Prostate cancer: Radiating metastatic tumors improves survival

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

Nearly a decade ago, it was considered universally fatal, and treatment was limited to systemic hormonal therapies that shut down testosterone, a hormone that drives 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 made possible by advances in medical imaging that reveal 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 allows some men with oligometastatic prostate cancer to delay or even avoid hormone therapy entirely, along with its challenging side effects.

Now the results of an important new study show that positive responses to MDT persist even with long-term follow-up.

The researchers' methodology

To generate the results, researchers combined results from two previous 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 radiation therapy, which focuses intense beams of radiation from multiple directions on tumors while sparing healthy tissue. Taken together, the studies showed that MDT delayed cancer progression and the subsequent need for hormone therapy. After its release, MDT began to become more and more popular.

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 aim of the research was to compare the differences in progression-free survival (the amount of time it takes 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 in the men treated with MDT, compared to 5.9 months in the untreated controls.

But the researchers went one step further: They analyzed archived blood and tumor tissue samples from the subjects for cancer-associated mutations in five different genes: ATM, BRCA1, BRCA2, Rb1 and TP53. Here too, the data showed a stark discrepancy: progression-free survival lasted an average of 7.5 months in men with at least one mutation, compared to an average of 13.4 months in men without a mutation.

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

An expert's reaction

“The authors should be applauded for their respectable 52-month follow-up,” says Dr. Nima Aghdam, a radiation oncologist at Beth Israel Deaconess Medical Center in Boston and a member of theHarvard Medical SchoolAnnual report on prostate diseasesAdvisory Board. In the right environment, added Dr. Adding Aghdam, MDT can be administered safely, delaying treatments that often result in impaired patient quality of life.

Selecting the right patients for treatment is crucial, but the mutations identified "may allow us in the future to determine who will benefit most from MDT," he said. It may be, said Dr. Aghdam said MDT administered alone provides a route to long-term, disease-free periods in patients treated in outpatient settings. "This will require longer studies to clarify," he said, "but the possibility that a good proportion of patients may delay ADT for a long time is widely recognized."