Immediate adjuvant radiation therapy lowers mortality in high-risk prostate cancer
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Adjuvant radiation therapy immediately after surgery improved survival among men with prostate cancer and high-risk features, according to study results published in Journal of Clinical Oncology.
“Three prior randomized trials published in 2020 concluded that early salvage radiation should be the new standard of care for all men following prostate cancer surgery. However, there was a paucity of men with high-risk features in those studies,” Anthony V. D’Amico, MD, PhD, professor and chief of genitourinary radiation oncology at Dana-Farber/Brigham and Women’s Cancer Center, told Healio. “As a result, we simulated a group of 26,000 men from the U.S. and Germany to address whether adjuvant radiation therapy as opposed to early salvage may have a survival advantage in men with high-risk features at surgery, which was not properly addressed in prior randomized trials.”
D’Amico and colleagues evaluated the effect of adjuvant vs. early salvage radiation therapy on all-cause mortality risk among 26,118 men (median age, 62 years) treated for pT2-4N0 or N1M0 prostate cancer between 1989 and 2016. All men received treatment across four institutions in the U.S and Germany.
Median follow-up was 8.6 years.
Researchers reported 2,104 deaths, 25.62% of which were associated with prostate cancer. Overall, 2,424 men were at high risk for mortality despite surgery based on an adverse pathology, defined as positive pelvic lymph nodes (n = 933) or Gleason score of 8 to 10 prostate cancer and disease extending beyond the prostate. Of this group, 428 went on to receive adjuvant radiation therapy, 1,031 received early salvage radiation and 965 received no radiation.
Results of a sensitivity analysis that excluded men who had a persistent PSA showed adjuvant radiation therapy was associated with significantly lower all-cause mortality compared with early salvage radiation therapy among men with adverse pathology at radical prostatectomy when men with positive pelvic lymph nodes were included (adjusted HR = 0.66; 95% CI, 0.44-0.99) or excluded (aHR = 0.33; 95% CI, 0.13-0.85).
At 10 years follow-up after surgery, all-cause mortality was only 5% among men who received adjuvant radiation therapy compared with 22% among those who received early salvage radiation therapy.
These data indicate risk for death was lowered by one-third among men treated with adjuvant radiation therapy who had prostate cancer that spread to the lymph nodes, according to D’Amico.
“We observed a 67% reduction in death and 20% improvement in survival at 10 years with adjuvant vs. early salvage radiation therapy among the cohort of men with either positive pelvic lymph nodes or evidence of extra capsular extension or seminal vesical invasion in the context of Gleason score 8 to 10 prostate cancer,” D’Amico said.
A limitation of the study included that this is a retrospective study, and there could be potential for factors not controlled for, D’Amico added.
“However, the analysis that we performed was robust in that it adjusted for everything that was known,” he said. “Future research will look more deeply into men with positive nodes to see if adjuvant as opposed to early salvage is of benefit for men with one positive node vs. two or more positive nodes. There is controversy as to whether a single positive node mandates adjuvant radiation. But based upon our findings, we found an association irrespective of the number of positive nodes with respect to a survival advantage for adjuvant as opposed to early salvage radiation.”
For more information:
Anthony V. D’Amico, MD, PhD, can be reached at Brigham and Women’s Hospital and Dana Farber Cancer Institute, 75 Francis St., Boston, MA 02115; email: adamico@bwh.harvard.edu.
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