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Prostate RT Ups Overall Survival in Metastatic Disease

— Benefit limited to men with low disease burden

Ƶ MedicalToday

MUNICH -- Men with newly diagnosed metastatic prostate cancer and a low disease burden lived significantly longer when they received radiotherapy to the prostate, according to a new analysis of a large randomized trial.

Patients with low metastatic burden had a 3-year overall survival of 81% when receiving radiation therapy in addition to standard care. That compared with a 3-year overall survival of 73% in men treated with standard care alone (primarily androgen deprivation therapy, ADT).

In men with a high metastatic disease burden, however, radiation to the prostate did not improve survival, researchers reported here at the annual congress.

"On the basis of these results, we believe that prostate radiotherapy should be a standard treatment option for men with a low metastatic burden," said Chris Parker, MD, of the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust in Sutton, England.

The findings have implications that go beyond the management of men with distant metastases and relate to men with lymph node metastases, who were not included in the trial, Parker said.

"If prostate radiotherapy improves survival for men with distant metastases, we can be very confident that it would improve survival for men with regional nodal disease," said Parker. "There aren't any trials addressing that question, and currently, many of these men receive drug treatment alone. Going forward, prostate radiotherapy should be a standard treatment for these men as well."

The results were published simultaneously in .

Although the trial failed to meet the primary endpoint -- survival in the overall study population, other urologic oncologists agreed that the benefit observed in men with low disease burden will change clinical practice.

"We were mentally used to handling these patients in a different way and that was cutting down the main fuel for prostate cancer, which is testosterone," said Ignacio Duran, MD, of Hospital Universitario Marques de Valdecilla in Santander, Spain. "We had never considered treating the local tumor in the context of widespread disease. This is what I think is revolutionary about this study."

Karim Fizazi, MD, of Gustave Roussy Institute in Villejuif, France, said, "For men with newly diagnosed oligometastatic prostate cancer, it is quite likely that this data is practice changing. For men with higher burden of disease, more data are needed regarding whether upfront local treatment improves or prevents local symptoms, which, by itself, may justify its use in the absence of an overall survival benefit."

The findings came from the long-running STAMPEDE trial, a multiarm, multistage clinical investigation designed to evaluate different treatments for prostate cancer in sequential order. Previous studies confirmed the benefits of adding to ADT or abiraterone (Zytiga) to ADT for men with metastatic hormone-sensitive prostate cancer, the same type of patients enrolled in the radiotherapy trial.

The rationale for evaluating prostate radiotherapy in newly diagnosed metastatic prostate cancer included several retrospective analyses that showed improved survival in men who received radiotherapy to the primary tumor. The benefits appeared greater in men who had a good prognosis, said Parker.

Subsequently the randomized evaluated the addition of prostate radiotherapy to ADT in men with newly diagnosed metastatic disease and showed no survival benefit. However, the trial demonstrated a nonsignificant 32% reduction in the hazard ratio among men with fewer than five bone metastases.

Investigators in the STAMPEDE trial hypothesized that radiotherapy to the prostate, in addition to ADT, would improve overall survival as compared with ADT alone. After the trial began, an accumulation of data outside the trial led them to prespecify that any benefit from radiotherapy would be greater in men low metastatic disease burden (as defined in the ). The protocol also was amended to allow use of docetaxel as part of standard care after the drug was approved for the indication in England.

Investigators randomized 2,061 patients to the two treatment arms. External-beam radiation therapy (EBRT) was administered on a daily schedule over 4 weeks or weekly for 6 weeks. The primary data analysis occurred after a median follow-up of 37 months and showed a 3-year survival of 62% in the control group and 65% in the radiotherapy group (HR 0.92, 95% CI 0.80-1.06, P=0.266).

The prespecified analysis of survival by disease burden yielded a statistically significant 32% reduction in the hazard ratio in favor of the radiotherapy arm (95% CI 0.52-0.90, P=0.007). The addition of radiotherapy to standard care did not improve 3-year survival in men with a high metastatic burden at diagnosis (53% versus 54%, HR 1.07, 95% CI 0.90-1.28, P=0.420).

Parker said adverse effects in the radiotherapy group were manageable and consistent with the know effects of EBRT, as 48 patients reported one or more grade 3/4 adverse events. Overall, adverse event rates were similar between the treatment groups and dominated by side effects of ADT.

"We've proven the principle in prostate cancer, that treating the primary tumor can improve survival in men with metastatic disease," said Parker. "This concept should now be tested in patients with oligometastastic disease, low burden metastatic disease, from other malignancies."

  • author['full_name']

    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined Ƶ in 2007.

Disclosures

The study was sponsored by the Medical Research Council of England.

Parker reported relationships with Bayer, Janssen, and Advanced Accelerator Applications.

Primary Source

European Society for Medical Oncology

Parker CC, et al “Radiotherapy (RT) to the primary tumor for men with newly diagnosed metastatic prostate cancer (PCa): Survival results from STAMPEDE (NCT00268476)” ESMO 2018; Abstract LBA5_PR.

Secondary Source

The Lancet

Parker CC, et al "Radiotherapy to the primary tumor for newly diagnosed metastatic prostate cancer (STAMPEDE): A randomized controlled phase III trial" Lancet 2018; doi: 10.1016/S014-6736(18)32486-3.