Role of ⁶⁸Ga-PSMA-11 PET/CT in early response prediction to anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma

RCC is a highly vascular tumor and anti-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors targeting tumor neoangiogenesis form the first-line therapy of metastatic RCC (mRCC). Owing to the cytostatic nature of these drugs, structural changes require many months to develop and lead to underestimation of treatment response on CT using RECIST 1.1. There is an unmet need for better markers to predict and assess treatment response earlier to avoid unnecessary costs and side effects in non-responders. Although ¹⁸F-FDG has shown promising results, other angiogenic imaging tracers such as ⁶⁸Ga-PSMA-11, are also being evaluated. This study aims to assess the role of ⁶⁸Ga-PSMA-11 PET/CT as an angiogenesis imaging marker in predicting early response to anti-VEGFR TKI therapy in mRCC and compare it with the CT-based RECIST criteria at three months. Patients diagnosed with metastatic RCC on preliminary workup and planned to undergo TKI therapy were enrolled in this prospective study. After taking informed consent, ⁶⁸Ga-PSMA-11 PET/CT scans were acquired at baseline, at one and three months after the start of therapy. PET/CT images were analysed qualitatively and quantitatively using parameters: SUVmax, SUVmean, SUVpeak, PSMA-derived Tumour Volume (PSMA-TV), and Total Lesion PSMA (TL-PSMA). The PET-based response was assessed using modified PERCIST criteria, and the CT-based response using RECIST criteria 1.1. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 26.0. A total of 27 patients were included in the final analysis. Twenty-one (77%) and four (15%) patients had clear cell and papillary RCC, respectively; while eosinophilic variant and collecting duct RCC were observed in one (4%) patient each. Treatment responders [complete response (CR) and partial response (PR)] based on RECIST 1.1 had a higher baseline SUVmax (13.9 vs 8.1, p = 0.07), SUVmean (10.2 vs 5.7, p = 0.11) and SUVpeak (9.7 vs 5.7, p = 0.12) uptake than non-responders, however no statistically significant difference was observed. PET at one-month post- treatment revealed PR in 25 of 27 (~93%) patients, SD in one patient (~4%), while in one patient, SUVmean of target lesions at baseline showed a decrease of ~73%; however, a new brain lesion appeared, amounting to an overall disease progression (PD). CT at three months revealed PR in nine patients (~33%), SD in 14 patients (~52%), and PD in four patients (~15%). The PET response at one month and CT response at three months were discordant in 16 of 27 patients (~59%), with a significant disagreement and poor concordance between the two (k = 0.08, p = 0.3) modalities. Early response assessment to tyrosine kinase inhibitor therapy is feasible using ⁶⁸Ga PSMA-11 PET-CT in metastatic RCC, and response assessment on PSMA PET using modified PERCIST shows significant disagreement with CT at three months using RECIST 1.1. (author)