Meeting NewsPerspective

Local radiotherapy extends survival for certain men with metastatic prostate cancer

MUNICH — Radiotherapy to the prostate did not prolong survival for unselected men with newly diagnosed metastatic prostate cancer, according to results from the STAMPEDE trial presented at European Society for Medical Oncology Congress.

However, results of a preplanned analysis showed men with a lower metastatic burden derived a survival benefit from this approach.

“Until now, men with metastatic prostate cancer have always been treated with drugs,” study author Chris Parker, BA, BM, BChir, MD, FRCR, MRCP, clinical oncologist with The Royal Marsden NHS Foundation Trust in the United Kingdom, said during a press conference. “It was thought that, if the cancer had spread elsewhere, there was no point in treating the prostate itself with surgery or radiotherapy because it was just too late.”

However, animal models of metastatic cancer showed treating the primary tumor slowed metastases and prolonged survival.

“We wanted to ask the question: Is the same thing was true of men with prostate cancer in the clinic,” Parker said. “We hypothesized that, if there was a benefit to treating the prostate, it was likely to be greater among men who had a low metastatic burden rather than many metastases.”

The STAMPEDE trial — a multiarm, multistage protocol — included a randomized phase 3 comparison to evaluate this hypothesis.

The analysis included 2,061 men with newly diagnosed metastatic prostate cancer were assigned between January 2013 and September 2016 to standard drug treatment — consisting of lifelong androgen deprivation therapy plus early docetaxel from 2016 — with or without prostate radiotherapy.

Radiotherapy, which started 8 weeks or less after randomization or docetaxel, was administered in one of two schedules: 55 Gy in 20 fractions over 4 weeks, or 36 Gy in six fractions over 6 weeks.

Both groups were balanced with regard to age (median, 68 years), PSA (median, 97 ng/mL), receipt of early docetaxel (18%) and metastatic burden (40% lower, 54% higher, 6% not known).

Death from any cause served as the primary outcome measure. Secondary outcomes included failure-free survival, and a prespecified subgroup analysis assessed effects by metastatic burden at study entry.

In the overall study population, prostate radiotherapy extended failure-free survival (HR = 0.76; 95% CI, 0.68-0.84) but not OS (HR = 0.92; 95% CI, 0.8-1.06).

When researchers assessed local radiotherapy’s effect based on metastatic burden, results showed a significant OS benefit for the 819 men with lower metastatic burden (HR = 0.68; 95% CI, 0.52-0.9), defined as disease spread to nearby bones or lymph glands.

Three-year OS rates among men with low metastatic burden were 81% for those who received radiotherapy and 73% for those who did not.

The 1,120 men with high metastatic burden — defined as disease spread to distant bones or other organs, such as the liver — did not derive an OS benefit from radiotherapy (HR = 1.07; 95% CI, 0.9-1.28).

The experimental regimen appeared well tolerated. Rates of grade 3 or grade 4 adverse events among men who received radiotherapy were 5% during treatment and 4% after treatment.

“Going forward, prostate radiotherapy should now be a standard treatment option for men with newly diagnosed metastatic prostate cancer with a low metastatic burden,” Parker said.

The findings also have implications for men with regional nodal metastases but not metastatic disease, he added.

“These men were not included in our trial. However, if prostate radiotherapy improves survival for men with distant metastases, we could be very confident it would improve survival for men with regional nodal disease,” Parker said.

No trials are underway to address that question, and many of these men receive drug treatment alone. Going forward, prostate radiotherapy should be a standard treatment for these men, as well, Parker said.

“Lastly, we have proven the principle in prostate cancer that treating the primary tumor can improve survival among men with metastatic disease, so this concept should now be tested in patients with low-burden oligometastatic disease from other malignancies,” Parker said. – Mark Leiser

Reference:

Parker CC, et al. Abstract LBA5_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosures: Cancer Research UK provided funding for this trial. Parker reports research funding from Bayer, as well as personal fees from Advanced Accelerator Applications, Bayer and Janssen. Please see the abstract for all other authors’ relevant financial disclosures.

MUNICH — Radiotherapy to the prostate did not prolong survival for unselected men with newly diagnosed metastatic prostate cancer, according to results from the STAMPEDE trial presented at European Society for Medical Oncology Congress.

However, results of a preplanned analysis showed men with a lower metastatic burden derived a survival benefit from this approach.

“Until now, men with metastatic prostate cancer have always been treated with drugs,” study author Chris Parker, BA, BM, BChir, MD, FRCR, MRCP, clinical oncologist with The Royal Marsden NHS Foundation Trust in the United Kingdom, said during a press conference. “It was thought that, if the cancer had spread elsewhere, there was no point in treating the prostate itself with surgery or radiotherapy because it was just too late.”

However, animal models of metastatic cancer showed treating the primary tumor slowed metastases and prolonged survival.

“We wanted to ask the question: Is the same thing was true of men with prostate cancer in the clinic,” Parker said. “We hypothesized that, if there was a benefit to treating the prostate, it was likely to be greater among men who had a low metastatic burden rather than many metastases.”

The STAMPEDE trial — a multiarm, multistage protocol — included a randomized phase 3 comparison to evaluate this hypothesis.

The analysis included 2,061 men with newly diagnosed metastatic prostate cancer were assigned between January 2013 and September 2016 to standard drug treatment — consisting of lifelong androgen deprivation therapy plus early docetaxel from 2016 — with or without prostate radiotherapy.

Radiotherapy, which started 8 weeks or less after randomization or docetaxel, was administered in one of two schedules: 55 Gy in 20 fractions over 4 weeks, or 36 Gy in six fractions over 6 weeks.

Both groups were balanced with regard to age (median, 68 years), PSA (median, 97 ng/mL), receipt of early docetaxel (18%) and metastatic burden (40% lower, 54% higher, 6% not known).

Death from any cause served as the primary outcome measure. Secondary outcomes included failure-free survival, and a prespecified subgroup analysis assessed effects by metastatic burden at study entry.

In the overall study population, prostate radiotherapy extended failure-free survival (HR = 0.76; 95% CI, 0.68-0.84) but not OS (HR = 0.92; 95% CI, 0.8-1.06).

When researchers assessed local radiotherapy’s effect based on metastatic burden, results showed a significant OS benefit for the 819 men with lower metastatic burden (HR = 0.68; 95% CI, 0.52-0.9), defined as disease spread to nearby bones or lymph glands.

PAGE BREAK

Three-year OS rates among men with low metastatic burden were 81% for those who received radiotherapy and 73% for those who did not.

The 1,120 men with high metastatic burden — defined as disease spread to distant bones or other organs, such as the liver — did not derive an OS benefit from radiotherapy (HR = 1.07; 95% CI, 0.9-1.28).

The experimental regimen appeared well tolerated. Rates of grade 3 or grade 4 adverse events among men who received radiotherapy were 5% during treatment and 4% after treatment.

“Going forward, prostate radiotherapy should now be a standard treatment option for men with newly diagnosed metastatic prostate cancer with a low metastatic burden,” Parker said.

The findings also have implications for men with regional nodal metastases but not metastatic disease, he added.

“These men were not included in our trial. However, if prostate radiotherapy improves survival for men with distant metastases, we could be very confident it would improve survival for men with regional nodal disease,” Parker said.

No trials are underway to address that question, and many of these men receive drug treatment alone. Going forward, prostate radiotherapy should be a standard treatment for these men, as well, Parker said.

“Lastly, we have proven the principle in prostate cancer that treating the primary tumor can improve survival among men with metastatic disease, so this concept should now be tested in patients with low-burden oligometastatic disease from other malignancies,” Parker said. – Mark Leiser

Reference:

Parker CC, et al. Abstract LBA5_PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosures: Cancer Research UK provided funding for this trial. Parker reports research funding from Bayer, as well as personal fees from Advanced Accelerator Applications, Bayer and Janssen. Please see the abstract for all other authors’ relevant financial disclosures.

    Perspective

    There are approximately 1.2 million new cases of prostate cancer worldwide every year, so it is a huge health problem. Most cases, at least in the Western world, are diagnosed as localized disease. These patients are treated with either surgery or radiation. A certain percentage of these men will relapse with advanced disease that becomes metastatic.

    The study that Dr. Parker presented applies to patients who initially present with metastatic disease. This accounts for only about 10% of cases in the Western world, but that is still a relevant number of men.

    We have become accustomed to handling these patients in a different way, using androgen blockade to cut down the main fuel for prostate cancer, which is testosterone. More recently, we added new treatments to that, such as docetaxel or abiraterone acetate (Zytiga, Janssen), but we have never considered treating the local tumor in a context of widespread disease.

    Researchers in the STAMPEDE trial have answered the question about the impact of treating the prostate when the disease is already widespread. This is revolutionary. The benefit does not apply to all patients with prostate cancer, but there is a substantial group that still might benefit.

    There are questions that still must be answered. When this study was designed, we were not using drugs that have since been incorporated into this setting. For example, what is the role of docetaxel or abiraterone in combination with radiation? Still, I think these data are quite provocative.

    • Ignacio Duran, MD, PhD
    • Hospital Universitario Marques de ValdecillaSantander, Spain

    Disclosures: Duran reports compensated advisory board roles with Ipsen, Merck Sharpe & Dohme, Novartis, Pharmacyclics and Roche; research funding from Roche; and assistance with expenses for medical meetings from Ipsen and Roche.

    See more from European Society for Medical Oncology Congress