Background
Evidence-based guidelines for the management of systemic therapy–naïve oligometastatic renal cell carcinoma (RCC) are lacking.
Objective
To evaluate the potential of stereotactic ablative radiotherapy (SAbR) to provide longitudinal disease control while preserving quality of life (QOL) in patients with systemic therapy–naïve oligometastatic RCC.
Design, setting, and participants
RCC patients with three or fewer extracranial metastases were eligible. SAbR was administered longitudinally to all upfront and, as applicable, subsequent metastases.
Outcome measurements and statistical analysis
This prospective phase II single-arm trial was powered to achieve a primary objective of freedom from systemic therapy for >1 yr in >60% of patients (using the Clopper and Pearson methodology). Secondary endpoints included progression-free survival (PFS), defined as the time from first SAbR to progression not amenable to SAbR (local failure at SAbR-treated sites, new metastases not amenable to SAbR, more than three new metastases, or brain metastases); patient-reported QOL metrics; local control (LC) rates; toxicity; cancer-specific survival (CSS); and overall survival (OS).
Results and limitations
Twenty-three patients received SAbR to 33 initial and 57 total sites. The median follow-up was 21.7 mo (interquartile range 16.3–30.3). Exceeding the prespecified 60% benchmark, freedom from systemic therapy at 1 yr was 91.3% (95% confidence interval [CI]: 69.5, 97.8). One-year PFS was 82.6% (95% CI: 60.1, 93.1). QOL was largely unaffected. LC was 100%. There were no grade 3/4 toxicities, but there was one death due to immune-related colitis 3 mo after SAbR while on subsequent checkpoint inhibitor therapy, where a SAbR contribution could not be excluded. One-year OS was 95.7% (95% CI: 72.9, 99.4); one-year CSS was 100%.
Conclusions
SAbR for oligometastatic RCC was associated with meaningful longitudinal disease control while preserving QOL. These data support further evaluation of SAbR for systemic therapy–naïve oligometastatic RCC.
The current publication (Hannan et al) belongs to a prospective, randomised single-arm phase 2 trial on the effect of Stereotactic Body Radiotherapy (SBRT) (also known as stereotactic ablative radiotherapy (SAbR) in patients with oligometastatic (5 or less) renal cell carcinoma (mRCC) without systemic treatment.
A total of 23 patients were included. The primary endpoint was to evaluate long-term disease control (freedom from systemic disease) and quality of life (QoL). The study included mostly patients with metachronic metastatic disease on the favourable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification (74%) and lung metastasis (50%). Nephrectomy had been performed in 95% of cases.
In summary, the results demonstrate that over 90% of patients at 1 year were free of systemic treatment. In fact, the median time from primary tumour to SBRT was 32 months. Moreover, quality of life was not affected by SBRT-treatment and most patients were able to delay systemic treatment initiation; avoiding the complications associated with surgical resections.
Oligometastatic landscape for mRCC has been poorly evaluated. Like in other genitourinary cancer, definitions for oligometastatic remain unclear, however a couple of concepts are repeatedly reproduced in retrospective studies: patients undergoing complete resections and/or with a metachronous metastasis are reported to have improved survival outcomes (PMID: 31017089). The rational to use SBRT is based on a retrospective analysis and a meta-analysis that reported 90% local control rates with 1% added significant toxicities (PMID: 31302061). SBRT with very high doses per fraction in one to five fractions has been advocated to overcome the radioresistance of RCC. SBRT can lead to direct and rapid destruction of the tumour microvasculature and activation of additional apoptotic pathways that optimise cell death in RCC (PMID: 24694640).
This trial is a good start for future research in the field. A couple of items should be considered; firstly, the good prognosis of the vast majority of patients included (so that probably 1 year outcomes might be too short); secondly, active surveillance in the metastatic disease spectrum remains a safe option on well-selected subgroups (such as lung metastasis) (PMID: 27498080) to delay systemic treatment initiation as well.
The benefits and risks of adding SBRT to well-selected patients should be evaluated in a larger population of mRCC in a prospective manner.