Prostate cancer: Zapping metastatic tumors with radiation improves survival

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 degree — generally defined as no more than three to five areas outside the prostate gland, most commonly the lymph nodes or bones.

Barely a decade ago it was considered universally fatal, and treatment was limited to systemic hormonal therapies that shut down testosterone, a hormone that drives the tumors to grow. But now, exciting developments in the field are leading to new treatment strategies that are improving patient survival in clinical trials.

These strategies are enabled by advances in medical imaging, revealing metastatic tumors that were previously too small to see. Doctors can now treat the tumors directly with radiation or surgery. This is called metastasis-directed therapy (MDT), and it is allowing some men with oligometastatic prostate cancer to delay or even completely avoid hormonal therapy, along with its challenging side effects.

Now, results from an important new study show that beneficial responses to MDT hold up with long-term follow-up.

The researchers' methodology

To generate the findings, researchers combined results from two prior studies that randomized men to MDT or observation: one called STOMP and another 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 multiple directions, while sparing healthy tissues. Taken together, the studies showed that MDT delays cancer progression and the subsequent need for hormonal therapy. After they were published, MDT started becoming more widely adopted.

For this new study, the STOMP and ORIOLE subjects were combined into a single group of 116 men with a median follow-up of 52.5 months. The research's aim was to compare differences in progression-free survival (the amount of time it takes for the cancer to worsen) between men who were treated with MDT and those who were not.

Results showed a clear benefit from radiation: progression-free survival lasted 11.9 months, on average, among the MDT-treated men, compared to 5.9 months among the untreated controls.

But the researchers also went a step further: they analyzed archived samples of the subjects' blood and tumor tissues for cancer-associated mutations in five different genes: ATM, BRCA1, BRCA2, Rb1, and TP53. Again, the data revealed a stark discrepancy: among men with at least one mutation, progression-free survival lasted an average of 7.5 months, compared to 13.4 months on average among those who had none.

Remarkably, progression-free survival lasted four years or longer in up to 20% of the MDT-treated men, regardless of their mutational status. But in general, men lacking in the mutations had the best responses. MDT by itself may be initially sufficient for these men, the researchers concluded, while among those with high-risk mutations, MDT might be more effective if paired with a systemic therapy.

An expert's reaction

"The authors should be applauded for their respectable follow-up of 52 months," says Dr. Nima Aghdam, a radiation oncologist at Beth Israel Deaconess Medical Center in Boston, and a member of the Harvard Medical SchoolAnnual Report on Prostate Diseases advisory board. In the right setting, Dr. Aghdam added, MDT can be delivered safely, delaying treatments that often lead to 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 may be, Dr. Aghdam said, that MDT given by itself offers a pathway for a long-term, disease-free period 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 defer="defer" ADT for a long time will be broadly appreciated."