Is there any benefit to early treatment of asymptomatic men with many bone metastases? We saw that, at least in a retrospective study, there was no oncological benefit to treatment of oligo (1-5) bone metastases. But even if there is no benefit in delaying cancer progression, perhaps spinal radiation can prevent pain and crippling spinal compression?
Dearnaly et al. reported the results of a large multicenter randomized trial in the UK among 420 men with castration-resistant prostate cancer with asymptomatic spinal metastases on a bone scan. The goal was to determine whether early detection with MRI and treatment (SBRT radiation) could prevent clinical spinal cord compression (cSCC).
- The MRI detected early signs of spinal cord compression in 31% (61 patients), and they were treated with SBRT radiation using 20 Gy in 5 treatments.
The 1-yr and 2-yr results for all 210 men given MRIs (the "intervention group"), whether SCC was detected radiographically or not:
- At 12 months after randomization, the incidence of cSCC was 4.3% for the intervention group and 6.7% for the control group (no statistically significant difference)
- At 24 months after randomization, the incidence of cSCC was 9.2% for the intervention group and 12.6% for the control group (no statistically significant difference)
- Pain scores and severity of SCC were similar in both groups.
- Chemotherapy was more often used in the control group.
- Prostate cancer-specific mortality was similar in both groups.
- Overall survival was the same (22 months) in both groups. Note: this was a very progressed population of patients
- At 12 months after randomization, the incidence of cSCC was 11.5% for the MRI+ group and 1.3% for the MRI- group (note: statistically significant difference even after treatment)
- At 24 months after randomization, the incidence of cSCC was 13.2% for the MRI+ group and 7.6% for the MRI- group (note: statistically significant difference even after treatment)
- MRI+ patients had more clinical SCC, regardless of early detection and therapy.
So, there was no benefit to early detection and treatment. Perhaps there is a sub-group that could benefit?
Gillespie et al. reported the results of a small multicenter randomized trial among 78 men and women (22% had prostate cancer) who had more than 5 metastatic lesions identified on a bone scan, where none were yet painful ("asymptomatic"), but at least one of the bone metastases was "high risk." High risk was defined as any of:
- 2 cm or more in diameter
- at a junction in the spine between the cervix, thorax, lumbar, and sacral vertebrae
- in the hip or sacroiliac joint
- in a long bone (arms or legs) (note: this is rare for prostate cancer)
Patients were randomly treated with non-ablative radiation. After at least 1 year of follow-up, they observed the rate of skeletal-related events (SREs) and mortality. SREs could be pain, spinal compression, or fractures:
- SREs occurred in 1.4% of those receiving radiation vs 29% of those receiving standard care
- After 3 months, but not afterward, there was less pain reported by those who received radiation.
- There were no quality of life differences at any point in time.
After a median of 2.4 years of follow-up:
- Survival was 1.5 years for those with no SRE vs 1.1 year for those with an SRE
A single ablative dose for painful non-spinal metastases has been found to be superior in this study. Fewer higher doses (24 Gy in 2 treatments) were more effective than 20 Gy in 5 treatments for relieving pain from spinal metastases in this study. Sahgal et al. in a Canadian/Australian multi-institutional trial, found there was a better pain response with SBRT (24 Gy in 2 fractions) compared to IMRT (20 Gy in 5 fractions). After 3 months, significant pain improvement was 35% for SBRT vs 14% for IMRT.
There is similar data from Heidelberg. Sprave et al. reported better pain response at 6 months (but not at 3 months) with SBRT (24 Gy in 1 fraction) vs 3DCRT (30 Gy in 10 fractions).
Conflictingly, Ryu et al. reported the results of the NRG Oncology/RTOG 0631 randomized clinical trial. They tried to obtain proof that SBRT (16-18 Gy in one dose) was superior to IMRT in one dose (8 Gy) in terms of pain response. After 3 months, 61% of those treated with IMRT had a significant pain improvement vs 41% of those treated with SBRT. After 1 year, there was no difference in pain scores. After 2 years, there was no difference in spinal fractures or compression.
Spinal dosimetry depends on extent and soft-tissue involvement, and may require a neurological consult.