Skip to main content
Log in

68Ga-PSMA ligand PET/CT-based radiotherapy in locally recurrent and recurrent oligometastatic prostate cancer

Early efficacy after primary therapy

68Ga-PSMA-PET/CT-basierte Strahlentherapie beim lokal rezidivierten und oligometastasierten Prostatakarzinom

Frühe Effektivität nach Primärtherapie

  • Original Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Purpose

The goal of this work was to evaluate the early efficacy of 68Ga-PSMA ligand PET/CT imaging for radiotherapy of locally recurrent and/or oligometastatic prostate cancer.

Patients and methods

A total of 29 patients with biochemical recurrence received a 68Ga-PSMA ligand PET/CT for restaging of disease, followed by 3D conformal radiotherapy of metastases or intensity-modulated radiation therapy of the prostate bed. Prostate-specific antigen (PSA) levels and imaging procedures served as the reference standard to assess the treatment efficacy.

Results

PET/CT was positive in 96.6% of patients and revealed that 13.8% of patients had locally recurrent disease, 58.6% had isolated lymph node metastases, 20.7% had isolated bone metastases, and 3.4% showed lymph node metastases and a vertebral metastasis. The median follow-up was 8.3 months (range 3.0–17.3 months). The median PSA prior to radiotherapy was 1.47 ng/ml (range 0.52–32.01 ng/ml) and showed a statistically significant decrease to 0.58 ng/ml (range < 0.07 to 6.33 ng/ml, p < 0.001). Two patients (6.8%) developed progressive disease outside the radiation field after 12.0 and 12.7 months, yielding a local control rate of 100% at the median follow-up. No grade III acute toxicity or late toxicity grade II was observed. Only 2 patients (6.8%) reported persisting grade I diarrhoea according to the LENT-SOMA criteria 3 months after radiotherapy. Deterioration of the urinary or faecal continence was not observed.

Conclusion

Preliminary results in the presented cohort suggest that radiotherapy based on 68Ga-PSMA ligand PET/CT yields effective local control and significant treatment response in terms of PSA levels in the absence of clinically important side effects. Furthermore, this approach delayed the necessity of androgen deprivation therapy or systemic therapy.

Zusammenfassung

Ziel

Beurteilt werden sollte die frühe Effektivität einer 68Ga-PSMA-Liganden-PET/CT-gestützten Strahlentherapie beim lokal rezidivierten und/oder oligometastasierten Prostatakarzinom.

Patienten und Methodik

Neunundzwanzig Patienten mit kontinuierlich steigenden PSA-Werten erhielten ein 68Ga-PSMA-Liganden-PET/CT zum Restaging, gefolgt von einer 3‑D-konformalen Strahlentherapie von Metastasen bzw. einer intensitätsmodulierten Strahlentherapie des Prostatabettes. PSA-Werte und Bildgebungsresultate dienten als Referenzstandard zur Beurteilung der frühen Effektivität.

Ergebnisse

Das PSMA-PET/CT zeigte bei 96,6% der Patienten eine pathologische Tracer-Bindung, 13,8% der Patienten hatten ein Lokalrezidiv der Prostataloge, 58,6% isolierte Lymphknotenmetastasen, 20,7% isolierte Knochenmetastasen und 3,4% pelvine Lymphknotenmetastasen sowie eine singuläre Wirbelkörpermetastase. Das mediane Follow-up betrug 8,3 Monate (Spannbreite 3,0–17,3). Der mediane PSA-Wert vor Strahlentherapie war 1,47 ng/ml (0,52–32,01) und ging statistisch signifikant zurück auf 0,58 ng/ml (<0,07–6,33; p < 0,001). Zwei Patienten (6,8%) zeigte nach 12,0 bzw. 12,7 Monaten einen Progress außerhalb des Bestrahlungsbereiches mit paraaortalen Lymphknotenmetastasen, sodass sich eine lokale Kontrollrate von 100% im medianen Follow-up-Zeitraum ergibt. Es wurden weder Akuttoxizitäten Grad III nach CTCAE noch Spättoxizitäten Grad II nach LENT-SOMA beobachtet. Zwei Patienten (6.8%) hatten 3 Monate nach Bestrahlung eine persistierende Diarrhö Grad I nach LENT-SOMA. Darüber hinaus trat bei keinem Patienten eine Verschlechterung der Harn- oder Stuhlkontinenz auf.

Schlussfolgerung

Nach 68Ga-PSMA-Liganden-PET/CT-basierter Strahlentherapie zeigten sich eine effektive lokale Kontrolle und ein signifikantes PSA-Ansprechen, klinisch relevanten Nebenwirkungen gab es nicht. Zudem wurde der Beginn einer antihormonellen bzw. systemischen Behandlung verzögert.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Grosu A‑L, Piert M, Weber MA et al (2005) Positron emission tomography for radiation treatment planning. Strahlenther Onkol 181(8):483–499

    Article  PubMed  Google Scholar 

  2. Wondergem M, Zant FM van der, Poeg T van der et al (2013) A literature review of 18 F-fluoride PET/CT and 18 F-choline or 11 C-cholie PET/CT for detection of bone metastasis in patients with prostate cancer. Nucl Med Commun 34(10):935–945

    Article  CAS  PubMed  Google Scholar 

  3. Umbehr MH, Müntener M, Hany T et al (2013) The role of 11 C-choline and 18 F-fluorocholine positron emission tomography (PET) and PET/CT in prostate cancer: a systematic review and meta-analysis. Eur Urol 64(1):106–117

    Article  PubMed  Google Scholar 

  4. Decaestecker K, Meerleer G, Lambert B et al (2014) Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence. Radiat Oncol 12(9):135. doi:10.1186/1748-717X-9-135

    Article  Google Scholar 

  5. Eyben FE von, Kairemo K (2014) Meta-analysis of 11 C-choline and 18 F-choline PET/CT for management of patients with prostate cancer. Nucl Med Commun 35(3):221–230

    Article  Google Scholar 

  6. Picchio M, Berardi G, Fodor A et al (2014) (11)C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients. Eur J Nucl Med Mol Imaging 41(7):1270–1279

    Google Scholar 

  7. Jackson WC, Johnson SB, Feng FY et al (2015) Salvage radiation therapy improves metastasis-free survival for clinically aggressive and indolent prostate cancer recurrences after radical prostatectomy. Am J Clin Oncol 38(4):367–372

    Article  PubMed  Google Scholar 

  8. Ost P, Decaestecker K, Lambert B et al (2013) Prognostic factors influencing prostate cancer-specific survival in non-castrate patients with metastatic prostate cancer. Prostate 74(3):297–305

    Article  Google Scholar 

  9. Mottet N, Bellmunt J, Bolla M et al (2011) EAU guidelines on prostate cancer part II: treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 59(4):572–583

    Article  PubMed  Google Scholar 

  10. Mease RC, Foss CA, Pomper MG (2013) PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr Top Med Chem 13(8):951–962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chang SS, O’Keefe DS, Bacich DJ et al (1999) Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res 5(10):2674–2681

    CAS  PubMed  Google Scholar 

  12. Afshar-Oromieh A, Zechman CM, Malcher A et al (2014) Comaparison 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 Mol Imaging 41(1):11–20

    Article  CAS  Google Scholar 

  13. Weineisen M, Schottelius M, Simecek J et al (2015) 68 Ga- and 177 Lu-labeled PSMA I&T: optimization of a PSMA-targeted theranostic concept and first proof-of-concept human studies. J Nucl Med 56(8):1169–1176

    Article  CAS  PubMed  Google Scholar 

  14. Martin R, Jüttler S, Müller M et al (2014) Cationic eluate pretreatment for automated synthesis of [68GA] CPCR4.2. Nucl Med Biol 41(1):84–89

    Article  CAS  PubMed  Google Scholar 

  15. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 16 Oct 2015

  16. Pavy JJ, Denekamp J, Letschert J et al (1995) EORTC Late Effects Working Group. Late effects toxicity scoring: the SOMA scale. Int J Radiat Oncol Biol Phys 31(5):1043–1047

    Article  CAS  PubMed  Google Scholar 

  17. Schweizer MT, Zhou XC, Wang H et al (2013) Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy. Ann Oncol 24(11):2881–2886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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):197–209

    Article  CAS  PubMed  Google Scholar 

  19. 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):1794–1800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cimitan M, Bortulus R, Morassut S et al (2006) [18 F]fluorcholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients. Eur J Nucl Med Mol Imaging 33(12):1387–1398

    Article  PubMed  Google Scholar 

  21. Ceci F, Uprimny C, Nilica B et al (2015) (68)Ga-PSMA PET/CT for restaging recurrent prostate cancer: which factors are associated with PET/CT detection rate? Eur J Nucl Med Mol Imaging 42(8):1784–1794

    Article  Google Scholar 

  22. Merseburger AS, Hammerer P, Rozet F et al (2014) Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy. World J Urol 33(8):1079–1085

    Article  PubMed  PubMed Central  Google Scholar 

  23. Punnen S, Cooperberg MR, D’Amic AV et al (2013) Management of biochemical recurrence after primary treatment of prostate cancer: a systematic review of the literature. Eur Urol 64(6):905–915

    Article  PubMed  Google Scholar 

  24. Agarwal PK, Sadetsky N, Konety BR et al (2008) Treatment failure after primary salvage therapy for prostate cancer: likelihood, patterns of care, outcomes. Cancer 112(2):307–314

    Article  PubMed  Google Scholar 

  25. Yu EY, Gulati R, Telesca D et al (2010) Duration of first off-treatment interval is prognostic for time to castration resistance an death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation. J Clin Oncol 28(16):2668–2673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bhandari MS, Crook J, Hussain M (2005) Should intermittent androgen deprivation be uses routinely in clinical practice? J Clin Oncol 23(32):8212–8218

    Article  PubMed  Google Scholar 

  27. Jilg CA, Rischke HC, Reske SN (2012) Salvage lymph node dissection with adjuvant radiotherapy for nodal recurrence of prostate cancer. J Urol 188(6):2190–2197

    Article  CAS  PubMed  Google Scholar 

  28. Rischke HC, Schultze-Seemann, 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 191(4):310–320

    Article  PubMed  Google Scholar 

  29. Suardi N, Gandaglia G, Gallina A et al (2015) Long-term outcomes of salvage lymph node dissection for clinically recurrent prostate cancer: results of a single-institution series with a minimum follow-up of 5 years. Eur Urol 67(2):299–309

    Article  PubMed  Google Scholar 

  30. 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):191–197

    Article  PubMed  Google Scholar 

  31. Casamassima F, Masi L, Menichelli C et al (2011) Efficacy of eradicative radiotherapy for limited nodal metastases detected with choline PET scan in prostate cancer patients. Tumori 97(1):49–55

    CAS  PubMed  Google Scholar 

  32. Jereczek-Fossa BA, Beltramo G et al (2012) Robotic image-guided stereotactic radiotherapy, for isolated recurrent, lymph node or metastatic prostate cancer. Int J Radiat Oncol Biol Phys 82(2):889–897

    Article  PubMed  Google Scholar 

  33. Muacevic A, Kufeld M, Bist C et al (2011) Safety and feasibility of image-guided robotic radiosurgery for patients with limited bone metastases in prostate cancer patients. Urol Oncol 31(4):455–460

    Article  PubMed  Google Scholar 

  34. 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 metastasis. Acta Oncol 52(8):1622–1628

    Article  CAS  PubMed  Google Scholar 

  35. Ahmed KA, Barney BM, Davis BJ et al (2012) Stereotactic body radiation therapy in the treatment of oligometastatic prostate cancer. Front Oncol 22(2):215. doi:10.3389/fonc.2012.00215

    Google Scholar 

  36. Niyazi M, Bartenstein P, Belka C et al (2010) Choline PET based dose-painting in prostate cancer – modelling of dose effects. Radiat Oncol 18(5):23. doi:10.1186/1748-717X-5-23

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christoph Henkenberens M.D..

Ethics declarations

Conflict of interest

H.-J. Wester is the CEO of Scintomics. C. Henkenberens, C.A. von Klot, T.L. Ross, F.M. Bengel, A.S. Merseburger, J. Vogel-Claussen, H. Christiansen, and T. Derlin state that there are no conflicts of interest.

Ethical standards

The accompanying manuscript does not include studies on humans or animals.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henkenberens, C., von Klot, C.A., Ross, T.L. et al. 68Ga-PSMA ligand PET/CT-based radiotherapy in locally recurrent and recurrent oligometastatic prostate cancer. Strahlenther Onkol 192, 431–439 (2016). https://doi.org/10.1007/s00066-016-0982-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-016-0982-z

Keywords

Schlüsselwörter

Navigation