Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer

Abstract

Purpose: Since the introduction of PSMA PET/CT with 68Ga-PSMA-11, this modality for imaging prostate cancer (PC) has spread worldwide. Preclinical studies have demonstrated that short-term androgen deprivation therapy (ADT) can significantly increase PSMA expression on PC cells. Additionally, retrospective clinical data in large patient cohorts suggest a positive association between ongoing ADT and a pathological PSMA PET/CT scan. The present evaluation was conducted to further analyse the influence of long-term ADT on PSMA PET/CT findings.

Methods: A retrospective analysis was performed of all 1,704 patients who underwent a 68Ga-PSMA-11 PET/CT scan at our institution from 2011 to 2017 to detect PC. Of 306 patients scanned at least twice, 10 had started and continued ADT with a continuous clinical response between the two PSMA PET/CT scans. These ten patients were included in the current analysis which compared the tracer uptake intensity and volume of PC lesions on PSMA PET/CT before and during ongoing ADT.

Results: Overall, 31 PC lesions were visible in all ten patients before initiation of ADT. However, during ongoing ADT (duration 42-369 days, median 230 days), only 14 lesions were visible in eight of the ten patients. The average tracer uptake values decreased in 71% and increased in 12.9% of the PC lesions. Of all lesions, 33.3% were still visible in six patients with a complete PSA response (≤0.1 ng/ml).

Conclusion: Continuous long-term ADT significantly reduces the visibility of castration-sensitive PC on PSMA PET/CT. If the objective is visualization of the maximum possible extent of disease, we recommend referring patients for PSMA PET/CT before starting ADT.

Keywords: 68Ga-PSMA-11; Androgen deprivation therapy; PET/CT; PSMA; Prostate cancer; Prostate-specific membrane antigen.

Conflict of interest statement

Ethical approval

All patients discussed in this article provided signed informed consent for the anonymized evaluation and publication of their data. All reported investigations were conducted in accordance with the principles of the Declaration of Helsinki and with our national regulations (German Medicinal Products Act, AMG section 13 2b). This evaluation was approved by the Ethics Committee of the University of Heidelberg (S-321-2012).

Conflicts of interest

None.

Figures

Fig. 1

Patient selection flow chart

Fig. 2

The majority of PC lesions show clearly decreasing average tracer uptake (SUVmean, top) and tracer uptake to tumour volume ratios (bottom) during ongoing ADT. No bars are shown for those lesions that were no longer visible during ongoing ADT (on PET-2) or for those lesions without a clear morphological correlate in CT (impossible volume measuring). SUVmean values for the cut bar (number 3) were 20.3 on PET-1 and 27.2 on PET-2. Lesion allocations: lesions 1 and 2 (patient 1), lesions 3 and 4 (patient 2), lesions 5–9 (patient 3), lesions 10–14 (patient 4), lesion 15 (patient 5), lesions 16–18 (patient 6), lesion 19 (patient 7), lesions 20–25 (patient 8), lesions 26–30 (patient 9) and lesion 31 (patient 10)

Fig. 3

The majority of PC lesions show clearly decreasing maximum tracer uptake (SUVmax, top) and tracer uptake to tumour volume ratios (bottom) during ongoing ADT. No bars are shown for lesions that were no longer visible during ongoing ADT (on PET-2)

Fig. 4

Lymph node metastasis in an example patient (patient 8; yellow arrows) without ADT (a, b) and during ongoing ADT with a complete PSA response (c, d) 190 days after the first scan. During ongoing ADT, both, tracer uptake intensity and tumour volume significantly decreased. a Fused PET and CT image without ADT. b Maximum intensity projection image of the PET data without ADT. c Fused PET and CT image during ongoing ADT. d Maximum intensity projection image of the PET data during ongoing ADT

Fig. 5

Lymph node metastasis in an example patient (patient 9) without ADT (a–c) and during ongoing ADT with a complete PSA response (d–f) 228 days after the first scan (orange arrow left ureter). a Low-dose CT image without ADT. b Fused PET and CT image without ADT. c Maximum intensity projection image of the PET data without ADT. d–f same as a–c but during ongoing ADT

Fig. 6

Bone metastasis in an example patient (patient 1; yellow arrows) without ADT (a, b) and during ongoing ADT (c, d) 323 days after the first scan. a Fused PET and CT image without ADT. b Maximum intensity projection image of the PET data without ADT. c Fused PET and CT image during ongoing ADT. d Maximum intensity projection image of the PET data during ongoing ADT

Fig. 7

A PSA response to ADT was observed in all patients (top). A complete imaging response (negative PSMA PET/CT) was observed in patient 4 and 10 although more patients showed a complete PSA response (BIC bicalutamide, LEU leuprorelin, TRI triptorelin)

Fig. 8

Bone metastasis in an example patient (patient 6; yellow arrows; lesion 16 in Fig. 2) visible on both PET-1 and PET-2 with similar tracer uptake despite a complete PSA response (0.01 ng/ml) to ADT (a, b PET-1 without ADT; c, d PET-2 during ongoing ADT 270 days after the first scan). a Fused PET and CT image without ADT. b Low-dose CT image without ADT. c Fused PET and CT image during ongoing ADT. d Low-dose CT image during ongoing ADT

Fig. 9

Lymph node metastasis in an example patient (patient 9; yellow arrows) clearly visible on PET-1 without ADT (a, b) which became significantly less visible on PET-2 with a complete PSA response to ADT (c, d). a Fused PET and CT image without ADT. b Maximum intensity projection image of the PET data without ADT. c Fused PET and CT image during ongoing ADT. d Maximum intensity projection image of the PET data during ongoing ADT