Abstract
BackgroundCytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). As many patients are ineligible for major surgery, we hypothesized that SABR could be a safe alternative.MethodsIn this dose-escalation trial, inoperable mRCC patients underwent SABR targeting the entire affected kidney. Toxicity (CTCAE v3.0), quality of life (QoL), renal function, and tumour response (RECIST v1.0) were assessed.ResultsTwelve patients of mostly intermediate (67%) or poor (25%) International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class, median KPS of 70%, and median tumour size of 8.7 cm (range: 4.8–13.8) were enrolled in successive dose cohorts of 25 (n = 3), 30 (n = 6), and 35 Gy (n = 3) in 5 fractions. SABR was well tolerated with 3 grade 3 events: fatigue (2) and bone pain (1). QoL decreased for physical well-being (p = 0.016), but remained unchanged in other domains. SABR achieved a median tumour size reduction of − 17.3% (range: + 5.3 to − 54.4) at 5.3 months. All patients progressed systemically and median OS was 6.7 months. Crude median follow-up was 5.8 months.ConclusionsIn non-operable mRCC patients, renal-ablative SABR to 35 Gy in 5 fractions yielded acceptable toxicity, renal function preservation, and stable QoL. SABR merits further prospective investigation as an alternative to cytoreductive nephrectomy.Trial RegistrationClinicalTrials.gov NCT02264548. Registered July 22 2014 – Retrospectively registered: https://clinicaltrials.gov/ct2/show/NCT02264548
Highlights
Cytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma
Metastatic renal cell carcinoma represents one of the few clinical scenarios in which randomized evidence supports aggressive primary tumour control via cytoreductive nephrectomy (CN), as this is associated with improved overall survival when followed by interferon-based systemic
In a recent multi-institutional pooled analysis conducted by the International Radiosurgery Oncology Consortium for Kidney (IROCK), 223 patients were treated with systemicStereotactic ablative radiotherapy (SABR) targeting Renal cell carcinoma (RCC) primary tumours, yielding a local control rate of 97.8% at 2 years with Common Terminology Criteria for Adverse Events (CTCAE) ≥ Gr. 3 toxicity rate of 1.3% [16]
Summary
Cytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). Metastatic renal cell carcinoma (mRCC) represents one of the few clinical scenarios in which randomized evidence supports aggressive primary tumour control via cytoreductive nephrectomy (CN), as this is associated with improved overall survival when followed by interferon-based systemic. SABR is an emerging ablative modality for primary RCC tumours, achieving high rates of local control with minimal toxicity [14, 15]. In a recent multi-institutional pooled analysis conducted by the International Radiosurgery Oncology Consortium for Kidney (IROCK), 223 patients were treated with SABR targeting RCC primary tumours, yielding a local control rate of 97.8% at 2 years with CTCAE ≥ Gr. 3 toxicity rate of 1.3% [16]. We hypothesized that SABR may represent an alternative ablative modality for those patients who may otherwise have benefited from cytoreductive nephrectomy, but are medically inoperable or have unresectable primary tumours. Given recent evidence that SABR may stimulate anti-tumour immunity to increase sensitivity to contemporary immunotherapy [19,20,21], there is strong rationale to establish the safety of this technique, permitting its combination with immune checkpoint inhibitors to potentially enhance their effectiveness
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