Assessment with PSMA-PET Scan (PSMA Scan) Following Stereotactic Ablative Body Radiotherapy (SABR) for Renal Cell Carcinoma (RCC)

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APurpose/Objective SABR is an effective and safe treatment option for patients with localized RCC who are either medically or surgically inoperable 1-2. Current guidelines recommend six-monthly CT chest and abdomen scans as the standard method for assessing treatment response after SABR for RCC 3. However, while CT scans provide anatomical information, they do not assess pathological or metabolic changes in the tumour following treatment. Prostate specific membrane antigen (PSMA) is an angiogenic imaging marker for hypervascular tumours like RCC., PSMA PET scans have demonstrated potential in staging and restaging of RCC, according to several small retrospective case series.4-6. [GR1.1] The primary objective of this study was to investigate the role of PSMA PET in monitoring treatment response in patients who received SABR for localised RCC. A secondary objective was to evaluate efficacy of SABR and its impact on renal function. Materials/Methods A retrospective single institution series of 20 patients, who underwent 21 courses of SABR to the kidney at Genesiscare (GC), Fiona Stanley Hospital (FSH), Perth, Australia was included in this study. The study was approved by GC Research Committees. All patients were discussed in the Genitourinary Multidisciplinary Team meeting at FSH and were deemed medically or surgically unsuitable for partial or radical nephrectomy, leading to their referral for SABR. SABR was delivered via 3-5 fractions regimens of greater than 5 Gy per fraction. Eligible patients had no prior local ablative therapy and had a minimum 6 months follow-up after SABR. The primary endpoint was investigator-assessed tumour response by evaluating PSMA PET before SABR, and at multiple time points following SABR. Secondary endpoints included PSMA PET parameters and their correlations with tumour pathology, as well as evaluation of tumour size and renal function before and after SABR. Results Between June 2021 and October 2024, 25 patients with localized RCC were referred for SABR. Of these, 20 patients met the study’s inclusion criteria, with diagnostic biopsies conducted on 21 tumours before treatment. Histological analysis revealed 14 tumours as clear cell RCC, 6 as papillary RCC and one with inconclusive results. A total of 21 courses of SABR were administered, with dose regimens ranging from 32.5Gy in 5 fractions to 42Gy in 3 fractions. Median follow-up was 431 days (range, 61-1016 -). All patients except one (95%) were men, with a median age of 80 years (range, 51–89). Median and mean tumour diameters before SABR were 33 mm (range, 15-66) and 35.6 mm, respectively. At the last follow up, post SABR, median and mean tumour diameters were 30 mm (range, 13-64) and 36mm, respectively[EL2.1][TL2.2]. Median baseline estimated glomerular filtration rate (eGFR) was 61·0 mL/min per 1·73 m2 (range 23–90) and decreased by 9·05 mL/min per 1·73 m2 (range 0–24) by at least 6 months post-SABR. Baseline PSMA PET scans were performed for 20 of the SABR treatments. Four tumours (three papillary and one clear cell RCC) did not demonstrate PSMA binding. Among the 16 PSMA-binding tumours, seven patients showed an absence of PSMA binding at the last follow up, seven showed reduced binding, and two demonstrated stable binding.[EL3.1][TL3.2] Conclusions SABR is an effective and safe treatment option for patients with localized RCC who are medically or surgically inoperable. PSMA PET/CT surveillance imaging shows reduced binding in some but not all patients treated with SABR. The changes in PSMA binding are of uncertain clinical utility but may be a surrogate for treatment response. Prospective studies are warranted to further define its role and clinical utility.[GR4.1] References 1. Siva S, Ali M, Correa R, et al. 5-year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinomas: an individual patient data meta-analysis from IROCK (the International Radiosurgery Consortium of the Kidney). Lancet Oncol. 2022;23:1508-16. 2. Raj R, Upadhyay R, Wang S, Singer E, Dason S. Incorporating stereotactic ablative radiotherapy into the multidisciplinary management of renal cell carcinoma. Curr Oncol. 2023 Dec;30(12):10283-10298. 3. Siva S, Bressel M, Sidhom M, et al. Stereotactic ablative body radiotherapy for primary kidney cancer (TROG 15.03 FASTRACK II): a non-randomised phase 2 trial. Lancet Oncol. 2024;25(3):308-316. 4. Baccala A, Sercia L, Li J, Heston W, Zhou M. Expression of prostate-specific membrane antigen in tumour-associated neovasculature of renal neoplasms. Urology. 2007 Aug;70(2):385-90. 5. Raveenthiran S, Esler R, Yaxley J, Kyle S. The use of (68)Ga-PET/CT PSMA in the staging of primary and suspected recurrent renal cell carcinoma. Eur J Nucl Med Mol Imaging. 2019;46:2280-8. 6. Siva S, Callahan J, Pryor D, Martin J, Lawrentschuk N, Hofman M. Utility of (68)Ga prostate specific membrane antigen – positron emission tomography in diagnosis and response assessment of recurrent renal cell carcinoma. J Med Imaging Radiat Oncol. 2017

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