San Francisco, CA (UroToday.com) The treatment selection for localized renal tumors session at GU ASCO 2020 featured Shankar Siva, PhD, MBBS, who discussed the role of stereotactic radiation for the treatment of small renal masses. Dr. Siva highlights that there are several nephron sparing options for primary rencal cell carcinoma (RCC), including partial nephrectomy (the best options for peri-hilar or larger tumors), cryoablation and radiofrequency ablation (avoids a general anesthetic), as well as SABR – which also avoids a general anesthetic, is non-invasive and may be feasible for complex anatomy tumors.
Despite our possible preconceived notions, according to Dr. Siva, RCC is not radioresistant to ablative therapy. A meta-analysis of 28 studies published last year showed that 1,602 mutually exclusive patients were treated with SABR for oligometastatic RCC, including 679 extracranial and 923 intracranial lesions. The timeline for SABR for primary RCC dates back to 1953, however has become more mainstream over the past 5-10 years. Dr. Siva states that the rationale for using SABR in primary RCC is that not all RCCs are the same in that (i) the primary RCC may not be suitable for surgery, (ii) the tumor is in a solitary kidney, or (iii) there is a failure after thermal ablation.
Dr. Siva was the lead author of the FASTRACK (Focal Ablative Stereotactic Radiosurgery for Cancers of the Kidney) prospective clinical trial that was published in 2017.2 There were 37 inoperable patients enrolled with a median age of 78 years, 62% of which had T1b tumors, 35% had T1a and 3% had T2a disease, and histology was confirmed in 92% of patients. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). Over a median follow-up of 24 months, the 2-year freedom from local progression rate was 100%, freedom from distant progression rate was 89% and overall survival rate was 92%. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (p < 0.001).
In 2016, the International Radiosurgery Oncology Consortium for Kidney (IROCK) group released a consensus statement regarding the treatment of primary renal cell carcinoma.3 For this statement, eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. All centers treat patients with pre-existing hypertension and solitary kidneys, five institutions apply size constraints of 5-8 cm, and the total planning target volume expansion is 3-10 mm. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes CT (n = 8), PET-CT (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years.
The IROCK group published their multicenter pooled analysis of SABR in 2018, an analysis that comprised 223 patients.4 There were 118 patients that received single-fraction SABR, and 105 that received multi-fraction SABR. The mean patient age was 72 years, and 69.5% of patients were male. There were 83 patients with grade 1 and 2 toxicity (35.6%) and 3 (1.3%) with grade 3 and 4 toxicities. The 2-year rate of local control was 97.8%, for cancer-specific survival was 95.7%, and for progression-free survival 77.4%. At 4-years, the rate of local control was 97.8%, cancer-specific survival was 91.9%, and progression free survival was 65.4%. On multivariable analysis, tumors with a larger maximum dimension (HR 1.16, p < 0.01) and the receipt of multi-fraction SABR (HR 1.13, p = 0.02) were associated with poorer progression-free survival, and poorer cancer-specific survival (HR 1.28, p < 0.01 for tumor dimension and HR 1.33, p = 0.01 for multi-fraction SABR).
The IROCK group has also recently published their experience with SABR among patients with solitary kidneys.5 In this study, 81 patients with a solitary kidney underwent stereotactic ablative radiotherapy. The mean age was 67.3 years and 97.5% of patients had good performance status, including ECOG 0-1 or Karnofsky Performance Status 70% or greater. Median tumor diameter was 3.7 cm (IQR 2.5-4.3) and 37% of tumors were 4 cm or greater. The patients with solitary kidneys were compared to 138 patients with bilateral tumors. These patients had larger tumors and were older (p <0.001), with a lower baseline eGFR (p = 0.024) compared to those with solitary kidneys. After SABR in the solitary kidney cohort the mean ± SD estimated glomerular filtration rate decrease was -5.8 ± 10.8 ml per minute (-9%). Impressively, no patient with a solitary kidney required dialysis. After SABR, a tumor size of ≥4 cm was associated with an eGFR decrease of 15 ml per minute or greater (OR 4.2, p = 0.029). At 2 years in the solitary cohort the rate of local control was 98.0%, of progression-free survival was 77.5%, of cancer specific survival was 98.2%, and of overall survival 81.5%.
A recent systematic review and meta-analysis published in European Urology Focus summarizes the currently landscape of SABR for the treatment of primary RCC.6 From 1995-2019, the authors identified 2,386 PubMed entries and 924 meeting abstracts, of which 26 studies were identified (11 prospective trials), including 383 tumors in 372 patients, most of whom were deemed inoperable. Weighted averages of median follow-up was 28.0 (range 5.8-79.2) months, median age was 70.4 (range 62-83) years, and mean tumor size was 4.6 (range 2.3-9.5) cm. RCC histology was confirmed in 78.9% of patients who underwent pretreatment biopsy. Dose fractionation varied, but 26Gy in one fraction and 40Gy in five fractions were most commonly used. The random-effect estimate for local control was 97.2% (95% CI 93.9-99.5%, I2=20%), grade 3-4 toxicity was 1.5% (95% CI 0-4.3%, I2=0%), and post-SABR eGFR change -7.7ml/min (95% CI -12.5 to -2.8, I2=2%).
Future directions for SABR for the primary treatment of RCC include the FASTRACK phase II study, which will be a multicenter trial to validate efficacy. The sample size will be 70 patients with similar methodology to the FASTRACK pilot study. Knowledge based planning, functional mpMRI and SPECT imaging will be supported by a collaborative grant.
Dr. Siva concluded this talk on SABR by highlighting current limitations of using SABR for primary RCC:
- Tumors >10 cm
- Tumors in broad contact with the bowel
- RCC in a transplant kidney
- The lower limit of eGFR – Dr. Siva’s limit is <30 ml/min
Presented by: Shankar Siva, PhD, MBBS, Peter MacCallum Cancer Centre, Melbourne, Australia
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md, at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California.
References:
- Zaorsky NG, Lehrer EJ, Kothari G, et al. 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.
- Siva S, Pham D, Kron T, et al. Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: A prospective clinical trial. BJU Int 2017 Nov;120(5):623-630.
- Siva S, Ellis RJ, Ponsky L, et al. Consensus statement from the International Radiosurgery Oncology Consortium for Kidney for primary renal cell carcinoma. Future Oncol 2016 Mar;12(5):637-645.
- Siva S, Louie AV, Warner A, et al. Pooled analysis of stereotactic ablative radiotherapy for primary renal cell carcinoma: A report from the International Radiosurgery Oncology Consortium for Kidney (IROCK). Cancer 2018 Mar 1;124(5):934-942.
- Correa RJM, Louie AV, Staehler M, et al. Stereotactic Radiotherapy as a Treatment Option for Renal Tumors in the Solitary Kidney: A Multicenter Analysis from IROCK. J Urol 2019 Jun;201(6):1097-1104.
- Correa RJM, 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 Nov;5(6):958-969.