Treatment of Oligometastatic Bladder Cancer with SBRT - Expert Commentary
Between 2011 and 2018, data from 82 lesions in 61 patients were analyzed across three institutions. The median patient age was 71 years (range 48.2-86.2), 83.6% were male. Primary tumors were located in the bladder (82%), renal pelvis (11.5%), ureter (4.9%), and urethra (1.6%). The median disease-free interval was 14.5 months (range 0-121.8). The most commonly treated metastatic sites were lung (40.2%) and lymph nodes (35.4%). Single metastasis treatment occurred in 37 patients (60.7%), while 39.3% received treatment for two to five metastases simultaneously. Prior systemic therapy was administered to 29 patients (47.5%), and 14 patients (23%) received concurrent systemic therapy during SBRT.
Treatment was delivered using either linear accelerator-based SBRT (81.7%) or robotic arm-based systems (18.3%). The median delivered dose was 45 Gy (range 18-70) administered in one to ten fractions, with a median BED10 value of 78.7 Gy (range 37.5-151.2). The most common fractionation schedule was 48 Gy in four fractions (23.2%), followed by 45 Gy in six fractions (15.9%).
With a median follow-up of 17.2 months (range 3-91), excellent local control was achieved. Local control rates at one and two years were 92% (95% confidence interval 90.4-99.8) and 88.9% (95% confidence interval 76.1-95.1), respectively. Univariate analysis revealed that prior lines of systemic therapy before SBRT were associated with inferior local control (hazard ratio 2.62, P = 0.034). Distant progression-free survival at one and two years was 49.6% and 42.5%, respectively, with a median of 10.1 months. The presence of more than one metastasis was associated with inferior distant progression-free survival (hazard ratio 2.10, P = 0.041). Overall progression-free survival rates at one and two years were 47.9% and 38.1%, respectively, with a median of 10.1 months. Multiple metastases remained a negative predictive factor for overall progression-free survival (hazard ratio 2.65, P = 0.008).
The median overall survival was 25.6 months, with one- and two-year survival rates of 78.9% and 50.7%, respectively. On univariate analysis, both total delivered dose (hazard ratio 0.93, P = 0.003) and BED10 (hazard ratio 0.97, P = 0.006) were significantly correlated with improved overall survival. During follow-up, six lesions (7.3%) experienced in-field progression, while 34 patients (55.7%) developed new metastases. At last follow-up, 49 patients (80.3%) remained alive. Safety analysis demonstrated excellent tolerability with minimal toxicity. Four patients reported grade 1 acute side effects, including fatigue, pain, and nausea. Two cases each of grade 1 pneumonitis, skin erythema, and late fibrosis were observed. Notably, no grade 2 or higher adverse events were reported in this cohort, even among the 23% of patients who received concurrent systemic therapy.
Limitations of the study include its retrospective design, heterogeneous patient population, and potential underestimation of toxicity. However, these findings suggest that SBRT represents an effective and safe treatment modality for oligometastatic urothelial carcinoma. The excellent local control rates, favorable survival outcomes, and minimal toxicity profile support SBRT as a viable alternative to surgical metastasectomy, particularly in patients deemed inoperable due to comorbidities or anatomical constraints. As the authors concluded, prospective randomized trials are necessary to better evaluate the potential benefit of SBRT in delaying the onset of new systemic therapies and to investigate optimal patient selection criteria for this ablative approach, especially in the era of first-line treatment with Enfortumab Vedotin and Pembrolizumab.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
References:
Read the Abstract