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Performance of [68Ga] Ga-PSMA 11 PET for detecting prostate cancer in the lymph nodes before salvage lymph node dissection: a systematic review and meta-analysis

Prostate Cancer and Prostatic Diseases volume 23, pages 1–10 (2020)Cite this article

Subjects

Abstract

Background

Salvage lymph node dissection (sLND) for nodal recurrence in prostate cancer (PCa) patients with biochemical recurrence (BCR) is still not recommended in current guidelines, because of the diagnostic inaccuracy of current conventional imaging. To assess the performance of [68Ga] Ga-prostate-specific membrane antigen conjugate 11 positron emission tomography (PSMA-PET) in detecting PCa lymph node metastasis using pathologic confirmation through sLND.

Methods

Literature search was conducted using the MEDLINE, SCOPUS, Web of Science, and Cochrane Library on November 11th, 2018 to identify the eligible studies. Studies were eligible if they investigated the diagnostic performance of PSMA-PET before sLND in PCa patients with BCR and reported the number of true positive, false positive, false negative, and true negative on a lesion-based and/or field-based analyses to compare with histopathologic findings in sLND specimens.

Results

Fourteen studies published between 2015 and 2018 comprising 462 patients were selected in this systematic review and meta-analysis. The positive predictive value of PSMA-PET before sLND on a patient-based analysis ranged between 0.70 and 0.93. The pooled sensitivity using lesion-based and field-based analyses were 0.84 (95%CI: 0.61–0.95) and 0.82 (95%CI: 0.72–0.89), respectively. The pooled specificity using lesion-based and field-based analyses were 0.97 (95%CI: 0.95–0.99) and 0.95 (95%CI: 0.70–0.99), respectively. The diagnostic odds ratio using lesion-based and field-based analyses were 189 (95%CI: 39–920) and 82 (95%CI: 8–832), respectively.

Conclusions

PSMA-PET before sLND provided highly accurate performance with clinically relevant high positive and negative predictive values for detecting lymph node disease in patients with BCR after local treatment with curative intent for PCa. PSMA-PET can identify the patients who are likely to benefit from sLND and possibly direct to lesion or region-based dissection.

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References

  1. Eggener SE, Scardino PT, Walsh PC, Han M, Partin AW, Trock BJ, et al. Predicting 15-year prostate cancer specific mortality after radical prostatectomy. J Urol. 2011;185:869–75.

    Article  Google Scholar 

  2. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol. 2017;71:618–29.

    Article  Google Scholar 

  3. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. J Am Med Assoc. 2005;294:433–9.

    Article  CAS  Google Scholar 

  4. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71:630–42.

    Article  Google Scholar 

  5. Nini A, Gandaglia G, Fossati N, Suardi N, Cucchiara V, Dell’Oglio P, et al. Patterns of clinical recurrence of node-positive prostate cancer and impact on long-term survival. Eur Urol. 2015;68:777–84.

    Article  Google Scholar 

  6. Heidenreich A, Moul JW, Shariat S, Karnes RJ. Role of salvage lymph node dissection in prostate cancer. Curr Opin Urol. 2016;26:581–9.

    Article  Google Scholar 

  7. 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. 2019. pii: S0302–2838(19)30095–8. https://doi.org/10.1016/j.eururo.2019.01.049. [Epub ahead of print].

  8. Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, specificity, and predictors of positive (68)Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70:926–37.

    Article  Google Scholar 

  9. 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 68Ga-PSMA-HBED-CC than with 18F-fluoroethylcholine PET/CT. Eur J Nucl Med Mol Imaging. 2016;43:1410–7.

    Article  Google Scholar 

  10. Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58:982–90.

    Article  Google Scholar 

  11. Arends LR, Hamza TH, van Houwelingen JC, Heijenbrok-Kal MH, Hunink MG, Stijnen T. Bivariate random effects meta-analysis of ROC curves. Med Decis Mak. 2008;28:621–38.

    Article  CAS  Google Scholar 

  12. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  Google Scholar 

  13. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155:529–36.

    Article  Google Scholar 

  14. Hijazi S, Meller B, Leitsmann C, Strauss A, Meller J, Ritter CO, et al. Pelvic lymph node dissection for nodal oligometastatic prostate cancer detected by 68Ga-PSMA-positron emission tomography/computerized tomography. Prostate. 2015;75:1934–40.

    Article  CAS  Google Scholar 

  15. Herlemann A, Wenter V, Kretschmer A, Thierfelder KM, Bartenstein P, Faber C, et al. 68Ga-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;70:553–7.

    Article  CAS  Google Scholar 

  16. Rauscher I, Maurer T, Beer A, Haller B, Gschwend J, Schwaiger M, et al. Value of 68Ga-PSMA HBED-CC PET for the assessment of lymph node metastases in prostate cancer patients with biochemical recurrence: retrospective comparison with histopathology after salvage lymphadenectomy. J Nucl Med. 2016;57:1713–9.

  17. Sahlmann CO, Meller B, Bouter C, Ritter CO, Strobel P, Lotz J, et al. Biphasic (6)(8)Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma. Eur J Nucl Med Mol Imaging. 2016;43:898–905.

    Article  CAS  Google Scholar 

  18. Fossati N, Suardi N, Gandaglia G, Stabile A, Colicchia M, Karnes RJ, et al. MP77-01 11C-choline versus 68GA-PSMA PET/CT scan for the detection of nodal recurrence from prostate cancer: results from a large, multi-institutional salvage lymph node dissection series. J Urol. 2017;197:e1021.

    Google Scholar 

  19. Herlemann A, Kretschmer A, Buchner A, Karl A, Tritschler S, El-Malazi L, et al. Salvage lymph node dissection after68Ga-PSMA or18F-FEC PET/CT for nodal recurrence in prostate cancer patients. Oncotarget. 2017;8:84180–92.

    Article  Google Scholar 

  20. Jilg CA, Drendel V, Rischke C, 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;7:1770–80.

    Article  CAS  Google Scholar 

  21. Siriwardana A, Thompson J, van Leeuwen PJ, Doig S, Kalsbeek A, Emmett L, et al. Initial multicentre experience of68gallium-PSMA PET/CT guided robot-assisted salvage lymphadenectomy: acceptable safety profile but oncological benefit appears limited. BJU Int. 2017;120:673–81.

    Article  CAS  Google Scholar 

  22. Dundee P, Gross T, Moran D, Ryan A, Ballok Z, Peters J, et al. Ga-labeled prostate-specific membrane antigen ligand-positron-emission tomography: still just the tip of the iceberg. Urology. 2018;120:187–91.

    Article  Google Scholar 

  23. Linxweiler J, Saar M, Al-Kailani Z, Janssen M, Ezziddin S, Stockle M, et al. Robotic salvage lymph node dissection for nodal-only recurrences after radical prostatectomy: perioperative and early oncological outcomes. Surg Oncol. 2018;27:138–45.

    Article  Google Scholar 

  24. 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. 2018. pii: S2405–4569(18)30191–3. https://doi.org/10.1016/j.euf.2018.07.025. [Epub ahead of print].

  25. Pfister D, Kohl T, Porres-Knoblauch D, Haidl F, Heidenreich A. 68-Ga-PSMA-PET in lymph node staging in PSA recurrent prostate cancer-does the primary influence the result? J Clin Oncol. 2018;36(6_suppl):210–210.

    Article  Google Scholar 

  26. Savio L, Mota FHA, Santos R, da Cruz JA, Passerotti C. Salvage robot-assisted retroperitoneal lymphadenectomy for prostate cancer nodal recurrence only detected by 68GA-PSMA PET CT: technical aspects and results? J Urol. 2018;199:E821–E821.

    Article  Google Scholar 

  27. Evangelista L, Zattoni F, Karnes RJ, Novara G, Lowe V. Radiolabeled choline PET/CT before salvage lymphadenectomy dissection: a systematic review and meta-analysis. Nucl Med Commun. 2016;37:1223–31.

    Article  CAS  Google Scholar 

  28. Afshar-Oromieh A, Avtzi E, Giesel FL, Holland-Letz T, Linhart HG, Eder M, et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2015;42:197–209.

    Article  CAS  Google Scholar 

  29. Yaxley JW, Raveenthiran S, Nouhaud FX, Samartunga H, Yaxley AJ, Coughlin G, et al. Outcomes of primary lymph node staging of intermediate and high risk prostate cancer with 68Ga-PSMA positron emission tomography/computerized tomography compared to histological correlation of pelvic lymph node pathology: can preoperative 68Ga-PSMA positron emission tomography/computerized tomography replace pelvic lymph node dissection for prostate cancer staging? J Urol. 2019;201:815–20.

  30. Chade DC, Eastham J, Graefen M, Hu JC, Karnes RJ, Klotz L, et al. Cancer control and functional outcomes of salvage radical prostatectomy for radiation-recurrent prostate cancer: a systematic review of the literature. Eur Urol. 2012;61:961–71.

    Article  Google Scholar 

  31. Maurer T, Weirich G, Schottelius M, Weineisen M, Frisch B, Okur A, et al. Prostate-specific membrane antigen-radioguided surgery for metastatic lymph nodes in prostate cancer. Eur Urol. 2015;68:530–4.

    Article  Google Scholar 

  32. Rauscher I, Düwel C, Wirtz M, Schottelius M, Wester HJ, Schwamborn K, et al. Value of111In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up. BJU Int. 2017;120:40–47.

    Article  CAS  Google Scholar 

  33. Hofman MS, Murphy DG, Williams SG, Nzenza T, Herschtal A, Lourenco RA, et al. A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol. BJU Int. 2018;122:783–93.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Medical University of Vienna, Vienna, Austria

    Shoji Kimura, Mohammad Abufaraj, Florian Janisch, Takehiro Iwata, Mehdi Kardoust Parizi, Beat Foerster & Shahrokh F. Shariat

  2. Department of Urology, Jikei University School of Medicine, Tokyo, Japan

    Shoji Kimura & Shin Egawa

  3. Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan

    Mohammad Abufaraj

  4. Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Florian Janisch

  5. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Takehiro Iwata

  6. Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Kardoust Parizi

  7. Department of Urology, Kantonsspital Winterthur, Winterthur, Switzerland

    Beat Foerster

  8. Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

    Nicola Fossati & Alberto Briganti

  9. Vita-Salute San Raffaele University, Milan, Italy

    Nicola Fossati & Alberto Briganti

  10. Department of Biomedical Imaging and Image Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria

    Markus Hartenbach

  11. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia

    Shahrokh F. Shariat

  12. Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Shahrokh F. Shariat

  13. Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Shahrokh F. Shariat

  14. Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria

    Shahrokh F. Shariat

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Contributions

Project development: SK, AB, SE, MH, and SFS. Data collection: SK, MA, FJ, TI, MK, BF, and NF. Data analysis: SK, MA, FJ, TI, MK, and BF. Manuscript writing/editing: SK, MA, FJ, TI, MK, BF, NF, AB, SE, MH, and SFS.

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Correspondence to Shahrokh F. Shariat.

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Kimura, S., Abufaraj, M., Janisch, F. et al. Performance of [68Ga] Ga-PSMA 11 PET for detecting prostate cancer in the lymph nodes before salvage lymph node dissection: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 23, 1–10 (2020). https://doi.org/10.1038/s41391-019-0156-z

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