Skip to main content

Advertisement

Log in

Clinical value of negative 68Ga-PSMA PET/CT in the management of biochemical recurrent prostate cancer patients

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the clinical value of 68Ga-PSMA PET/CT negativity in patients with biochemical recurrent prostate cancer (BCR).

Methods

One hundred three BCR patients (median age, 70 years; median PSA, 0.47 ng/mL) with negative 68Ga-PSMA PET/CT, followed up for at least 1 year, were retrospectively identified in a database of 1003 consecutive patients undergoing 68Ga-PSMA PET/CT for BCR. Clinical recurrence (CR) was determined or excluded on follow-up imaging selected as per clinical practice. Clinical recurrence-free survival (CRFS) was computed from the date of negative 68Ga-PSMA PET/CT to the date of evident disease; frequencies of CRFS were described as per ISUP patient subset (subset 1: ISUP grades 1 and 2; subset 2: ISUP grade 3; subset 3: ISUP grades 4 and 5) and other conventional variables.

Results

In 57 patients out of 103 (55.3%), CR was detected in the prostatic fossa (45.6%), nodes (38.6%), and bone (15.8%). The median CRFS was 15.4 months (range, 12.1–20.5), with a CRFS at 12 months in 61.4% of cases (range, 50.9–70.4) whereas the 24-month CRFS was 34.8% (range, 24–45.8). ISUP subset 1 benefited from significantly longer CRFS compared to subset 2 and subset 3 (median CRFS, 20.5 months, 12.6 months, and 12.1 months, respectively). ISUP subset 3 had significantly poorer 24-month CRFS (9.3%) compared to subset 1 (47.8%) and subset 2 (33.5%). At the univariate and multivariate analyses, the ISUP subset was the only significant risk factor for clinical relapse; ISUP subset 3 and subset 2 patients held a higher risk of CR compared to subset 1 patients (HR of 2.75 [1.35–5.57] for subset 3 versus subset 1; HR of 2.08 [1.11–3.88] for subset 2 versus subset 1).

Conclusion

68Ga-PSMA PET/CT negativity in early BCR patients (PSA < 0.5 ng/mL) with low-grade primary prostate cancer (ISUP1 and 2) may support the exploration of a clinical surveillance approach in future prospective studies.

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
Fig. 4

Similar content being viewed by others

References

  1. Antonarakis ES, Feng Z, Trock BJ, Humphreys EB, Carducci MA, Partin AW, et al. The natural history of metastatic progression in men with prostate-specific antigen recurrence after radical prostatectomy: long-term follow-up. BJU Int 60. 2012;109(1):32–9.

    Article  CAS  Google Scholar 

  2. Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol. 2007;25(15):2035–41.

    Article  Google Scholar 

  3. Stephenson AJ, Shariat SF, Zelefsky MJ, Kattan MW, Butler EB, Teh BS, et al. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA. 2004;291(11):1325–32.

    Article  CAS  Google Scholar 

  4. Stephenson AJ, Slawin KM, Bianco FJ Jr, Scardino PT. Perspectives on the natural history of recurrent prostate cancer after radical prostatectomy, based on the response to salvage radiotherapy. BJU Int. 2004;94(9):1210–2.

    Article  Google Scholar 

  5. Tendulkar RD, Agrawal S, Gao T, Efstathiou LA, Pisansky TM, Michalski JM, et al. Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol. 2016;34:3648–54.

    Article  Google Scholar 

  6. Stish BJ, Pisansky TM, Harmsen WS, Davis BJ, Tzou KS, Choo R, et al. Improved metastasis-free and survival outcomes with early salvage radiotherapy in men with detectable prostate-specific antigen after prostatectomy for prostate cancer. J Clin Oncol. 2016;34(32):3864–71.

    Article  Google Scholar 

  7. Pfister D, Bolla M, Briganti A, Carroll P, Cozzarini C, Joniau S, et al. Early salvage radiotherapy following radical prostatectomy. Eur Urol. 2014;65(6):1034–43.

    Article  Google Scholar 

  8. Siegmann A, Bottkeb D, Faehndricha J, Brachert M, Lohma G, Millerc K, et al. Salvage radiotherapy after prostatectomy - what is the best time to treat? Radiother Oncol. 2012;103(2):239–43.

    Article  Google Scholar 

  9. Treglia G, Mestre RM, Ferrari M, et al. Radiolabelled choline versus PSMA PET/CT in prostate cancer restaging: a meta-analysis. Am J Nucl Med Mol Imaging. 2019;9(2):127–39.

    PubMed  PubMed Central  Google Scholar 

  10. von Eyben FE, Picchio M, von Eyben R, Rhee H, Bauman G. Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography for prostate cancer: a systematic review and meta-analysis. Eur Urol Focus. 2018;4(5):686–93.

    Article  Google Scholar 

  11. Fendler WP, Calais J, Eiber M, et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical Trial. JAMA Oncol. 2019;5(6):856–63.

    Article  Google Scholar 

  12. Perera M, Papa N, Roberts M, 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;77:403–17.

    Article  Google Scholar 

  13. Wright GL, Haley C, Beckett ML, et al. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1(1):18–28.

    Article  Google Scholar 

  14. Emmett L, van Leeuwen PJ, Nandurkar R, Scheltema MJ, Cusick T, Hruby G, et al. Treatment outcomes from 68Ga-PSMA PET/CT-informed salvage radiation treatment in men with rising PSA after radical prostatectomy: prognostic value of a negative PSMA PET. J Nucl Med. 2017;58(12):1972–6.

    Article  CAS  Google Scholar 

  15. Emmett L, Tang R, Nandurkar RH, Hruby G, Roach PJ, Jo A, et al. 3-year freedom from progression following 68GaPSMA PET CT triaged management in men with biochemical recurrence post radical prostatectomy. Results of a prospective multi-center trial. J Nucl Med. 2020;61(6):866–872. https://doi.org/10.2967/jnumed.119.235028.

  16. Eder M, Neels O, Müller M, Bauder-Wüst U, Remdem Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: a new PET tracer for imaging of prostate cancer. Pharmaceuticals. 2014;7(7):779–96.

    Article  CAS  Google Scholar 

  17. Caroli P, Sandler I, Matteucci F, De Giorgi U, Uccelli L, Celli M, et al. PET/CT in patients with recurrent prostate cancer after radical treatment: prospective results in 314 patients. Eur J Nucl Med Mol Imaging. 2018;45(12):2035–44.

    Article  CAS  Google Scholar 

  18. Afshar-Oromieh A, Holland-Letz T, Giesel FL, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017 Aug;44(8):1258–68. https://doi.org/10.1007/s00259-017-3711-7.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Habl G, Sauter K, Schiller K, Dewes S, Maurer T, Eiber M, et al. For radiation treatment planning in prostate cancer recurrences after surgery: individualized medicine or new standard in salvage treatment. Prostate. 2017;77(8):920–7.

    Article  CAS  Google Scholar 

  20. Boreta L, Gadzinski AJ, Wu SY, Xu M, Greene K, Quanstrom K, et al. Location of recurrence by Gallium-68 PSMA-11 PET scan in prostate cancer patients eligible for salvage radiotherapy. Urology. 2019;129:165–71.

    Article  Google Scholar 

  21. 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. Jama. 2005;294(4):433–9.

    Article  CAS  Google Scholar 

  22. Paschalis A, Sheehan B, Riisnaes R, Rodrigues DN, Gurel B, Bertan C, et al. Prostate-specific membrane antigen heterogeneity and DNA repair defects in prostate cancer. Eur Urol. 2019. https://doi.org/10.1016/j.eururo.2019.06.030.

Download references

Acknowledgments

The authors wish to thank Cristiano Verna for editorial assistance and Grainne Tierney for language editing.

Funding

This study was partially funded by the Italian Ministry of Health, grant RF-2016-02364230, and by the Italian Association for Cancer Research (AIRC), grant IG 20476.

Author information

Authors and Affiliations

Authors

Contributions

Study concept and design: MC and FM

Provision of study materials or patients: MC, FM, PC, and UDG

Collection and assembly of data: MC and PC

Radiopharmaceutical synthesis and quality control: VDI

Statistical analysis: FF

Diagnostic imaging: MC, PC, VR, LF, and FM

Analysis and interpretation of data: MC, PC, GP, FM, and MG

Drafting of manuscript: MC

Critical revision of the manuscript for important intellectual content: FM and GP

All authors have read and approved the final manuscript.

Corresponding author

Correspondence to G Paganelli.

Ethics declarations

Ethical approval

The protocol was approved by the Ethics Committee of Area Vasta Romagna (IRST 185.02) and by the relevant Italian regulatory authorities. The study was performed in accordance with the principles of the 1964 Helsinki Declaration (and its later amendments) and the Good Clinical Practice.

Informed consent

All patients gave their written informed consent.

Conflict of interest

The authors declare that they have no conflicts of interest.

Data availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Publisher’s note

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

This article is part of the Topical Collection on Oncology - Genitourinary.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Celli, M., De Giorgi, U., Caroli, P. et al. Clinical value of negative 68Ga-PSMA PET/CT in the management of biochemical recurrent prostate cancer patients. Eur J Nucl Med Mol Imaging 48, 87–94 (2021). https://doi.org/10.1007/s00259-020-04914-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-020-04914-8

Keywords

Navigation