18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results

Abstract

Introduction Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. Methods 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. Results Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. Conclusion On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.

PSMA PET/CT in Renal Cell Carcinoma: An Overview of Current Literature

“…Several studies report the inclusion of patients affected by non-ccRCC [ 24 , 26 , 28 , 31 , 32 ], but larger case series regarding the performance of PSMA PET/CT in these patients remains very limited. Only one series has been published to date in which patients with papillary RCC ( n = 3), chromophobe RCC ( n = 2), unclassified RCC ( n = 2), and Xp11 translocation RCC ( n = 1) were included [ 33 ].…”

Application of 18F Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Monitoring Gastric Metastasis and Cancer Thrombi from Renal Cell Carcinoma

“…Endoscopic or surgical treatment can be used for single and early gastric metastasis [24]. Immunotherapy and/or targeted therapy can be used for multiple focal metastases or other organ metastases to improve patient survival [87][88][89][90]. e treatment of cancer thrombus requires a comprehensive evaluation and individualized therapy, including surgical resection, biological regulators, or targeted molecular therapy [87,91,92].…”

Role of PSMA-ligands imaging in Renal Cell Carcinoma management: current status and future perspectives

“…Despite growing interest in the clinical use of PSMA PET imaging for improved detection of RCC lesions, some limitations should be mentioned. In particular, small liver lesions below the resolution power of PET/CT (5 mm) as well as small lung metastases, due to free-breathing PET/CT acquisitions, might be overlooked (Ljungberg et al 2011;O'Connor et al 2012). However, novel technical improvements might overcome such limitations.…”

“…The first evidence in therapy response assessment was reported by Mittlmeier et al (2021) in 2021. Eleven patients with mccRCC performed [ 18 F]-PSMA PET/CT before starting Tyrosine Kinase Inhibitors (TKI) or Immune Checkpoints Inhibitors (ICI) and after 8 weeks of therapy.…”

“…In the last 50 years, a progressive increase of RCC diagnosis has been observed, in relation to the exposure to "modern" risk factors (e.g., obesity and alcohol consumption) and to the increased detection by new imaging modalities (Padala et al 2020;Tung and Sahu 2021). Indeed, kidneys are one of the most frequent sites of incidental findings, of which a non-negligible percentage is diagnosed as malignancies few years later (O'Connor et al 2012;Ballard and Guzman 2021).…”