Patients with oligometastatic disease who received stereotactic ablative radiotherapy (SABR) had a significant threefold decrease in disease progression at 6 months compared with patients who were randomly assigned to observation alone.
“Local control for SABR-treated lesions was excellent, and the adverse effects associated with SABR were mild and did not appear to affect quality of life,” say the investigators, led by Ryan Phillips, MD, PhD, from the Johns Hopkins Sidney Kimmel Cancer Center in Baltimore.
“Although the approach is controversial, many men are interested in avoiding the unpleasant adverse effects and potential health risks of androgen deprivation therapy (ADT) for as long as is reasonable,” they write.
These results come from outcomes of the Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 trial and were published online March 26 in JAMA Oncology.
An intriguing finding from the study was evidence that SABR may evoke an immune response.
“We observed enhanced differential clonotype expansion, clusters of similar expanded T-cell receptors, and a clinical benefit to greater baseline clonality seen only in participants treated with SABR,” said senior author Phuoc T. Tran, MD, PhD, from the department of radiation oncology and molecular radiation sciences at Johns Hopkins.
“This the only data I’m aware of that really shows that radiation in isolation can cause a systemic immune response,” Tran told Medscape Medical News.
Previous studies suggesting an immune response with radiation have been confounded by coadministration of radiation and chemotherapy, he said.
Drive the Disease to ‘Near Extinction’
SABR appears to “alter the natural history of prostate oligometastatic disease by removing or greatly affecting signals that promote further development of micrometastatic disease,” write the authors of accompanying editorial.
This hypothesis is consistent with the oligometastatic paradigm, which postulates that this is a transient phase that offers “a window of opportunity for cancer cure if equilibrium-phase lesions are ablated before polymetastatic escape occurs,” write Carlo Greco, MD, and Zvi Fuks, MD, both from the Champalimaud Centre for the Unknown, Lisbon, Portugal; Fuks is also affiliated with Memorial Sloan Kettering Cancer Center, New York.
“Taken together, these observations support the hypothesis that all detectable oligometastatic lesions should be systematically ablated, if feasible, in an effort to maximize oligometastatic cancer cure,” Greco and Fuks comment.
However, there is no clear consensus on what constitutes oligometastatic disease, they point out, and they warn that “a numerical-based decision to withhold lesion ablation may represent a strategic error, potentially reducing the benefit of metastasis-directed therapy (MDT) in the treatment of oligometastatic cancer.”
“We speculate that, if clinically and technically feasible, there should be no restriction to MDT at first oligometastatic presentation and as sequential lesions appear, regardless of lesion numbers, because each lesion may potentially constitute a generator of evolving metastatogenic clonogens,” they add.
Multiple rounds of MDT theoretically could “drive the disease to near extinction” and prevent the development of polymetastatic disease, they contend.