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Comparison of 68 Ga-PSMA ligand PET/CT versus conventional cross-sectional imaging for target volume delineation for metastasis-directed radiotherapy for metachronous lymph node metastases from prostate cancer

  • Daniel Walacides
  • Astrid Meier
  • Anne Caroline Knöchelmann
  • Daniele Meinecke
  • Thorsten Derlin
  • Frank M. Bengel
  • Tobias L. Ross
  • Hans-Jürgen Wester
  • Katja Derlin
  • Markus A. Kuczyk
  • Christoph A. J. von Klot
  • Hans Christiansen
  • Christoph HenkenberensEmail author
Original Article

Abstract

Purpose

To assess the differences in the target volume (TV) delineation of metachronous lymph node metastases between 68 Ga-PSMA ligand PET/CT and conventional imaging in a comparative retrospective contouring study.

Patients and methods

Twenty-five patients with biochemical prostate cancer recurrence after primary prostatectomy underwent 68 Ga-PSMA ligand PET/CT in addition to conventional imaging techniques such as CT and/or MR imaging for restaging. All patients were diagnosed with at least one lymph node metastasis. TVs were manually delineated in two different ways: (a) based on conventional imaging (CT/MRI) and (b) based on conventional imaging (CT/MRI) plus 68 Ga-PSMA ligand PET/CT. The size of TVs, overlap rates, and subjective assessment of the difficulty of TV delineation reported by the radiation oncologist (easy/moderate/difficult) were compared.

Results

With the additional information from PSMA ligand PET, 47 lymph node metastases were identified and included in the gross tumor volume (GTV). The median clinical target volume (CTV) of non-PET-based TV delineation was statistically larger than the CTV based on PET imaging (134.8 ml [range 6.9–565.2] versus 44.9 ml [range 4.9–481.3; p = 0.001]). The CTV based on CT/MRI enclosed only 81.3% (39/48) of PET-positive lymph nodes. The CT/MRI-based CTV did not enclose all PET-positive lymph nodes in 24% (6/25) of patients. In 12% (3/25) of patients, all PET-positive lymph nodes were outside of the CT/MRI-based CTV. The median overlap rates (TVPET/TVCT/MRI × 100) were 45.7% (range 0–96.9) for the GTV and 71.7% (range 9.8–98.2) for the CTV. The assessment of difficulty of contouring revealed that contouring with the additional imaging information of the PET was categorized as easy/moderate in 92% (23/25) and as difficult in 8% (2/25) of the cases, whereas contouring based on CT/MRI without PET was categorized as difficult in 56% (14/25) and as easy/moderate in 44% of the cases (11/25; p = 0.003).

Conclusion

68 Ga-PSMA ligand PET/CT is superior to conventional cross-sectional imaging for the delineation of lymph node metastases from prostate cancer. PET-based TV delineation allows for smaller target volumes and should be considered the standard for irradiation of metachronous lymph node metastases in recurrent prostate cancer. Conventional imaging is not sufficiently sensitive for radio-oncological treatment concepts in oligometastatic prostate cancer.

Keywords

PSMA PET Prostate cancer Contouring Lymph node metastases Oligometastases 

Vergleich von 68 Ga-PSMA-Liganden-PET/CT und konventioneller Schnittbildgebung zur Zielvolumendefinition für die metastasengerichtete Strahlentherapie bei metachronen Lymphknotenmetastasen durch Prostatakrebs

Zusammenfassung

Ziel

Die Untersuchung von Unterschieden bei Zielvolumina (ZV) für metachrone Lymphknotenmetastasen zwischen 68 Ga-PSMA-Liganden-PET/CT und konventioneller Bildgebung in einer vergleichenden retrospektiven Konturierungsstudie.

Patienten und Methoden

Fünfundzwanzig Patienten mit biochemischem Rezidiv nach primärer Prostatektomie erhielten zusätzlich zur konventionellen Bildgebung (Computertomographie [CT] und/oder Magnetresonanstomographie [MRT]) ein 68 Ga-PSMA-Liganden-PET/CT zum Re-Staging. Bei allen Patienten wurde mindestens eine Lymphknotenmetastasierung diagnostiziert. Die ZVs wurden auf zwei Wegen konturiert: (a) basierend auf konventioneller Bildgebung (CT/MRT) und (b) basierend auf konventioneller Bildgebung plus 68 Ga-PSMA-Liganden-PET/CT. Die Größe der ZVs, die Überlappungsrate und die subjektive Einschätzung des Schwierigkeitsgrads durch die Strahlentherapeuten (leicht/moderat/schwer) wurden miteinander verglichen.

Ergebnisse

Durch die zusätzliche bildgebende Information der PSMA-Liganden-PET wurden alle 47 Lymphknotenmetastasen korrekt als maligne identifiziert und in das „gross tumor volume“ (GTV) einbezogen. Das klinische Zielvolumen (CTV) des nicht-PET-basierten Konturierens war signifikant größer als das CTV auf PET-Basis (134,8 ml [Spanne 6,9–565,2 ml] versus 44,9 ml [Spanne 4,9–481,3 ml]; p = 0,001). Das CTV auf Basis von CT/MRT umschloss 80,9% (38/47) der PSMA-positiven Lymphknoten. Bei 24% der Patienten (6/25) waren nicht alle der PSMA-PET-positiven Lymphknotenmetastasen vom CTV umschlossen und bei 12% (3/25) lagen alle Lymphknotenmetastasen außerhalb des CTV. Die mediane Überlappungsrate (ZVPET/ZVCT/MRT × 100) betrug 45,7% (Spanne 0–96,9%) für das GTV bzw. 71,7% (Spanne 9,8–98,2%) für das CTV. Bezüglich der Einschätzung des Schwierigkeitsgrads wurde das Konturieren mit zusätzlicher PET-Information in 92% (23/25) als leicht bis moderat und in 8% (2/25) als schwierig kategorisiert, wohingegen dies ohne PET nur auf Basis von CT/MRT in 56% (14/25) als schwer und in 44% (11/25; p = 0,003) als leicht bis moderat eingeschätzt wurde.

Schlussfolgerung

Das 68 Ga-PSMA-Liganden-PET/CT ist der konventionellen Schnittbildgebung zur Konturierung von morphologisch vergrößerten Lymphknotenmetastasen überlegen. Das PET-basierte Konturieren erlaubt zudem kleinere ZV und sollte daher als Standard für die Bestrahlungsplanung von metachronen Lymphknotenmetastasen des rezidivierten Prostatakarzinoms gelten. Konventionelle Bildgebung ist für radioonkologische Behandlungskonzepte bei oligometastasiertem Prostatakarzinom nicht ausreichend sensibel.

Schlüsselwörter

PSMA-PET Prostatakarzinom Konturierung Lymphknotenmetastasen Oligometastasierung 

Notes

Acknowledgements

We thank Bernhard Vaske for his statistical support and review of the statistical results.

Compliance with ethical guidelines

Conflict of interest

D. Walacides is a shareholder of Scintomics. A. Meier, A.C. Knöchelmann, D. Meinecke, T. Derlin,F.M. Bengel, T.L. Ross, H.-J. Wester, K. Derlin, M.A. Kuczyk,C.A.J. von Klot, H. Christiansen, and C. Henkenberens declare that they have no competing interests.

Ethical standards

All patients provided written informed consent prior to 68 Ga-PSMA ligand PET/CT, CT, or MRI. This retrospective study complied with the regulations of the local institutional review board and principles of the Declaration of Helsinki.

References

  1. 1.
    Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics. Ca Cancer J Clin 65:87–108CrossRefGoogle Scholar
  2. 2.
    Han M, Partin AW, Zahurak M et al (2003) Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 169:517–523CrossRefGoogle Scholar
  3. 3.
    Pund CR, Partin AW, Epstein JI et al (1997) Prostate-specific antigen after anatomical retropubic prostatectomy. Pattern of recurrence and cancer control. Urol Clin North Am 24:395–406CrossRefGoogle Scholar
  4. 4.
    Ost P, Decaestecker K, Lambert B et al (2014) Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer. Prostate 74:297–305CrossRefGoogle Scholar
  5. 5.
    Ost P, Reynders D, Decaestecker K (2018) Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence. J Clin Oncol 36:446–453CrossRefGoogle Scholar
  6. 6.
    Oderda M, Joniau S, Palazzetti A et al (2018) Is 11C-choline positron emission tomography/computed tomography accurate to detect nodal relapses of prostate cancer after biochemical recurrence? A Multicentric study based on pathologic conformation from salvage Lymphadenectomy. Eur Urol Focus 4:288–293CrossRefGoogle Scholar
  7. 7.
    Afshar-Oromieh A, Holland-Letz T, Giesel FL et al (2017) Diagnostic performance of 68GaPSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging 44:1258–1268CrossRefGoogle Scholar
  8. 8.
    Derlin T, Schmuck S, Juhl C et al (2018) Imaging characteristics and first experience of [68 ga]THP-PSMA, a novel probe for rapid kit-based ga-68 labeling and PET imaging: comparative analysis with [68 ga]PSMA I&T. Mol Imaging Biol.  https://doi.org/10.1007/s11307-018-1160-8 CrossRefPubMedGoogle Scholar
  9. 9.
    Derlin T, Schmuck S, Juhl C et al (2018) PSA-stratified detection rates for [68 ga]THP-PSMA, a novel probe kit-based ga-68 labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer. Eur J Nucl Med Mol Imaging.  https://doi.org/10.1007/s00259-017-3924-9 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Schmuck S, von Klot CA, Henkenberens C et al (2017) Initial experience with volumetric 68 ga-PSMA I&T PET/CT for assessment for whole-body tumor burden as a quantitative imaging biomarker in patients with prostate cancer. J Nucl Med 58:1962–1968CrossRefGoogle Scholar
  11. 11.
    Schmuck S, Nordlohne S, von Klot CA et al (2017) Comparison of standard and delayed imaging to improve the detection rate of [68 Ga]PSMA I&T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer. Eur J Nucl Med Mol Imaging 44:960–968CrossRefGoogle Scholar
  12. 12.
    Henkenberens C, Derlin T, Bengel FM et al (2017) Patterns of relapse as determined by 68 Ga-PSMA ligand PET7CT after radical prostatectomy: importance for tailoring and individualizing treatment. Strahlenther Onkol.  https://doi.org/10.1007/s00066-017-1231-9 ([Epub ahead of print])CrossRefPubMedGoogle Scholar
  13. 13.
    Henkenberens C, von Klot CA, Ross TL et al (2016) 68 Ga-PSMA ligand PET7CT based radiotherapy in locally recurrenct and recurrent oligometastatic prostate cancer: Early efficacy after primary therapy. Strahlenther Onkol 192:431–439CrossRefGoogle Scholar
  14. 14.
    Afshar-Oromieh A, Avtzi E, Giesel FL et al (2015) 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 42(2):197–209CrossRefGoogle Scholar
  15. 15.
    Giesel FL, Fiedler H, Stefanova M et al (2015) PSMA PET/CT with Glu-urea-Lys-(Ahx)-[68 Ga(HBED-CC)] versus 3D CT volumetric lymph node assessment in recurrent prostate cancer. Eur J Nucl Med Mol Imaging 42(12):1794–1800CrossRefGoogle Scholar
  16. 16.
    Rinnab L, Mottaghy FM, Simon J et al (2008) [11 C] Choline PET/CT for targeted salvage lymph node dissection in patients with biochemical recurrence after primary curative therapy for prostate cancer. Preliminary results of a prospective study. Urol Int 81(2):191–197CrossRefGoogle Scholar
  17. 17.
    Perera M, Papa N, Christidis D et al (2016) Sensitivity, specifity 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 70:926–937CrossRefGoogle Scholar
  18. 18.
    Derlin T, Weiberg D, von Klot C et al (2016) 68 Ga-PSMA I&T PET/CT for assessment of prostate cancer: evaluation of image quality after forced diuresis and delayed imaging. Eur Radiol 26:4345–4353CrossRefGoogle Scholar
  19. 19.
    Weineisen M, Schottelius J, Simecek J et al (2015) 68 Ga- and 177LU-labeled PSA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med 56:1169–1176CrossRefGoogle Scholar
  20. 20.
    Martin R, Jüttler S, Müller M, Wester HJ (2014) Cationic eluate pretreatment for automated synthesis of [68 Ga]CPCR4.2. Nucl Med Biol 41:84–89CrossRefGoogle Scholar
  21. 21.
    Hövels AM, Heesakkers RA, Adang EM et al (2008) The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol 64:387–395CrossRefGoogle Scholar
  22. 22.
    Eiber M, Maurer T, Souvatzoglou M et al (2015) Evaluation of hybrid (6)(8)ga-PSMA ligand PET/CT in 248 patients with biochemical recurrence after radical prostatectomy. J Nucl Med 56:668–674CrossRefGoogle Scholar
  23. 23.
    Stephenson AJ, Scardino PT, Kattan MW et al (2007) Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 25:2035–2041CrossRefGoogle Scholar
  24. 24.
    Rauscher I, Maurer T, Beer AJ et al (2016) Value of 68 ga-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 57:1713–1719CrossRefGoogle Scholar
  25. 25.
    van Leeuwen PJ, Emmett L, Ho B et al (2017) Prospective evaluation of 68Gallium-prostate-specific membrane antigen positron emission tomography/computed tomography for preoperative lymph node staging in prostate cancer. BJU Int 119:209–215CrossRefGoogle Scholar
  26. 26.
    Guckenberger M, Baier K, Richter A et al (2008) Does intensity modulated radiation therapy (IMRT) prevent additional toxicity of treating the pelvic lymph nodes compared to treatment of the prostate only? Radiat Oncol.  https://doi.org/10.1186/1748-717X-3-3 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zelefsky MJ, Chan H, Hunt M et al (2006) Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer. J Urol 176:1415–1419CrossRefGoogle Scholar
  28. 28.
    Rischke HC, Schultze-Seemann W, Wieser G et al (2015) Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only. Strahlenther Onkol 4:310–320CrossRefGoogle Scholar
  29. 29.
    Picchio M, Berardi G, Fodor A et al (2014) 11C-choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer. Eur J Nucl Med Mol Imaging 41:1270–1279CrossRefGoogle Scholar
  30. 30.
    Schick U, Jorcano S, Nouet P et al (2013) Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases. Acta Oncol 52:1622–1628CrossRefGoogle Scholar
  31. 31.
    Würschmidt F, Petersen Wahl CA et al (2011) 18F]fluorethylcoline-PET/CT imaging for radiation treatment planning of recurrent and primary prostate cancer with dose escalation to PET/CT-positive lymph nodes. Radiat Oncol 6:44.  https://doi.org/10.1186/1748-717X-6-44 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Zamboglou C, Drendel V, Jilg CA et al (2017) Comparison of 68 Ga-HBED-CC PSMA-PET/CT and multiparametric mRI for grosstumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology. Theranostics 7:228–237CrossRefGoogle Scholar
  33. 33.
    Sanli Y, Kuyumcu S, Sanli O et al (2017) Relationships between serum PSA levels, Gleason scores and results of 68 Ga-PSMAPET/CT in patients with recurrent prostate cancer. Ann Nucl Med 31:709–717CrossRefGoogle Scholar
  34. 34.
    Berliner C, Tienken M, Frenzel T et al (2017) Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [68 Ga]PSMA I&T and comparison with published data of [68 Ga]PSMA HBED-CC. Eur J Nucl Med Mol Imaging 44:670–677CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Daniel Walacides
    • 1
  • Astrid Meier
    • 1
  • Anne Caroline Knöchelmann
    • 1
  • Daniele Meinecke
    • 1
  • Thorsten Derlin
    • 3
  • Frank M. Bengel
    • 3
  • Tobias L. Ross
    • 3
  • Hans-Jürgen Wester
    • 4
  • Katja Derlin
    • 5
  • Markus A. Kuczyk
    • 2
  • Christoph A. J. von Klot
    • 2
  • Hans Christiansen
    • 1
  • Christoph Henkenberens
    • 1
    Email author return OK on get
  1. 1.Department of Radiation OncologyHannover Medical SchoolHannoverGermany
  2. 2.Department of Urology and Urologic OncologyHannover Medical SchoolHannoverGermany
  3. 3.Department of Nuclear MedicineHannover Medical SchoolHannoverGermany
  4. 4.Pharmaceutical RadiochemistryTechnical University MunichGarchingGermany
  5. 5.Department of RadiologyHannover Medical SchoolHannoverGermany

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