Extraprostatic extension (EPE) alone is not enough to justify adjuvant radiation

Patrick Walsh and Nathan Laurentschuk have just published an opinion piece in European Urology taking issue with the 2013 AUA/ASTRO recommendation that adjuvant radiation is indicated for men with a pathological finding of extraprostatic extension (EPE, stage pT3a) after surgery, regardless of the surgical margin status. The combination of EPE and negative surgical margins is the most common adverse pathological finding post-surgery, accounting for 60 percent of such adverse findings. Therefore, the AUA/ASTRO guideline would lead to gross over-treatment if it were followed. They believe that it is fortunate that that guideline is increasingly ignored (see this earlier commentary).

They looked at the three randomized clinical trials of adjuvant radiation vs. wait-and-see, for evidence that EPE alone justified adjuvant radiation:

  • Although it concludes that all patients with EPE should have adjuvant radiation, SWOG 8794 never looked at that subgroup separately.
  • In ARO 96-02, men with EPE and negative margins received no statistically significant benefit in terms of freedom from biochemical failure from adjuvant radiation.
  • In EORTC 22911, not only was there no benefit, but this study found a 78 percent increased risk of dying among men with EPE and negative margins who received adjuvant radiation.

Walsh and Laurentschuck conclude with a set of recommendations about adjuvant radiation:

Who should NOT receive it:

  • Men with extraprostatic extension (capsular penetration) with negative margins
  • Men aged >70 yr unless they are very healthy and have high grade or positive margins
  • Men with bladder neck contractures or significant incontinence who have marginal indications

Who should receive it:

  • Men with Gleason ≥7 with positive surgical margins

Marginal benefit:

  • Men with positive seminal vesicles

In a commentary published in Practice Update, Christopher King, a radiation oncologist at UCLA, takes tissue with their recommendations. He argues that until the findings of randomized clinical trials provide more reliable data, current evidence does not justify adjuvant radiation based only on adverse pathology. Instead, based on several retrospective studies (reviewed on this site), he advocates waiting for some evidence of measurable disease. He believes that early salvage (before PSA rises above 0.2 ng/ml) will have equivalent oncological outcomes to adjuvant radiation, but will avoid the toxicity of over-treatment.

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

3 Responses

  1. There is a gradually increasing consensus that too many men used to receive immediate, adjuvant radiation therapy based on early pathological findings post-surgery. The general viewpoints referred to in this article (by Walsh and Lawrentschuk and by King) are arguably both valid. However, …

    We need to remind ourselves from time to time that the practice of medicine is an art and not just a science. Precise, individual decisions about who needs immediate, adjuvant radiation therapy and who can wait for early (or slightly later) salvage radiation therapy, in the end, are bound to depend on the clinical judgment of individual physicians in individual cases. Guidelines and opinions are designed and intended to help physicians and their patients reach conclusions that are appropriate as often as possible, but they are not intended to be “absolute truths.”

    The “New” Prostate Cancer InfoLink is pleased to see an increasing consensus emerge about the need to avoid excessive use of immediate, adjuvant radiation therapy post-surgery, but we also believe that it will always be possible to justify, with good reason, the use of immediate, adjuvant radiotherapy in some patients based on their individual pre- and post-surgical presentation and data.

  2. I suppose if the surgeon found significant amounts of cancer left behind outside of the capsule, throughout the seminal vesicles, or in dissected lymph nodes, there would be no point in waiting for ultrasensitive PSA confirmation. Outside of such gross residual tumor, it is hard for me to imagine a case where it would be unwise to wait at least 2 months for a ultrasensitive PSA (as in the Vesely et al. study).

    I should also mention that Epstein believes a distinction should be made between focal EPE (with only microscopic extension) and EPE with more significant extension. and recommends that pathologists record whether the extent of penetration into the fossa was focal or significant. His analysis showed that focal EPE has a similar recurrence prognosis as no EPE, unless the Gleason score was 9 or 10. He believes that focal EPE ought to have a different stage designation. We’ll have to see if his recommendation is taken up in the next AJCC staging manual. Here’s a link to his study.

  3. We are seeing evidence that, with apparent failure of surgical removal, particularly for men with higher risk, with higher Gleason scores, and I would expect with known seminal vesicle or lymph node migration, a move directly to chemotherapy accompanied by a testosterone-inactivating pharmaceutical is anticipated to have an effect on remaining cancer cell apoptosis. Failure of this protocol with subsequent rise in PSA would be more reason to then move to salvage radiation as well as continued ADT.

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