RADIOLOGY CORNER Stereotactic Ablative Radiation for Primary Renal Cell Carcinoma: A Promising Alternative
By: Mohannad A. Awad, MD, MAS, University of Texas Southwestern, Dallas; Raquibal Hannan, MD, PhD, University of Texas Southwestern, Dallas; Jeffrey A. Cadeddu, MD, FRCS(Glasg), University of Texas Southwestern, Dallas | Posted on: 19 Sep 2023
An 83-year-old gentleman with a history of intermediate-risk prostate cancer that was treated with definitive external beam radiation therapy 6 years ago presented with hematuria and underwent a full workup, which was negative aside from a right renal cyst and an incidental 1.7-cm enhancing left upper pole renal mass that was suspicious for renal cell carcinoma (RCC). After discussion with the patient, he was placed on active surveillance. Interval imaging in 6 months showed an increase in size of the mass to 2.1 cm. Interval imaging at 12 months revealed the mass increased in size to 3.1 cm in greatest diameter, extending to the renal sinus (Figure 1).
Treatment options were discussed with the patient and, given his age, life expectancy, and refusal to undergo any anesthesia, he elected to proceed with stereotactic ablative radiation (SAbR). He underwent a renal mass biopsy, which confirmed clear cell RCC, International Society of Urological Pathology nucleolar grade 2/4. A renal scan revealed split function of 53% to the left kidney. He then received the SAbR of 3600 cGy, delivered in 3 fractions of 1,200 cGy each (Figure 2). He tolerated the procedure well with mild (grade 1) fatigue.
He was followed with interval abdominal imaging every 6 months, which showed initial stability followed by a steady decline in tumor size, which stabilized to 1.1-cm scar tissue by 3 years (Figure 3). Interestingly, the mass continued to enhance. A repeat renal mass biopsy 1 year post-SAbR showed hyalinization, necrosis, and significantly decreased cellularity with rare intact tumor cells that did not express Ki67, suggesting nonproliferation.
The last CT scan in 5 years post-SAbR showed left renal scarring, with central area of heterogeneous enhancement measuring 1.1 cm, which is not changed from the CT scan done a year prior (Figure 4). At last follow up 5.5 years post-SAbR he is doing well clinically without any side effects. His creatinine and glomerular filtration rate remain stable at 1.1 mg/dL and 61 mL/min/1.73 m2, respectively.
Radiation therapy has historically been considered ineffective for treating RCC, possibly due to the radio-resistance to conventional radiation and limitations in radiation delivery. Treating kidney tumors poses technical challenges, including limited tolerance of the surrounding radiosensitive organs at risk (ie, small bowel), and difficulties in precisely targeting a tumor that is constantly moving with respiration.
SAbR is a modern treatment technique that delivers a highly precise and focused dose of radiation to the target, either in a single or few fractions.1 Unlike conventional radiation techniques, SAbR uses multiple technological advances such as intensity modulation, image guidance, motion tracking or motion gating which compensates for respiratory movement and allows accurate radiation delivery. This enables the application of high-dose radiation precisely to the tumor, effectively ablating it while minimizing radiation dose to the nearby organs and maximally preserving overall renal function.2
Early studies on animals and small patient groups have shown the feasibility and safety of SAbR for renal tumors, with complete necrosis within the targeted area and no damage to adjacent tissues.2,3 A multi-institutional retrospective study by the International Radiosurgery Consortium of the Kidney involving 190 patients with primary RCC treated with SAbR with a median follow-up of 5 years showed a 5.5% local failure rate. The estimated 3-year, 5-year, and 7-year cancer-specific survival were 95.5%, 92%, and 92%, respectively.4 A recent large review of 87 studies that included 589 primary RCCs revealed a local control (LC) rate of more than 90%.5 Most of these studies focused on radiographic LC. Interestingly, as was observed in the above case, tumor enhancement on CT post-SAbR is typically not changed, suggesting that the long-term effect of SAbR does not disrupt the vasculature or tissue architecture within the tumor, as may be expected from other ablation techniques. The pathologic evidence of radiation effects, nonproliferation, and induction of terminal replicative arrest were recently demonstrated in one of the first prospective phase 2 trials of SAbR for primary RCC that enrolled 16 patients and reported a LC of 94.5% at 3 years. One-year post-SAbR tumor biopsy revealed radiation effects of reduced cellularity, hyalinization, and necrosis. Immunohistochemistry showed the rare remaining tumor cells to be Ki67 negative and p16 positive suggestive of cellular senescence. The study further performed spatial transcriptomic analysis on pairs of pre- and posttreatment tumor tissue to demonstrate activation of senescence pathway in SAbR treated primary RCC.6
Considering its precision, SAbR is not limited to the tumor location within the kidney and is therefore able to effectively treat endophytic tumors including those adjacent to the renal pelvis.6 In addition, retrospective studies have shown SAbR to be effective in ≥T1b renal tumors with LC rates >95%.5 With regards to the effect on renal function, a systematic review and meta-analysis of SAbR for primary RCC demonstrated a mean change in estimated glomerular filtration rate before and after SAbR of −7.7 mL/min.7 The majority of SAbR toxicities are mild, including nausea, fatigue, and dermatitis. The mean rate of possibly related grade 3-4 toxicities is 1.5% including pyelonephritis and gastric and duodenal ulcers.5,7
Given these results, the current guidelines from the European Society of Medical Oncology, European Association of Urology, and the National Comprehensive Cancer Network consider SAbR as an alternative treatment for patients with localized RCC who are unable to undergo surgery due to poor performance status or unsuitable clinical condition.8-10
We believe this emerging technique holds great promise, characterized by rapid evolution and encouraging outcomes. Our selected patient presented is currently 89 years old, doing well with no signs of progression up to 5 years after SAbR.
- Potters L, Kavanagh B, Galvin JM, et al. American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) practice guideline for the performance of stereotactic body radiation therapy. Int J Rad Oncol Biol Phys. 2010;76(2):326-332.
- Ponsky LE, Mahadevan A, Gill IS, Djemil T, Novick AC. Renal radiosurgery: initial clinical experience with histological evaluation. Surg Innov. 2007;14(4):265-269.
- Ponsky LE, Crownover RL, Rosen MJ, et al. Initial evaluation of cyberknife technology for extracorporeal renal tissue ablation. Urology. 2003;61(3):498-501.
- Siva S, Ali M, Correa RJ, et al. 5-Year outcomes after stereotactic ablative body radiotherapy for primary renal cell carcinoma: an individual patient data meta-analysis from IROCK (the international radiosurgery consortium of the kidney). Lancet Oncol. 2022;23(12):1508-1516.
- Ali M, Mooi J, Lawrentschuk N, et al. The role of stereotactic ablative body radiotherapy in renal cell carcinoma. Eur Urol. 2022;82(6):613-622.
- Hannan R, McLaughlin MF, Pop LM, et al. Phase 2 trial of stereotactic ablative radiotherapy for patients with primary renal cancer. Eur Urol. 2023;10.1016/j.eururo.2023.02.016.
- Correa RJ, Louie AV, Zaorsky NG, et al. The emerging role of stereotactic ablative radiotherapy for primary renal cell carcinoma: a systematic review and meta-analysis. Eur Urol Focus. 2019;5(6):958-969.
- Escudier B, Porta C, Schmidinger M, et al. Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(5):706-720.
- Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of Urology guidelines on renal cell carcinoma: the 2019 update. Eur Urol. 2019;75(5):799-810.
- National Comprehensive Cancer Network. Kidney Cancer, Version 2.2022. Accessed May 15, 2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf