In this pilot study, we have compared the diagnostic value of PSMA PET with conventional imaging such as CT in patients with metastatic RCC. In comparing the results of imaging to the histopathological reference from surgical excisional or biopsy samples, PSMA PET appears to provide comparable sensitivity and PPV over standard imaging modalities. It resulted in two patients having treatment modified based on the results. Moreover, it has the advantage of being able to be used in patients with renal impairment or contrast allergy where the administration may be contraindicated.
The greatest advantage of PSMA PET over standard CT is its ability to identify small lesions or lesions in areas where visualization is difficult such as in the liver especially when contrast cannot be used. According to the RECIST criteria 1.1, the dimensions of a malignant lymph node is defined as a node greater than 15 mm in short axis depending on the parts of the abdomen and pelvis [17]. Using PSMA PET, the smallest node identified was 6 mm with SUVmax of 3.1. Similarly, within the lung fields, we identified 34 lung lesions with the average short axis of 9.6 mm and SUVmax of 4.6. Unfortunately, there was only 1 histopathological sample from the lung fields available for correlation. Being able to identify sub-centimetre lesions may be important for patients with true oligometastatic disease or those with planned cytoreductive nephrectomy where the adjacent tumour deposits may be removed at the same time. In addition, lesions found outside surgical fields may be targeted using stereotactic ablative radiotherapy.
The evidence for using PSMA expression in the neovasculature of renal cell carcinoma deposits for imaging has been building recently. In a recent case series by Sawicki et al., the authors demonstrated in six patients the ability of 68Ga PSMA ligand and PET to detect metastatic lesion with high contrast; however, overall SUVmax was substantially lower in primary disease (0.2 ± 0.3) [20]. Using another PSMA-targeting ligand 18F-DCFPyL, Rowe et al. demonstrated superiority of the ligand over conventional imaging with similar sensitivity (94.7 %) in five patients [14]. Further, Gorin and Rowe et al. followed up the findings with the results from a rapid autopsy where seven of eight sites of radiotracer uptake that was not demonstrated on contrast enhanced CT were biopsied and confirmed to be positive for ccRCC.
PSMA is a functional enzyme that may have a role in developing neovasculature in solid tumours. Rowe et al., therefore, also considered the utility of SUVmax calculations in lesions as a prognostic indicator of response to systemic therapy such as tyrosine kinase inhibitors (TKI). For example, metastatic clear cell RCC patients are more likely to respond to TKI than with another subtype of RCC that are less likely to express PSMA. Using the same ligand, Gorin et al. performed a rapid autopsy after administration and found that all 98 % of CT-characterized lesions from a patient with metastatic disease were visualized on PET/CT with 12 further lesions being found. All histologically proven sites of ccRCC demonstrated PSMA expression [15]. Another ligand of interest is indium-111-labelled J591 anti-PSMA antibody. Pandit-Taskar et al. recently published the results of 5 case series of patients with metastatic RCC and 15 with other types of solid tumours in phase I clinical trial [21]. In the study, nodal lesion detection rate was 66 % in patients with metastatic RCC.
The current study aims to determine the clinical benefits of PSMA PET over standard imaging in patients with metastatic renal cell carcinoma. The study was limited in that not all the suspected metastatic lesions on CT and PET underwent histologic confirmation. Removing PET avid lesions selectively during surgery has introduced selection bias to the calculation of diagnostic values, and it is one of the major flaws of the study. Further, no reference standard for PET or CT negative lesions was used. Nevertheless, over one third of the suspected lesions had histologic confirmation and 11 out of 36 of these were false negative on CT imaging (with no false negatives on PET). In two patients, contrast CT was unable to be used due to renal impairment, potentially favouring the outcomes of PSMA PET in these cases.
It is also worth noting that PSMA expression is not specific to prostate or ccRCC. Therefore, caution must be exercised in interpreting the results in those with dual pathologies. Further, due to urinary excretion of 68Ga and PSMA expression in proximal tubules of kidney, there is limitation in using PSMA PET for detection and characterization of primary renal tumours.