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



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


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.


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).


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.

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


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




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.

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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.

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All patients gave their written informed consent.

Conflict of interest

The authors declare that they have no conflicts of interest.

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

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

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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 (2020).

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  • 68Ga-PSMA PET/CT
  • Negative PSMA
  • Biochemical recurrence
  • Prostate cancer