For some men, this strategy eliminates the need for hormone therapy.
Oligometastatic cancer is an early form of stage 4 prostate cancer that has spread to other organs in the body, but only to a limited extent – usually defined as no more than three to five areas outside the prostate gland, most commonly lymph nodes or the bones.
Only a decade ago it was considered universally fatal and treatment was limited to systemic hormone therapies that stop testosterone, a hormone that makes tumors grow. But now exciting developments in the field are leading to new treatment strategies that are improving patient survival in clinical trials.
These strategies have been enabled by advances in medical imaging, revealing metastatic tumors that were previously too small to see. Doctors can now treat tumors directly with radiation or surgery. This is called metastasis-directed therapy (MDT), and it allows some men with oligometastatic prostate cancer to delay or even completely avoid hormone therapy, along with its challenging side effects.
Now, the results of an important new study show that beneficial responses to MDT are maintained at long-term follow-up.
The methodology of the researchers
To generate the findings, the researchers combined results from two previous studies that randomized men to MDT or observation: one called STOMP and the other called ORIOLE. The men in the studies were treated with a technique called stereotactic ablative radiotherapy, which focuses intense beams of radiation on tumors from different directions while sparing healthy tissue. Taken together, the studies show that MDT delays cancer progression and the subsequent need for hormone therapy. After they were published, MDTs began to be more widely adopted.
For this new study, STOMP and ORIOLE subjects were combined into one group of 116 men with a mean follow-up of 52.5 months. The aim of the study was to compare the differences in progression-free survival (the time it took for the cancer to get worse) between men who were treated with MDT and those who were not.
The results showed a clear benefit of radiation: progression-free survival lasted an average of 11.9 months among men treated with MDT, compared with 5.9 months among untreated controls.
But the researchers went a step further: They analyzed archived samples of the subjects’ blood and tumor tissues for cancer-related mutations in five different genes: ATM, BRCA1, BRCA2, Rb1 and TP53. Again, the data revealed a stark disparity: Among men with at least one mutation, progression-free survival lasted an average of 7.5 months, compared to an average of 13.4 months among those without one.
Remarkably, progression-free survival lasted four years or longer in up to 20% of men treated with MDT, regardless of their mutational status. But overall, men without mutations had the best responses. MDT alone may be sufficient initially for these men, the researchers concluded, while among those with high-risk mutations, MDT may be more effective if combined with systemic therapy.
“The authors should be applauded for their respectable follow-up of 52 months,” said Dr. Nima Aghdam, a radiation oncologist at Beth Israel Deaconess Medical Center in Boston and a member of Harvard Medical SchoolAnnual Report on Diseases of the Prostate Advisory Board. In the right setting, Dr. Aghdam added, MDT can be delivered safely, delaying treatment that often results in a decline in the patient’s quality of life.
Selecting the right patients for treatment is critical, but the mutations identified “may allow us in the future to determine who will benefit most from MDT,” he said. It’s possible, Dr. Aghdam said, that MDT given alone could offer a pathway to long-term disease-free periods among patients treated in community settings. “This will require longer studies to clarify,” he said, “but the possibility that a good proportion of patients can delay = ‘put off’ ADT for a long time will be widely appreciated.”