Stereotactic Ablative Radiation Therapy for Oligoprogressive Renal Cell Carcinoma

Abstract

Purpose: Oligoprogression, defined as limited sites of progression on systemic therapy, in patients with metastatic renal cell carcinoma (mRCC) is not uncommon, possibly because of inter-and intratumoral heterogeneity. We evaluated the effect of stereotactic ablative radiation therapy (SAbR) for longitudinal control of oligoprogressive mRCC. Methods and Materials: Patients with extracranial mRCC were included in this retrospective analysis if they progressed in ≤3 sites on systemic therapy while demonstrating response/stability at other sites and received SAbR to all progressing sites without switching systemic therapy. Our primary endpoint was modified progression-free survival (mPFS), which we calculated from the start of SAbR to the start of a subsequent systemic therapy, death, or loss to follow-up. Results: We identified 36 patients with a median follow-up of 20.4 months (interquartile range, 10.9-29.4). Forty-three sites were treated with SAbR with a median dose of 36 Gy (range, 18-50) in 3 fractions (range, 1-5). Median time to SAbR from the start of systemic therapy was 11.4 months (interquartile range, 6.1-17.1). Median mPFS was 9.2 months (95% confidence interval [CI], 5.9-13.2). Patients receiving SAbR while on immunotherapy exhibited a longer median mPFS (>28.4 months, log-rank P = .0001) than patients not on immunotherapy (9.2 months). Median overall survival from SAbR administration was 43.4 months (95% CI, 21.5-not Reached). The 1-year local control rate was 93% (95% CI, 78.7-97.5). Most SAbR-related toxicities were grade 1 to 2 (33% of patients), with one grade 5 hemoptysis event possibly related to SAbR or disease progression. Conclusions: SAbR has the potential to extend the the duration of current systemic therapy for selected patients with mRCC, preserving subsequent therapies for later administration possibly enabling longer treatment duration.

The Emerging Role of Extracranial Stereotactic Ablative Radiotherapy for Metastatic Renal Cell Carcinoma: A Systematic Review

“…Schoenhals et al [40] showed that conducting SABR during ICI treatment was associated with longer PFS (>28.4 mo, p = 0.0001), although these data have not been confirmed prospectively [41]. Further data on combined SABR and ICI therapies will be provided by the NCT04974671 singlearm phase II trial, currently opened but not yet recruiting.…”

“…2). The first report on SABR for patients with oligoprogressive mRCC showed an extended duration of the systemic therapy of approximately 9 mo [29,40]. Meyer et al [29] published the largest cohort of oligoprogressive mRCC patients, with a sample size of 101 patients.…”

“…As this retrospective study represents the first proof of concept for SABR in this setting, one of its major limitations relates to its conduct in the TKI era. More recently, Schoenhals et al [40] reported outcome results of 36 oligoprogressive patients diagnosed with favorable-risk (27.8%) or intermediate-risk (61.1%) IMDC mRCC. Of the patients, 91% received nephrectomy, performed either in nonmetastatic (75%) or in metastatic (16%) situations.…”

Current Options for Second-Line Systemic Therapy in Metastatic Renal Cell Carcinoma

“…Complete SBR (as opposed to incomplete SBR) may lead to improved cancer-specific survival in younger patients (age <55 years), with clear-cell tumors and low metastatic of <3 lesions (81). Another outcome often underscored in various studies is time to next systemic therapy initiation or time to systemic therapy escalation, which can be significantly prolonged with SBR for over a year, as well as with classic external beam radiation (82)(83)(84)(85)(86)(87)(88). Alternatively, SBR can significantly extend the duration of ongoing systemic therapy by more than 6 months without compromising the quality of life (89).…”

Stereotactic body radiation therapy for spine and non-spine bone metastases. GETUG (french society of urological radiation oncologists) recommendations using a national two-round modified Delphi survey

“…6,7 SBRT is often proposed to target oligometastases in the field of castration-sensitive prostate cancer or to treat metastases from renal cell carcinoma in order to postpone initiation or change of systemic therapies. 3,4,8 By inducing presentation of cancer antigens to the immune system, SBRT is also believed to stimulate a tumor-targeted immune response (bystander and abscopal effects) and to improve the therapeutic efficiency of immunotherapies (STAR effect). [9][10][11] In addition, a new era of therapeutic indications proposes the use of SBRT for pain relief for multimetastatic patients, as opposed to standard palliative irradiation.…”