Declining trend in the utilization of adjuvant radiation after surgery

A recent report in European Urology found that, in spite of three randomized clinical trials (RCTs) that proved the efficacy of immediate or adjuvant radiation following surgery with adverse pathology results compared to a wait-and-see approach, a lower percentage of such patients are actually getting adjuvant treatment. Why should this be?

I refer readers to a recent discussion of the issues involved, which I won’t fully reiterate here. First, let’s look at the abovementioned report by Sineshaw et al. The authors examined the records of 97,270 patients in the National Cancer Database where patients were found to have adverse pathological features (pT3/4 or positive surgical margins) in the period from 2005 to 2011. What they found is this:

  • Postoperative RT utilization declined from 9.1 to 7.3 percent.
  • Utilization declined with age: 8.5% in patients aged 18–59 to 6.8% in patients aged 70–79.
  • Utilization was 14 percent at community cancer programs compared to 7 percent at teaching/research centers.
  • Among those with stage pT3/4, utilization was 17 percent if they had positive margins, but 7 percent if they had negative margins.
  • Utilization was 17 percent among those with a pathologic Gleason score of 8-10 compared to 4 percent among those with Gleason score of 6 or less.

First, a note about the time frame examined in their study: only one of the three RCTs (Thompson et al., 2009) was published in that time frame. The Bolla et al. study was not published until 2012, and the Wiegel et al. study was not presented until 2013. The AUA/ASTRO guidelines advocating adjuvant radiation were not issued until 2013. So in the time frame examined in their study, we would not expect to see the full impact of those three studies and the new guidelines. This conflicts with the statement made in the publication:

In a retrospective analysis of 97 270 patients with prostate cancer, we showed that use of postoperative radiotherapy for adverse pathologic features has declined over time after the publication of findings from major randomized clinical trials and consensus guidelines supporting consideration of such therapy.

A report on the Medscape web site included comments from some highly respected radiation oncologists that are worth noting:

  • Jeffrey Michalski (Washington University, St. Louis) echoed the authors’ anachronistic lament that doctors were not following the evidence in the RCTs and guidelines.
  • Anthony D’Amico (Dana-Farber and Brigham and Women’s Hospital, Boston) pointed out that only one of the RCTs showed an advantage in metastasis-free and overall survival. He further explained that multiple risk factors may be a better indication for adjuvant radiation.
  • Michael Zelefsky (Memorial Sloan-Kettering Cancer Center, New York) noted that we don’t yet know if waiting for rising PSA would have any worse outcomes.
  • Howard Sandler (Cedars-Sinai, Los Angeles) blamed low utilization on urologists who don’t immediately refer adverse pathology patients to radiation oncologists. The patients are not being given options or provided with expertise.

Until the results of ongoing clinical trials on the benefit of early salvage radiation become available, this remains a difficult decision. A patient with adverse pathology would be wise to immediately begin discussions with a radiation oncologist, preferably at a teaching/research hospital, so that he fully understands what the risks and benefits are of waiting.

Editorial comment: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

2 Responses

  1. ASTRO/AUA Guideline Statement 3 standardizes adjuvant RT (ART) for all men with adverse pathologic features, regardless of extent, citing Grade A evidence from three randomized controlled trials (RCT’s ). But, much of what the authors define as ART was given at high PSA levels, and would be more correctly be classified as salvage RT (SRT). While the studies may have been Grade A, they were not all powered to distinguish between ART and SRT, and therefore they do not support giving RT when PSA is zero over a wait and see approach. Other studies have shown that ART leads to over-treatment more than 80% of the time (e.g., Kang et al., 2014). RT is an aggressive treatment with permanent impact on healthy body tissues (+1 for Zelefsky).

    Furthermore ART/SRT has proven efficacy only for PSA-only and clinical outcomes, whereas results for outcomes that may matter more to the patient (e.g. metastasis-free survival, overall survival) are mixed (+1 for D’Amico).

    Agreed, this is a difficult decision; agreed, the patient should consult a radiation oncologist.

  2. The percentage receiving adjuvant RT was small to begin with, so the decline of a couple more points doesn’t seem to be anything worth worrying about to me. Given the potential side effects of RT it’s not surprising that very few opt for it until they they actually have biochemical recurrence. That’s what I did and I don’t regret it … so far.

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