Abstract
Simple SummaryProstate-specific membrane antigen (PSMA) is regularly overexpressed in prostate cancer cells. Radioligand therapy (RLT) targeting PSMA has shown impressive results in recent years in treatment of metastatic castration-resistant prostate cancer (mCRPC). In some patients, however, the disease worsens during PSMA-RLT. A proportion of these patients develop a type of metastasis that has intense glucose metabolism but missing or low PSMA expression; these metastases are referred to as ‘mismatch metastases’. We found that combined PET imaging using the radiolabeled glucose analog [18F]FDG and the PSMA radioligand [68Ga]Ga-PSMA-11 is essential to identify patients with mismatch findings, which are associated with significantly worse outcome, especially if the mismatch is located in the liver or of high volume. Consequently, additional treatments or change to another treatment modality appears necessary.Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC), some patients show worsening disease during PSMA-RLT. We investigated the value of combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging in this setting. In n = 29 mCRPC patients with worsening disease after a median of four cycles of [177Lu]Lu-PSMA-617 RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging was performed to detect [18F]FDG-avid lesions with low or no PSMA expression (mismatch lesions). To evaluate prognostic implication of mismatch, survival analyses regarding presence, location, and [18F]FDG PET-derived parameters such as SUVmax, metabolic tumor volume (MTVm), and total lesion glycolysis (TLGm) of mismatch findings were performed. Seventeen patients (59%) showed at least one mismatch metastasis. From the time point of combined PET imaging, the median overall survival (OS) of patients with mismatch findings was significantly (p = 0.008) shorter than those without (3.3 vs. 6.1 mo). Patients with a high MTVm revealed a significantly (p = 0.034) shorter OS of 2.6 mo than patients with low MTVm (5.3 mo). Furthermore, patients with hepatic mismatch showed a significantly (p = 0.049) shorter OS than those without (2.9 vs. 5.3 mo). Difference in OS regarding SUVmax and TLGm was not significant. In mCRPC patients with worsening disease during PSMA-RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging is essential to identify mismatch findings, as these are associated with poor outcomes requiring a change in therapy management.
Highlights
Prostate cancer is one of the most common malignancies in men, with over 1,200,000 new cases and approximately 359,000 deaths worldwide in 2018 [1]
Out of n = 29 metastatic castration-resistant prostate cancer (mCRPC) patients included in this retrospective study, 17/29 (59%)
Patients showed at least one mismatch metastasis in combined [18 F]FDG and [68 Ga]GaPSMA-11 positron emission tomography (PET) imaging, whereas 12/29 (41%) patients did not show any mismatch findings
Summary
Prostate cancer is one of the most common malignancies in men, with over 1,200,000 new cases and approximately 359,000 deaths worldwide in 2018 [1]. Despite the promising results of PSMA-RLT, some patients do not exhibit a sufficient response, and others with initially good responses experience a worsening disease in the course of PSMA-RLT [16,17] Some of those patients with worsening disease develop lesions with missing or low PSMA expression. Mostly prostate carcinoma cells have a low glucose metabolism due to energy gain by lipids and other energetic molecules, in advanced mCRPC the glucose metabolism is very heterogeneous and can be highly increased by shifting to aerobic glycolysis after numerous mutation events [20] Such lesions with intense glucose metabolism on [18 F]FDG PET/CT but missing or low PSMA expression, so-called ‘mismatch findings’, may be insufficiently affected by PSMA-RLT, and may necessitate a change in therapy management. Little is known about the impact of the development and value of diagnosing mismatch findings during treatment
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