Radiation therapy in patients with +ve surgical margins

This month’s issue of AUA News carries two articles espousing different opinions about the appropriate use and timing of radiation therapy for prostate cancer patients who have positive surgical margins after an initial radical prostatectomy. AUA News is only available to subscribers, but support group leaders who are interested in these articles can probably get copies from local urologists with whom they work.

In the first article (see page 8), Drs Wirth and Froehner, who are based in Dresden, Germany, argue that temporarily delaying radiation therapy in most men with positive margins is the better strategy for the majority of patients. Their basic recommendations are as follows:

  • Only patients with high-risk disease and positive surgical margins should receive immediate postoperative adjuvant radiation therapy.
  • All other patients with positive surgical margins should be monitored closely for signs of a rising PSA (thus sparing these patients from the side effects of radiation unless it is absolutely necessary).
  • Salvage radiation therapy should be implemented in low- and intermediate-risk patients with positive surgical margins and a rising PSA as soon as PSA relapse occurs.
  • European guidelines suggest that salvage radiation in such patients should be implemented before the PSA level rises to 1.5 ng/ml, but there are good data suggesting that actually salvage radiation in such patients should probably be implemented before the PSA exceeds 0.5 ng/ml.

They take the position that “definitive evidence of the benefit of adjuvant radiotherapy for margin positive disease is still pending.” In their opinion, patients should be clearly informed of the significance of the available data (see below) from randomized clinical trials so that they can make their own decisions about immediate or deferred treatment.

In the second article (see page 10), Dr. Ritchie of Harvard Medical School takes the contrary position and argues that many patients with positive surgical margins should receive immediate, adjuvant radiation therapy because it is associated with a greater survival benefit. His specific recommendations can be summarized as follows:

  • All patients with significant positive surgical margins or pathological stage T3 disease should receive immediate, adjuvant radiation therapy.
  • Only those patients with “focal capsular extension alone and an unmeasurable PSA” should be followed and not radiated immediately, “as many of them will be cured with surgery alone.”

This is not just an academic discussion. The appropriate use of adjuvant radiation therapy in men who are at risk of progression following a radical prostatectomy is extremely complex, and — although three randomized clinical trials have been completed and published — the interpretation of the available data is difficult. The three trials that people should be aware of are as follows:

  • SWOG 8794, which was a US-based multi-institutional, randomized, prospective clinical trial that enrolled 425 patients with pathologically evident, locally advanced disease between 1988 and 1997; the patients were followed for at least 10 years (see Thompson et al.).
  • EORTC 22911, which was a European study that enrolled 1,005 patients with pathological T3 disease and/or positive surgical margins who were randomized to immediate radiation or “watchful waiting” — but the patients were only followed for 5 years (see Bolla et al. and Van der Kwast et al.).
  • The ARO 96-02/AUO AP 09/95 study, which enrolled 385 patients who were randomized to receive early adjuvant radiation therapy of “wait and see” observation after stratification by Gleason score and surgical margin status, and were again followed for 5 years (see Wiegel et al.).

The interpretations of the results of these studies would seem, to The “New” Prostate Cancer InfoLink, to be as much about attitudes to the relative benefits of overall survival and quality of life as the actual study data. If one wishes to come down on the side of the survival advocates, then the data do indeed support immediate adjuvant radiation — with the concomitant risks for the side effects of radiation therapy (and hormonal therapy if added). Conversely, if your prejudice is that quality of survival is at least as important as survival itself, there is good reason to come down on the side of delaying radiation therapy in all but the highest-risk patients, as suggested by Wirth and Froehner.

It is also worth pointing out that the two interpretations may reflect a culturally different attitude between the European and the American urology communities, with Europeans generally favoring quality of survival over survival alone, and Americans taking a pro-survival position.

What’s the bottom line?

The “New” Prostate Cancer InfoLink does not take a specific position. We believe that at the end of the day this is something that the individual patient has to make a decision about with the help of his urologist and a radiation oncologist. There is no “right” and there is no “wrong” — and even if we get more specific data from the major RADICALS trial being coordinated by the UK’s Medical Research Council, there may still be no right or wrong for the individual patient, because only the individual can make a risk analysis decision that is correct for himself as the patient. However, it is to be hoped that the RADICALS trial will, in due course, offer more definitive data on which to base that risk analysis.

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