
Pfister D, Porres D, Heidenreich A, Heidegger I, Knuechel R, Steib F, et al. Detection of recurrent prostate cancer lesions before salvage lymphadenectomy is more accurate with (68)Ga-PSMA-HBED-CC than with (18)F-fluoroethylcholine PET/CT. Eur J Nucl Med Mol Imaging. 2016;43(8):1410–7. https://doi.org/10.1007/s00259-016-3366-9.
Rauscher I, Maurer T, Beer AJ, Graner FP, Haller B, Weirich G, et al. Value of 68Ga-PSMA HBED-CC PET for the assessment of lymph node metastases in prostate cancer patients with biochemical recurrence: comparison with histopathology after salvage lymphadenectomy. J Nucl Med. 2016;57(11):1713–9. https://doi.org/10.2967/jnumed.116.173492.
•• Calais J, Ceci F, Eiber M, Hope TA, Hofman MS, Rischpler C, et al. (18)F-Fluciclovine PET-CT and (68)Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. Lancet Oncol. 2019;20(9):1286–94. https://doi.org/10.1016/S1470-2045(19)30415-2This recent prospective study compared 18F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in detecting recurrent PCa post-prostatectomy. Of the 50 patients, 68Ga-PSMA-11 PET-CT had higher detection rates in comparison to 18F-fluciclovine PET-CT (56% vs. 26%, respectively) especially at low PSA levels. The article also reports higher reader agreement with 68Ga-PSMA-11 PET-CT.
Afshar-Oromieh A, Zechmann CM, Malcher A, Eder M, Eisenhut M, Linhart HG, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014a;41(1):11–20. https://doi.org/10.1007/s00259-013-2525-5.
•• Fossati N, Scarcella S, Gandaglia G, Suardi N, Robesti D, Boeri L, et al. Underestimation of PET/CT scan in assessing tumour burden of men with nodal recurrence from prostate cancer: head-to-head comparison of (68)Ga-PSMA and (11)C-choline in a large, multi-institutional series of extended salvage lymph node dissections. J Urol. 2020:101097JU0000000000000800. https://doi.org/10.1097/JU.0000000000000800The large study (n = 641) compared 11C-choline and 68Ga-PSMA PET-CT for patients receiving SLND that have PCa recurrence after primary treatment. The study concludes that in these patients, both PET-CT tracers significantly underestimated tumor burden. Between the two tracers, 68Ga-PSMA PET-CT had a superior detection rate in patients with low PSA levels (≤ 1.5 ng/mL) and lower number of positive spots (≤ 2).
• Schwenck J, Rempp H, Reischl G, Kruck S, Stenzl A, Nikolaou K, et al. Comparison of (68)Ga-labelled PSMA-11 and (11)C-choline in the detection of prostate cancer metastases by PET/CT. Eur J Nucl Med Mol Imaging. 2017;44(1):92–101. https://doi.org/10.1007/s00259-016-3490-6The article reports 68Ga-PSMA-11 PET had a higher detection rate of prostate cancer metastasis to lymph nodes than 11C-choline PET, especially in patients with a PSA level of less than 1 ng/mL. The study did not see a statistically significant difference in detection rates at higher PSA levels.
Luiting HB, van Leeuwen PJ, Busstra MB, Brabander T, van der Poel HG, Donswijk ML, et al. Use of gallium-68 prostate-specific membrane antigen positron-emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature. BJU Int. 2020;125(2):206–14. https://doi.org/10.1111/bju.14944.
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