Non-randomised trial evaluates SABR for medically inoperable or high-risk primary renal cell cancer

Evidence before this study

Renal cell carcinoma is perceived to be a radioresistant disease. Surgery is the preferred treatment for a primary renal cellcancer in patients who are medically operable and withresectable tumours; however, many older patients havecomorbidities that preclude them from surgical intervention. Although percutaneous thermal ablation has been describedas an alternative intervention for small renal masses, thistechnique has several technical limitations and there is anabsence of published clinical trial evidence to support its use. Therefore, patients with primary renal cell cancer who aremedically inoperable or at high risk of surgical complications, particularly those with larger renal masses, have limitedcurative treatment options. It is in this context that stereotactic ablative body radiotherapy (SABR) is emerging as a novel, non-invasive curative treatment option for primary renal cell cancer. We searched PubMed and Embase for research articles published in English between Jan 1, 1995, and April 5, 2023, with the search string: (“radiotherapy” OR “radiation therapy” OR “stereotactic” OR “cyberknife” OR “sabr” OR “sbrt”) AND (“Kidney neoplasms” OR “kidney neoplasm” OR “renal neoplasms” OR “kidney cancer” OR “renal cell carcinoma” OR ““carcinoma, renal cell” OR “renal cell cancer” OR “renal adenocarcinoma”) AND (english[Filter]). Although several retrospective studies, systematic reviews, and meta-analyses of SABR for primary renal cell cancer have been published, prospective clinical trial evidence for SABR so far has been confined to small, single-centre trials.

Added value of this study

To our knowledge, TROG 15.03 FASTRACK II is the first multicentre clinical trial of a non-surgical definitive therapy for primary renal cell cancer. This non-randomised trial enrolled patients with medically inoperable or technically high-risk primary renal cell cancer across eight centres in Australia and the Netherlands. Despite a larger average tumour size (4·6 cm) than in many pre-existing prospective trials of surgery or SABR in primary renal cell cancer, there were no local treatment failures observed and no patients died from cancer during the study period. Few treatment-related toxicities and limited renal function decline were noted. Notably, the tumours that were treated were larger and more complex than could be expected to be effectively treated with thermal ablation approaches.

Implications of all the available evidence

Taken together, the results of FASTRACK II along with previous single-centre clinical trials support SABR as a therapeutic option for patients with inoperable or high-risk primary renal cell cancer. Renal function preservation and the associated toxicity profile appears acceptable. The observed exceptional oncological outcomes justify the design of a randomised controlled trial of surgery versus SABR for patients with primary renal cell cancer.

Source: The Lancet Oncology