Adjuvant Likely Bests Salvage Radiation in High-Risk Prostate Cancer

By Marilynn Larkin

June 15, 2021

NEW YORK (Reuters Health) - Adjuvant radiation following radical prostatectomy (RP) seemed more effective in reducing all-cause mortality (ACM) than salvage radiation in men with high-risk prostate cancer in a large retrospective study.

"The study will likely change the standard of care," Dr. Anthony D'Amico of Brigham and Women's Hospital in Boston told Reuters Health by phone. "Three randomized trials published in September 2020 concluded that delivering radiation therapy (RT) after surgery...when the PSA rises signaling recurrence (i.e., early sRT), as opposed to when the PSA is undetectable (i.e., adjuvant RT), did not compromise subsequent cancer progression." (https://bit.ly/36zmPEx, https://bit.ly/3gmpmq5 and https://bit.ly/36yZ6o1)

"So now, no one is referred for adjuvant radiation," he said.

"However, those trials may have missed the benefit of adjuvant RT because a minority of men (9% to 17% of the study cohorts) were found to have adverse factors at prostatectomy that are associated with cancer progression and death from prostate cancer - i.e., Gleason eight to 10 or extension of cancer into nodes, or beyond the prostate, into the capsule or the seminal vesicles," he said. "The studies were not powered actually to look within each of those categories."

"The second problem is they analyzed the trials early - at the time of PSA failure instead of metastasis," he said. "As a result, there was no longer time to have adjuvant treatment. If adjuvant treatment is going to have any benefit, it's while the burden is still likely local and microscopic."

As reported in the Journal of Clinical Oncology, Dr. D'Amico and colleagues evaluated the impact of adjuvant versus early sRT on ACM risk in more than 26,000 men (median age,62) with pT2-4N0 or N1M0 prostate cancer treated from 1989 to 2016.

After a median follow-up of 8.16 years, 2,104 (8.06%) men had died, and about a quarter (25.62%) of the deaths were from prostate cancer.

After excluding men with a persistent PSA, and adjustment for all relevant factors as well as androgen deprivation therapy (ADT), adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at radical prostatectomy, whether men with pN1 PC were excluded (0.33) or included (0.66).

The authors note, "This association of reduced ACM risk with adjuvant compared with early sRT is strengthened given that men who underwent adjuvant compared with early sRT had less favorable PC prognostic factor distributions, which should have placed them at higher risk for needing sADT and dying. However, they had lower rates of sADT use and a lower ACM risk."

Dr. D'Amico added, "What's driving the ACM reduction is prostate cancer-specific mortality reduction. So it's not some confounding factor, like healthier men are more likely to get adjuvant radiation, and therefore live longer."

Dr. Jorge Caso, an oncologic urologist at Miami Cancer Institute, part of Baptist Health South Florida, commented in an email to Reuters Health, "The highest quality studies to date (RCTs) have not shown the superiority of this treatment."

"Keeping in mind that the conflicting data are from a retrospective cohort study, which by its nature may contain other biases, this should focus additional study efforts in this patient population but would likely not rise to the evidence level that would cause guidelines to change," he said.

"The cohorts from which they derive their data are from different hospital systems and varying time periods, during which, for example, surgical techniques have advanced greatly," he noted. "Pathological assessments/Gleason grading have changed, different hormonal suppression protocols may have been present, etc., all of which may influenced the findings."

"Additionally, we do not know the contribution from each of the institutions to the total patient population that was studied, and variability of radiation and androgen deprivation protocols between these institutions could have outsized effects," he said.

Nonetheless, he added, "Clinicians who feel their patients require a more proactive approach may choose after careful discussion of risks and benefits to offer adjuvant radiation rather than wait for salvage radiation in well selected patients. This study offers some justification for this approach, at least until further elucidated in future trials."

SOURCE: https://bit.ly/2Tz9vLS Journal of Clinical Oncology, online June 4, 2021.

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