For patients with renal cell carcinoma (RCC) who cannot undergo surgical resection, stereotactic ablative body radiation (SABR) represents a chance for cure. Despite the attractiveness of a non-invasive and well tolerated treatment that requires no incisions or hospitalization, the uptake of SABR for primary RCC has been slow worldwide.
A multi-institutional team of investigators from Australia has been at the vanguard of investigating the application of SABR, having published two cohorts of patients — FASTRACK I (from a Phase I study) and FASTRACK II (a phase II study) — indicating promising safety and outcomes for the treatment of medically inoperable RCC. Prior analyses from the International Radiosurgery Oncology Consortium for Kidney (iROCK) suggested that 5 fraction schedules were inferior to 1 and 3 fraction treatments in terms of treatment failure.
At this year’s ASTRO Annual Meeting, the FASTRACK team has combined the Phase I and II cohorts to obtain further insights for this combined cohort with regards to 1 and 3 fraction treatments. Patients were recruited in two periods from 2012 through 2020 and had to have biopsy proven RCC. Tumors that were smaller than 4 cm were treated with a single fraction of 26 Gy whereas those greater than 4 cm received 42 Gy in 3 fractions. Of the patients recruited, the mean RCC size was 4.7cm (SD +/- 1.1cm).
What the investigators found was promising. With 1 or 3 fraction SABR treatment, cancer control was excellent, with two-year local control of 100% and five-year control 99% (95% CI: 93-99%). Freedom from distant progression (FFDP) overall was also excellent, with two-year FFDP of 94.5% (95% CI:88.1%–98.1%) and five-year FFDP of 83.9% (95% CI:76.4% – 91.4%). Reflecting the health of these medically inoperable patients, five-year overall survival was 73.6% (95%CI: 65.1%–82.1%). Mean baseline eGFR was 59mL/min and the decline in eGFR at five-years post treatment was ~15.8 mL/min. Only one patient required dialysis. Highest grade of toxicity was Grade 3 and occurred in eight patients (7.8%), involving vomiting, chest wall or flank pain or colonic obstruction.
When asked whether this abstract would change minds of urologists who were still skeptical of SABR for the treatment of RCC, Shankar Siva, PhD, MBBS, of the Peter Macallum Cancer Centre, the lead author of the abstract, noted, “These studies were not designed to change urologists' minds! The data is compelling and should speak for itself, as robust prospective clinical trials investigating localized therapies in primary RCC are rare. Ultimately as patients and advocates become aware of the extraordinary efficacy of this totally non-invasive treatment, the community will demand access to SABR.”
Given the insights from this abstract, Dr. Siva and his co-investigators are planning the successor trial, FASTRACK III. FASTRACK III is proposed as a randomized trial of SBRT versus partial nephrectomy in T1a and T1b RCC. Dr. Siva comments, “This needs to be a multinational effort and requires considerable funding, so there is a lot of work to be done.” Randomized phase III studies that compare treatments of different modalities are notoriously difficult to complete. However, if successful, FASTRACK III could change clinical practice for the hundreds of thousands of patients worldwide who present with early and localized RCC.
Abstract 264, Ultra-Hypofractionated Stereotactic Ablative Body Radiotherapy (SABR) for Primary Renal Cell Carcinoma: Pooled Outcomes from the FASTRACK and FASTRACK II was presented during the SS 28 - GU 6: Revelations in Renal Radiotherapy session of the 67th ASTRO Annual Meeting.
