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ASTRO 2023

ASTRO 2023: Systemic Therapy and SABR in Metastatic RCC - Synergy and Side Effects

(UroToday.com) The 2023 American Society for Radiation Oncology (ASTRO) 65th Annual Meeting held in San Diego, CA between October 1st and 4th, 2023 was host to a session on stereotactic radiotherapy for renal cell cancer. Dr. Nicholas Zaorsky discussed the potential synergistic and adverse effects of systemic therapy use with stereotactic ablative radiotherapy (SABR) in patients with metastatic RCC.

Dr. Zaorsky began by noting that the incidence of RCC has doubled from 8 cases per 100,000 in the 1970s to 16 cases per 100,000 through the 2010s. However, the incidence of metastatic disease has remained unchanged at 2 cases per 100,000, which likely reflects the increased utilization of cross-sectional imaging in clinical practice with increased detection of these incidental renal masses. Furthermore, the mortality of RC in the general population has remained unchanged at 4 per 100,000 people.1
Over the last decade, SBRT has emerged as an option for the treatment of patients with RCC and has since been acknowledged by numerous guidelines, including the NCCN. What are the current data for SBRT in the metastatic setting? For the most part, such data is retrospective, although trials are now emerging in this setting. The local control rate appears to be approximately 90%, with grade 3+ toxicity of <1%. SBRT may be used in lieu of systemic therapy initially and may delay the time to systemic therapy by approximately 1 year. It may be curative for select patients. Furthermore, the cost is approximately $5,000 – $15,000 per course, significantly cheaper than systemic therapy (~$400,000 for tyrosine kinase inhibitors).

There is strong evidence for SBRT in other disease sites. SABR-COMET was a randomized, open-label phase II study of patients with oligometastatic disease (up to five sites) between February 2012 and August 2016. This trial included patients with prostate, lung, breast, and colorectal cancer. After stratifying by the number of metastases (1–3 vs 4–5), patients were randomized in a 1:2 fashion to receive either palliative standard of care alone or standard of care plus SABR. In an updated analysis published in 2020 (median follow up 51 months), the five-year OS rate was 17.7% (95% CI: 6-34%) in the control arm and 42.3% in the SBRT arm (95% CI: 28-56%, stratified log-rank p=0.006). The corresponding median OS was 28 months and 50 months, respectively. There were no new grade 2-5 adverse events and no differences in QOL between the arms.2,3

Looking specifically at SBRT for metastatic RCC, it appears that the local control rate is approximately 90% based on results from a meta-analysis published by Zaorsky et al. in 2019.sbrt for rcc metastasis
Importantly, the proportion of grade 3+ toxicity was only 1%, irrespective of site of irradiation. In 2021, Tang et al. published the results of a single arm, single center, feasibility trial that evaluated definitive radiotherapy in lieu of systemic therapy for patients with oligometastatic disease.4 This trial included 30 patients followed for a median of 17.5 months. The median number of metastatic sites was 1. The outcomes were as follows:

  • 1-year PFS: 64%, with a median PFS of 23 months
  • 1-year systemic-therapy free survival: 82%

systemic therapy survival
SBRT has recently also been evaluated in the oligoprogressive disease setting, whereby patients with evidence of oligoprogression following tyrosine kinase inhibitor treatment enrolled in a phase II trial evaluating SBRT in this setting. Cheung et al. demonstrated that the 1-year local control rate was 93%, and there was no grade 3 or worse toxicity from SBRT. The median time to change of systemic therapy was 12.6 months, and the 1-year overall survival was 92%.5 freedom from changing therapy
Recently, Hannan et al. published the results of a phase II trial that evaluated SBRT for patients with systemic therapy-naïve oligometastatic kidney cancer (n=23). At a median follow-up of 22 months, the freedom from systemic therapy rate at 1 year was 91%, and no patients had grade 3-4 toxicity.6freedom from systemic therapy
Given the available data, how do clinicians select therapy for patients with metastatic RCC? As of 2023, oncologists need better guidance with prognostication and tailored therapy. Currently, available tools include the STARS pan-cancer model that may help with metastatic prognostication and treatment selection:STARS pan cancer model
Another commonly available tool is the International Metastatic Database RCC Consortium (IMDC) risk stratification tool:survey table
Current trials evaluating the combination of systemic therapy and SBRT in the metastatic RCC setting are summarized in the table below:
trial table
Dr. Zaorsky concluded his presentation as follows:

  • From an epidemiologic perspective, metastatic RCC survival has not improved since the 1970s
  • Few modern treatments improve survival, and only in select patients
  • Oncologists need better guidance with risk stratification to select appropriate therapy

sbrt systemic therapy table
Presented by: Nicholas Zaorsky, MD, Associate Professor, Department of Radiation Oncology, Case Western Reserve University, University Hospitals, Cleveland, OH

Written By: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society for Therapeutic Radiation Oncology (ASTRO) 65th Annual Meeting held in San Diego, CA between October 1st and 4th, 2023 

References:
  1. Welch HG, Kramer BS, Black WC. Epidemiologic Signatures in Cancer. N Engl J Med. 2019;381:1378-86.
  2. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-2058.
  3. Palma DA, Olson R, Harrow S, et al. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020;38(25):2830-2838.
  4. Tang C, Msaouel P, Hara K, et al. Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial. Lancet Oncol. 2021;22(12):1732-9.
  5. Cheung P, Patel S, North SA, et al. Stereotactic Radiotherapy for Oligoprogression in Metastatic Renal Cell Cancer Patients Receiving Tyrosine Kinase Inhibitor Therapy: A Phase 2 Prospective Multicenter Study. Eur Urol. 2021;80(6):693-700.
  6. Hannan R, McLaughlin MF, Pop LM, et al. Phase 2 Trial of Stereotactic Ablative Radiotherapy for Patients with Primary Renal Cancer. Eur Urol. 2023;84(3):275-86.