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Radiation reduces failure risk in newly diagnosed nonmetastatic prostate cancer
Routine use of radiation therapy appeared to prolong failure-free survival among patients with nonmetastatic, newly diagnosed prostate cancer regardless of nodal status, according to findings from the control arm of the STAMPEDE trial.
The STAMPEDE trial is a multiarm, multistage study of men with prostate cancer starting first-line hormone therapy. Researchers are evaluating the impact of the addition of treatments to hormone-based therapy. The control arm of the study evaluates the use of hormone therapy with radiotherapy when appropriate — radiation was optional for all nonmetastatic patients at the start of the trial, but it became mandatory for the node-negative subgroup in November 2011 based on data from other reports.
“The control arm (standard-of-care only) of STAMPEDE, a large ongoing, high recruiting trial, provides important data on the natural history of patients with prostate cancer starting long-term hormone therapy,” Melissa R. Spears, MSc, BSc, a member of the Medical Research Council in the U.K., told HEMONC TODAY. “This is data which can be released without compromising the ongoing trial and the validity of future results.
“As such it is important that where possible this be done both to inform the set-up of other trials as well as detail outcomes in specific patient groups where data is limited.”
Spears and colleagues evaluated data from 721 nonmetastatic patients (median age at entry, 66 years; range, 61-72) enrolled on the control arm between Oct. 5, 2005 to May 1, 2014 to consider the effect of radiotherapy on failure-free survival (FFS) based on nodal involvement. Median PSA level in the cohort was 43 ng/mL (range, 18-88) at baseline.
FFS and OS served as the primary endpoints.
After a median follow-up of 17 months, 40 men died, 31 of whom died of their prostate cancer.
Overall, 96% (95% CI, 93-97) of this cohort achieved 2-year OS and 80% (95% CI, 72-86) achieved 5-year OS.
The 2-year FFS rate was 77% (95% CI, 73-81), and median FFS was 63 months (range, 26-not yet reached).
More patients with nodal involvement at randomization experienced an FFS event (27% vs. 17%; HR = 2.02; 95% CI, 1.46-2.81). Five-year FFS was 47% (95% CI, 36-58) among node-positive patients and 60% (95% CI, 50-68) among node-negative patients.
Researchers then evaluated data based on nodal status and whether radiation therapy was planned in 357 men who met criteria for inclusion. In the node-negative cohort treated before November 2011, 59 had no radiation planned and 121 did. In the node-positive cohort, 80 had no radiation planned and 97 did.
FFS outcomes appeared improved among patients planned for radiation therapy in the node-negative (HR = 0.33; 95% CI, 0.18-0.61) and node-positive cohorts (HR = 0.48; 95% CI, 0.29-0.79).
“For men with non-metastatic prostate cancer there is limited information on their disease as their prognosis is relatively good,” Spears said. “We highlighted the important role of radiotherapy in this population. Of note is the clear improvement in FFS in both node-negative and node-positive M0 patients treated with radical radiotherapy; the former consistent with published trials, the latter unlikely to ever be assessed in a randomized trial. Long-term follow-up will assess whether this effect on delaying progression translates into a survival benefit.”
The toxicity profile did not differ based on nodal positivity or negativity, and no grade 4 or grade 5 adverse events occurred.
“Previous widespread concerns that radiotherapy was inappropriate in patients with high-risk nonmetastatic disease, due to high probability of occult metastases, appear to be misplaced,” Spears told HEMONC TODAY. “These data support the routine use of radiotherapy in men with node-positive non-metastatic disease. As with all trial analyses, application of results in a non-trial setting should take into consideration the trial eligibility and of course radiotherapy should only be considered in suitably fit patients.
“STAMPEDE is currently collecting randomized data on the value of prostate radiotherapy for men with metastatic disease. If positive, this will further support the role of radiotherapy in the node-positive M0 setting.”
Although it is “probably true” that the addition of external-beam radiation therapy (EBRT) to androgen deprivation therapy improves outcomes in node-positive prostate cancer, there are several limitations to these findings, Anthony V. D’Amico, MD, PhD, chief of the division of genitourinary radiation oncology at Dana-Farber Cancer Institute and a professor of radiation oncology at Harvard Medical School, wrote in an accompanying editorial.
Concerns include that radiation therapy was prescribed by physician’s choice and wasn’t randomized, short follow-up and that FFS driven by PSA will make it difficult to determine an impact on OS. Further, OS wasn’t evaluable as an endpoint, and with 40 deaths in the cohort — 9 of which could not be attributed to prostate cancer — a competing risk vs. Cox regression model may have been more appropriate to analyze the endpoints of time-to-first failure or death.
“Looking ahead, we await the discovery of predictive biomarkers of resistance to conventional ADT and EBRT in order to personalize the treatment approach in an otherwise healthy man with node-positive prostate cancer with respect to the use of both pelvic and prostate EBRT to enhance locoregional control and appropriate systemic therapies to sterilize any remaining occult micrometastatic disease,” he wrote. “In the interim, comorbidity and androgen receptor splice variant-7 status may provide a rational basis and starting point for patient selection for nodal and prostate EBRT and ADT as a treatment option.” – by Anthony SanFilippo
For more information:
Melissa R. Spears, MSc, BSc, can be contacted at m.spears@ucl.ac.uk.
Disclosure: The study was funded in part by Astellas, Janssen, Novartis, Pfizer and Sanofi. The researchers and D’Amico report no relevant financial disclosures.