Expert discusses expanding role of SBRT in metastatic renal cell carcinoma

The role of stereotactic body radiation therapy (SBRT) is expanding in renal cell carcinoma (RCC), highlighting the need for a focus on the proper management of the disease across a multidisciplinary approach, according to Raquibul Hannan, MD, PhD.

At the Society of Urologic Oncology 23rd Annual Meeting, Hannan, professor of radiation oncology, urology, and immunology, and chief of genitourinary radiation oncology at Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, discussed the role of SBRT in metastatic RCC.¹

“Historically, RCC had been considered to be very resistant, primarily to conventionally fractionated radiation. And since then, we have learned that with the advent of stereotactic radiation that gives us the ability to get a high dose of radiation in forms of primary and metastatic RCCs having local control rates over 90%,” Hannan explained. “So with this new modality, the onus is now really on us on how to integrate these in the proper management of metastatic RCC and to identify the patient that really benefits.”

Safety and efficacy of SBRT

First, Hannan evaluated the safety and efficacy of SBRT, also known as stereotactic ablative radiotherapy, in metastatic RCC among patients with spine and brain metastases.

In a trial conducted by Chiachien Jake Wang et al,² the researchers reviewed 175 lesions in 84 patients. They found a local control rate of 91% at a median of 16.7 months. Further, acute and late grade 3 toxicities occurred in 1.7% and 2.9% of patients, respectively. Hannan noted that factors associated with worse local control were spinal location, re-irradiation, dosimetry, and previous systemic therapy.

In another study that reviewed 28 studies,³ including 1602 patients with 3892 lesions who were treated with SBRT, local control at 1 year was 89% (95% CI, 83.6%-93.7%). Of note, any-grade adverse events (AEs) occurred in 0.7% of patients (95% CI, 0%-2.1%).

In 2 similar studies, 1 conducted by Taunk et al⁴ and 1 conducted by Kramer et al,⁵ local control occurred in 83% to 90% of those with spine metastases and in 84.3% to 100% of those with intracranial metastases.

“And this is a setting where we will work with the neurosurgeons to do surgery first followed by stereotactic radiation,” Hannan said.

SBRT in oligometastatic RCC

Next, Hannan focused on the role of SBRT in oligometastatic RCC following the evaluation of multiple studies in the space.

In a trial by Zhang et al,⁶ 47 patients with 88 disease sites were treated with SBRT, while sequential SBRT was also used to treat additional metastases. One-year and 2-year overall survival (OS) rates were 93.1% and 84.8%, respectively. Further, the median time from SBRT to the start of frontline systemic therapy was 15.2 months.

Similarly, in a more recent phase 2 trial of SBRT in oligometastatic RCC,⁷ 23 patients were enrolled and demonstrated a 1-year freedom from systemic therapy was 91.3%, 1-year progression-free survival (PFS) was 82.6%, and both 1-year cancer-specific survival and OS were 95.7%. Of note, the PFS has not yet been reached. Further, Hannan highlighted that there’s been no significant decline in quality of life, and only 3 patients experienced treatment-related AEs of grade 1.

In a prospective, registry-based, single-arm, observational, evaluation study,⁸ 1422 patients with 3 or more sites of metastases demonstrated a 1-year OS rate of 92.3%. Of those with metastatic RCC, the 1- and 2-year OS rates were 95.3% and 82.4%, respectively.

Lastly, a single-arm, single-center, feasibility, phase 2 trial⁹ showed that 30 patients with 5 or more sites of metastases who received sequential radiation had a median PFS of 22.7 months and a 1-year OS of 100%. Only 2 grade 3 and 1 grade 4 AE occurred.

“We are controlling the oligometastatic disease, but these patients for sure has oligometastatic disease, that we don't know if we're doing these patients a favor by delaying their systemic therapy and letting those oligometastases to progress,” Hannan said. “And this is why it is really important to design a phase 3 randomized trial looking at overall survival, which is what we're currently doing now.”

Hannan and colleagues are conducting the phase 3 EA8211 SOAR trial (NCT03796767),¹⁰ designed to evaluate the non-inferiority of SBRT vs systemic therapy in patients with oligometastatic RCC

SBRT in oligoprogressive RCC

Lastly, Hannan discussed the role of SBRT in oligoprogressive metastatic RCC across various studies.

In a trial of 51 patients with metastatic RCC with oligoprogression after SBRT, after a median follow-up of 19 months, median PFS was 16.3 months.¹¹

Similarly, a phase 2 prospective multicenter study¹² of a tyrosine kinase inhibitor plus SBRT in 37 patients demonstrated a local control rate of 93%. Further, median PFS was 9.3 months, and median time to change systemic therapy was 12.6 months. No grade 3 to 5 AEs were reported.

Lastly, another phase 2 trial¹³ of SBRT in oligoprogressive metastatic RCC showed that the approach extended ongoing systemic therapy by more than 6 months in 70% of patients (95% CI, 49.9%-90.1%). Median PFS was 24.4 months and the median extension of systemic therapy PFS was 11.1 months. Further, quality of life was unchanged, and only 1 grade 3 AE occurred.

References

1. Hannan R. The Role of SBRT in Metastatic RCC. Presented at: Society of Urologic Oncology (SUO) 23rdAnnual Meeting; November 30-December 2, 2022; San Diego, California.

2. Wang CJ, Christie A, Lin MH, et al. Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases. Int J Radiat Oncol Biol Phys. 2017;98(1):91-100. doi: 10.1016/j.ijrobp.2017.01.032.

3. Zaorsky NG , Lehrer EJ , Kothari G, Louie AV, Siva S. Stereotactic ablative radiation therapy for oligometastatic renal cell carcinoma (SABR ORCA): a meta-analysis of 28 studies. Eur Urol Oncol. 2019;2(5):515-523. doi: 10.1016/j.euo.2019.05.007.

4. NK Taunk, DE Spratt, M Bilsky, Y Yamada. Spine radiosurgery in the management of renal cell carcinoma metastases. JNCCN. 2015;13(6). doi:10.6004/jnccn.2015.0093.

5. Kramer K, Kushner BH, Modak S, et al. Compartmental intrathecal radioimmunotherapy: results for treatment for metastatic CNS neuroblastoma. J Neurooncol. 2010;97(3):409-18. doi:10.1007/s11060-009-0038-7.

6. Zhang Y , Schoenhals J, Christie A, et al. Stereotactic Ablative Radiation Therapy (SAbR) Used to Defer Systemic Therapy in Oligometastatic Renal Cell Cancer. Int J Radiat Oncol Biol Phys. 2019;105(2):367-375. doi: 10.1016/j.ijrobp.2019.07.023.

7. Hannan R, Christensen M, Robies L, et al. Phase II trial of stereotactic ablative radiation (SAbR) for oligometastatic kidney cancer. J Clin Oncol. 2021;39(6):311-311. doi:10.1200/JCO.2021.39.6_suppl.311.

8. Chalkidou A, Macmillan T, Grzeda MT, et al. Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: a prospective, registry-based, single-arm, observational, evaluation study. Lancet Oncol. 2021;22(1):98-106. doi:10.1016/S1470-2045(20)30537-4.

9. 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. 2021;22(12):P1732-1739. doi:10.1016/S1470-2045(21)00528-3.

10. Clinicaltrials.gov. Salvage Oligometastasectomy and Radiation Therapy in Recurrent Prostate Cancer (SOAR). https://clinicaltrials.gov/ct2/show/NCT03796767. Accessed: December 1, 2022.

11. Schoenhals JE, Mohamad O, Christie A,et al. Stereotactic Ablative Radiation Therapy for Oligoprogressive Renal Cell Carcinoma. Adv Radiat Oncol. 2021;6(5):100692. doi:10.1016/j.adro.2021.100692.

12. 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. doi:10.1016/j.eururo.2021.07.026.

13. Hannan R, Christensen M, Hammers H, et al. Phase II Trial of Stereotactic Ablative Radiation for Oligoprogressive Metastatic Kidney Cancer. Eur Urol Oncol. 2022;5(2):216-224. doi:10.1016/j.euo.2021.12.001.