Skip to main content
Log in

Can PSMA-based tumor burden predict response to docetaxel treatment in metastatic castration-resistant prostate cancer?

  • Original Article
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

Purpose

We investigated the role of PSMA-derived tumor burden in predicting docetaxel (DTX) therapy response in metastatic castration-resistant prostate cancer (mCRPC).

Methods

Fifty-two mCRPC patients who received at least six cycles of DTX as the first-line treatment following 68Ga-PSMA PET/CT were enrolled in this retrospective study. Total PSMA-derived tumor volume (TV-PSMA) and total lesion PSMA activity (TL-PSMA) were derived from metastatic lesions. A ≥ 50% decline in PSA was defined as a response; a ≥ 25% increase in PSA was defined as progression. Univariate/multivariate logistic and cox regression analyses were performed to predict PSA response, OS, and TTP.

Results

Twelve (23%) patients had PSA progression after chemotherapy, while 40 patients (77%) achieved a PSA response. On univariate analysis, a significant association was found between TV-PSMA (p = 0.001), TL-PSMA (p = 0.001), pre-PSA (p = 0.012), LDH (p = 0.003), Hg (p = 0.035), and PSA response to DTX. High TV-PSMA (> 107 cm3) (p = 0.04) and high LDH (> 234 U/L) (p = 0.017) were 8.2 times and 12.2 times more likely for DTX failure in multivariate regression analyses. The median TTP was 16 months, and the median OS was not reached. Patients with high TV-PSMA (p = 0.017), high TL-PSMA (> 1013 cm3) (p = 0.042), high age (> 70 years) (p = 0.016), and high LDH (p ≤ 0.001) had significantly shorter OS, while only high TV-PSMA (p = 0.038) and high age (p = 0.006) were significantly related with shorter TTP. High TV-PSMA (p = 0.017) and high age (p = 0.01) were significant predictors for shorter OS, while only high age (p = 0.006) was a significant predictor for shorter TTP in multivariate analysis.

Conclusion

Patients with high TV-PSMA had a significantly higher risk for DTX failure. PSMA-based tumor burden prior to DTX therapy seems to be a reliable predictive tool for survival in mCRPC patients.

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. Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10:63.

    Article  CAS  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    CAS  Google Scholar 

  3. Bubendorf L, Schöpfer A, Wagner U, Sauter G, Moch H, Willi N, et al. Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol. 2000;31:578–83.

    Article  CAS  Google Scholar 

  4. Gravis G, Boher J-M, Fizazi K, Joly F, Priou F, Marino P, et al. Prognostic factors for survival in noncastrate metastatic prostate cancer: validation of the glass model and development of a novel simplified prognostic model. Eur Urol. 2015;68:196–204.

    Article  Google Scholar 

  5. Sweeney C, Chen Y, Liu G, Carducci M, Jarrard D, Eisenberger M, et al. Long term efficacy and QOL data of chemohormonal therapy (C-HT) in low and high volume hormone naïve metastatic prostate cancer (PrCa): E3805 CHAARTED trial. Ann Oncol. 2016;27:244.

    Article  Google Scholar 

  6. Glinsky GV, Glinskii AB, Stephenson AJ, Hoffman RM, Gerald WL. Gene expression profiling predicts clinical outcome of prostate cancer. J Clin Invest. 2004;113:913–23.

    Article  CAS  Google Scholar 

  7. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353–66.

    Article  Google Scholar 

  8. Mottet N, Cornford P, van den Bergh R. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer, version 2020.

  9. Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513–20.

    Article  CAS  Google Scholar 

  10. Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases. Urol. 1998;52:637–40.

    Article  CAS  Google Scholar 

  11. Rauscher I, Maurer T, Beer AJ, Graner F-P, 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;57:1713–9.

    Article  CAS  Google Scholar 

  12. Pyka T, Okamoto S, Dahlbender M, Tauber R, Retz M, Heck M, et al. Comparison of bone scintigraphy and 68Ga-PSMA PET for skeletal staging in prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2114–21.

    Article  CAS  Google Scholar 

  13. Han S, Woo S, Kim YJ, Suh CH. Impact of 68 Ga-PSMA PET on the management of patients with prostate cancer: a systematic review and meta-analysis. Eur Urol. 2018;74(2):179–90.

    Article  CAS  Google Scholar 

  14. Schmuck S, von Klot CA, Henkenberens C, Sohns JM, Christiansen H, Wester H-J, et al. Initial experience with volumetric 68Ga-PSMA I&T PET/CT for assessment of whole-body tumor burden as a quantitative imaging biomarker in patients with prostate cancer. J Nucl Med. 2017;58:1962–8.

    Article  CAS  Google Scholar 

  15. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402.

    Article  Google Scholar 

  16. Sanli Y, Kuyumcu S, Sanli O, Buyukkaya F, İribaş A, Alcin G, et al. Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer. Ann Nucl Med. 2017;31:709–17.

    Article  CAS  Google Scholar 

  17. Simsek DH, Sanli Y, Kuyumcu S, Engin MN, Buyukkaya F, Demirci E. Clinical impact of lower limb imaging in 68Ga-PSMA PET-CT for patients with prostate cancer. J Nucl Med Technol. 2019;47(3):233–7.

    Article  Google Scholar 

  18. Rowe SP, Pienta KJ, Pomper MG, Gorin MA. Proposal for a structured reporting system for prostate-specific membrane antigen–targeted PET imaging: PSMA-RADS version 1.0. J Nucl Med. 2018;59:479–85.

    Article  Google Scholar 

  19. Simsek DH, Sanli Y, Engin MN, Erdem S, Sanli O. Detection of metastases in newly diagnosed prostate cancer by using 68Ga-PSMA PET/CT and its relationship with modified D'Amico risk classification. Eur J Nucl Med Mol Imaging. 2020; p. 1–11.

  20. Werner RA, Bundschuh RA, Bundschuh L, Javadi MS, Higuchi T, Weich A, et al. Molecular imaging reporting and data systems (MI-RADS): a generalizable framework for targeted radiotracers with theranostic implications. Ann Nucl Med. 2018;32:512–22.

    Article  Google Scholar 

  21. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): five-year results of a randomized phase II trial. Am Soc Clin Oncol. 2020.

  22. Schick U, Jorcano S, Nouet P, Rouzaud M, Vees H, Zilli T, et al. Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases. Acta Oncol. 2013;52:1622–8.

    Article  CAS  Google Scholar 

  23. Schmidkonz C, Cordes M, Goetz TI, Prante O, Kuwert T, Ritt P, et al. 68Ga-PSMA-11 PET/CT derived quantitative volumetric tumor parameters for classification and evaluation of therapeutic response of bone metastases in prostate cancer patients. Ann Nucl Med. 2019;33:766–75.

    Article  CAS  Google Scholar 

  24. Schwarzenböck SM, Eiber M, Kundt G, Retz M, Sakretz M, Kurth J, et al. Prospective evaluation of [11 C] choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:2105–13.

    Article  Google Scholar 

  25. Sathianathen NJ, Philippou YA, Kuntz GM, Konety BR, Gupta S, Lamb AD, et al. Taxane-based chemohormonal therapy for metastatic hormone-sensitive prostate cancer: a Cochrane Review. BJU Int. 2019;124:370–2.

    Article  Google Scholar 

  26. Pond GR, Sonpavde G, De Wit R, Eisenberger MA, Tannock IF, Armstrong AJ. The prognostic importance of metastatic site in men with metastatic castration-resistant prostate cancer. Eur Urol. 2014;65:3–6.

    Article  Google Scholar 

  27. Halabi S, Kelly WK, Ma H, Zhou H, Solomon NC, Fizazi K, et al. Meta-analysis evaluating the impact of site of metastasis on overall survival in men with castration-resistant prostate cancer. J Clin Oncol. 2016;34:1652.

    Article  CAS  Google Scholar 

  28. Armstrong AJ, Garrett-Mayer ES, Yang Y-CO, De Wit R, Tannock IF, Eisenberger M. A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis. Clin Cancer Res. 2007;13:6396–403.

    Article  CAS  Google Scholar 

  29. Francini E, Petrioli R, Rossi G, Laera L, Roviello G. PSA response rate as a surrogate marker for median overall survival in docetaxel-based first-line treatments for patients with metastatic castration-resistant prostate cancer: an analysis of 22 trials. Tumor Biol. 2014;35:10601–7.

    Article  CAS  Google Scholar 

  30. Hiew K, Hart CA, Ali A, Elliott T, Ramani V, Sangar V, et al. Primary mutational landscape linked with pre-docetaxel lactate dehydrogenase levels predicts docetaxel response in metastatic castrate-resistant prostate cancer. Eur Urol Focus. 2019;5:831–41.

    Article  Google Scholar 

  31. Armstrong AJ, Garrett-Mayer E, De Wit R, Tannock I, Eisenberger M. Prediction of survival following first-line chemotherapy in men with castration-resistant metastatic prostate cancer. Clin Cancer Res. 2010;16:203–11.

    Article  CAS  Google Scholar 

  32. Beltran H, Tomlins S, Aparicio A, Arora V, Rickman D, Ayala G, et al. Aggressive variants of castration-resistant prostate cancer. Clin Cancer Res. 2014;20:2846–50.

    Article  CAS  Google Scholar 

  33. Nadal R, Schweizer M, Kryvenko ON, Epstein JI, Eisenberger MA. Small cell carcinoma of the prostate. Nat Rev Urol. 2014;11:213.

    Article  CAS  Google Scholar 

  34. Halabi S, Lin C-Y, Small EJ, Armstrong AJ, Kaplan EB, Petrylak D, et al. Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy. J Natl Cancer Inst. 2013;105:1729–37.

    Article  CAS  Google Scholar 

  35. Cook RJ, Coleman R, Brown J, Lipton A, Major P, Hei YJ, et al. Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res. 2006;12:3361–7.

    Article  CAS  Google Scholar 

  36. Zou Q, Jiao J, Zou M-H, Li M-Z, Yang T, Xu L, et al. Semi-automatic evaluation of baseline whole-body tumor burden as an imaging biomarker of 68 Ga-PSMA-11 PET/CT in newly diagnosed prostate cancer. Abdom Radiol. 2020;45(12):4202–13.

    Article  Google Scholar 

  37. Seifert R, Kessel K, Schlack K, Weber M, Herrmann K, Spanke M, et al. PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [177 Lu] Lu-PSMA-617 radioligand therapy in a bicentric analysis. Eur J Nucl Med Mol Imaging. 2020; p. 1–11.

  38. Bieth M, Krönke M, Tauber R, Dahlbender M, Retz M, Nekolla SG, et al. Exploring new multimodal quantitative imaging indices for the assessment of osseous tumor burden in prostate cancer using 68Ga-PSMA PET/CT. J Nucl Med. 2017;58:1632–7.

    Article  CAS  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Duygu Has Simsek.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Has Simsek, D., Kuyumcu, S., Karadogan, S. et al. Can PSMA-based tumor burden predict response to docetaxel treatment in metastatic castration-resistant prostate cancer?. Ann Nucl Med 35, 680–690 (2021). https://doi.org/10.1007/s12149-021-01610-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12149-021-01610-x

Keywords

Navigation