Paradigm Shift: Radiation a New Standard in Prostate Cancer with Low Metastatic Burden

For patients with newly diagnosed metastatic prostate ­cancer, current standard management is androgen-deprivation therapy plus docetaxel (Taxotere). Contrary to previous assumptions, radiation to the primary tumor improves survival in men with low metastatic disease burden. This new finding came from the preplanned analysis of the multiarm, multistage STAMPEDE study presented at the ESMO 2018 Congress by lead investigator Chris C. Parker, MD, FRCR, MRCP, Consultant Clinical Oncologist, Royal Marsden NHS Foundation Trust, Sutton, England. The study was simultaneously published online in the Lancet.1

“Until now, we thought that if the cancer had spread, there was no point in treating prostate itself with surgery or radiation,” Dr Parker said. “We hypothesized that the benefit of radiation to the primary tumor would likely be greater in men with lower metastatic disease burden,” he added.

“We think these are robust and reliable findings. Androgen-deprivation therapy alone is no longer adequate for men with pelvic nodal disease. Going forward, prostate radiation should be a standard treatment option for men with newly diagnosed metastatic prostate cancer and low metastatic disease burden,” Dr Parker stated.

This comparison of radiation or no radiation to the primary tumor was embedded in the randomized phase 3 clinical trial, STAMPEDE. The researchers hypothesized that untreated primary tumors could contribute to overall disease progression and shorter survival in men with metastatic prostate cancer.

Study Details

The study enrolled 2061 men with newly diagnosed metastatic prostate cancer. The median age was 68 years; median prostate-specific antigen was 97 ng/mL; 18% of patients received early docetaxel treatment at investigator’s discretion.

Higher burden of disease in prostate cancer was defined as ≥4 bone metastases, with at least 1 metastasis outside the axial skeleton and/or visceral metastases (54% of study participants). The remainder of patients were characterized as lower disease burden.

Participants were randomized to standard-of-care treatment (lifelong androgen-deprivation therapy with or without docetaxel) or standard of care plus radiation to the prostate. Radiation could be given on 2 different schedules according to investigator’s choice: daily (55 Gy in fractions for 4 weeks) or weekly (36 Gy in 6 fractions every 6 weeks).

Radiation to the prostate improved failure-free survival (ie, biochemical failure, local failure, or death) but did not improve overall survival (OS) in the group of patients with high burden of metastatic disease. A total of 391 deaths were reported in the control arm and 370 in the radiation arm. The 3-year survival rates were 62% for the standard-of-care arm and 65% for the radiation arm.

Radiation to the prostate improved OS by almost one-third (32%) in the 819 men with low burden of metastatic disease. The 3-year OS rates were 81% in the radiation therapy arm versus 73% in the standard-of-care arm, a significant difference (P = .007).

By contrast, no improvement in OS was seen with radiation to the prostate in the 1120 men with higher metastatic burden, with a 3-year OS of 53% versus 54%, respectively.

Radiotherapy to the prostate was well-tolerated, with 5% of patients experiencing grade 3 to 4 adverse events during treatment and 4% after treatment.

Formal discussant Robert Bristow, MD, PhD, FRCPC, Director, Manchester Cancer Research Centre, England, said, “Radiation to the prostate should be considered standard of care. The treatment is well-tolerated, including in the elderly, and it is relatively effective and cheap. We would like to know whether surgery would achieve the same results.”

“For the first time, this study provides evidence that treating the local primary tumor is associated with improvement in overall survival in men with metastatic prostate cancer and minimal disseminated disease,” commented ESMO Expert Karim Fizazi, MD, PhD, Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France.


Reference

  1. Parker CC, James ND, Brawley CD, et al; for the STAMPEDE investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE). Lancet. 2018 Oct 18. Epub ahead of print.

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