68Ga-PSMA-11 PET/CT Follow-Up of Patients with Prostate Cancer with Bone Metastases Who Had Reduced Bone Density after Androgen Deprivation Therapy

Abstract

Bone metastases from prostate cancer (PCa) often show an increase in density on computed tomography (CT) after successful androgen deprivation therapy (ADT). Density may be reduced, however, as the disease progresses or, contrarily, when disease is no longer active. The current study investigated the role of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in differentiating between these two conditions. Methods: The study cohort included 15 PCa patients with sclerotic/blastic bone metastasis in whom reduction in bone density of metastasis was noted on follow-up 68Ga-PSMA-11 PET/CT after ADT. Each patient had two PET/CT scans. Prior to the first scan, six patients were castration naïve and nine patients were already treated. All patients had ADT between the two PET/CT scans. PET parameters (SUVmax and tumor-to-background ratio), and CT parameters (HUmax) were determined and compared for each lesion on both scans. Patient’s response was based on prostate-specific antigen (PSA) levels and appearance of new lesions. The Kolmogorov–Smirnov test was used to evaluate normal distribution of the continuous variables. Results: Post-ADT reduction in bone density was identified in 37 lesions. The mean HUmax was 883.9 ± 175.1 on the first scan and 395.6 ± 157.1 on the second scan (p < 0.001). Twenty-one of the 37 lesions showed no increased tracer uptake on the second PET/CT scan raising the likelihood of a response. The other 16 lesions were associated with increased uptake suggestive of an active resistant disease. Bone density was not different in lesions that no longer showed an increased uptake as compared with those that did. Seven of the study patients responded to therapy, and none of the 16 lesions found in these patients showed increased 68Ga-PSMA-11 uptake. In eight patients with progressive disease, all 12 lesions in five of them showed increased 68Ga-PSMA-11 uptake, there was mixed response in two patients (having two lesions with increased uptake and one without) and although all three lesions no longer showed an increased uptake, new lesions were detected in the eighth patient. Conclusion: A decrease in density of bone lesions may reflect clinical progression, or contrarily, a response to therapy in patients with PCa and skeletal involvement treated with ADT. Uptake of 68Ga-PSMA-11 may separate between these two vastly opposing conditions.

PSMA-PET follow-up to assess response in patients not receiving PSMA therapy: Is there value beyond localization of disease?

“…Unlike our results, they observed a significant correlation with PSA trends, likely due to their access to detailed patient data throughout the therapy . This indicates the relevance of PSMA-PET for response assessment, which seems to be effective also in early stages of prostate cancer not only to localize disease, but also to assess the patient's risk 25 , 26 . In this regard, PSMA-PET appears to be well-suited for assessing response to systemic non-RLT therapies, including chemotherapy and hormone therapy 27 - 29 .…”

Nuclear medicine imaging for bone metastases assessment: what else besides bone scintigraphy in the era of personalized medicine?

“…Similar to how an increase in the density of sclerotic bone metastases can be associated with either a therapeutic response or progression, studies in prostate cancer under androgen deprivation therapy have found that a decrease in the density of initially sclerotic bone metastases and a reduction in the uptake of bone-targeting agents can also be indicative of both scenarios (Figure 1) (38,39). This may be attributed to the suppression of the osteoblastic effect of testosterone in the event of a therapeutic response or the progression towards predominant lytic phenomena following the acquisition of resistance to hormonal therapy (38). In prostate cancer, this limitation could be overcome by the advent of radiolabeled PSMA PET/CT.…”

“…In a retrospective analysis involving prostate cancer patients receiving androgen deprivation therapy, findings revealed that among the 65 patients with bone metastases who underwent 68 Ga-PSMA PET/CT scans, 15 individuals (23%) displayed a decrease in the density of their bone metastases. Among the 37 lesions that exhibited reduced density, 21 (57%) were negative on PET scans, while 16 (43%) had intense 68 Ga-PSMA uptake ( 38 ). Significantly, PET scans did not detect any positive findings in the bone lesions of patients who exhibited a treatment response.…”

On the Way for Patients with Prostate Cancer to the Best Use of PSMA

“…The present issue of the International Journal of Molecular Sciences ( IJMS ) includes publications on staging using PSMA PET for the initial management of patients with prostate cancer [ 11 ] and on restaging using PSMA PET/CT for patients with prostate cancer at PSA relapse [ 12 , 13 , 14 , 15 ]. Other publications report the impact of the chemical structure of small inhibitory molecules for the PSMA receptor [ 16 ], animal models of PSMA and prostate cancer [ 17 ], and associations between the androgen receptor signal transduction pathway and the expression of PSMA [ 18 , 19 , 20 ].…”