Surgery vs. radiation therapy in first-line treatment of prostate cancer: a travesty

Almost exactly a year ago, we commented unfavorably on a media release issued by the European Association for Urology (EAU). The media release referred to a presentation made by Sooriakumaran et al. at the annual meeting of the EAU in 2013.

The full text of a paper by Sooriakumaran et al., based on their original presentation, has now been published in the British Medical Journal. Having read it with care, we continue to be horrified by the lack of scientific and clinical rigor inherent in this paper, let alone the utter lack of validity of the conclusions that are drawn, which includes the ludicrous idea that radiation therapy is an appropriate form of first-line treatment for men diagnosed with metastatic prostate cancer. How this paper ever passed peer review is beyond us.

No one questions the fact that surgery is an effective form of treatment for appropriately selected (and appropriately informed) patients with localized forms of prostate cancer. No one questions the fact that radiation therapy (commonly in association with some form of androgen deprivation therapy) is an effective form of treatment for appropriately selected (and appropriately informed) patients with more advanced forms of prostate cancer that have progressed to the lymph nodes (when surgery is commonly not effective on its own). No one today questions the idea that radiation therapy can also be effective in the treatment of men with localized prostate cancer who — for whatever reason — are inappropriate candidates for surgery (or just prefer not to have surgery). But of course surgery and radiation therapy come with significant risk for complications and side effects in all patients; neither form of treatment is necessarily curative in all men with localized disease; neither form of treatment is effective in any man with metastatic disease; and the critical issue is ensuring that the patient, in making his decisions about appropriate treatment for him as an individual, is given a full and accurate understanding of the risk/benefit equation in his particular case.

The paper by Sooriakumaran and his colleagues appears to ignore almost all of the complexities and subtleties that are key to the selection of an appropriate management strategy for a newly diagnosed prostate cancer patient in 2014. It lumps into poorly defined categories some 34,000+ patients diagnosed in Sweden in the 1990s — many diagnosed with no benefit from the use of PSA testing, who were therefore diagnosed on the basis of clinical symptoms alone. Based on the currently outmoded forms of treatment given to those patients, it then comes to a series of unjustifiable conclusions about the benefits of surgery as opposed to radiation therapy and states categorically that these conclusions are applicable to patients today.

If one takes the time to read some of the comments already submitted to the British Medcical Journal about this paper, you will quickly see that many of the commentators (including leading members of the urology and the radiation oncology community) reacted to this paper with a similar sense of outrage to the feelings expressed here.

The “New” Prostate Cancer InfoLink submits that this paper by Sooriakumaran et al. represents the very worst type of “comparative effectiveness” research. It starts with a naive set of assumptions about how treatments were being selected for prostate cancer patients in Sweden nearly 20 years ago. It compounds that naivety by assuming that the forms of treatment being used 15 to 20 years ago are being applied in the same ways today. And as a consequence it reaches conclusions that are are irrelevant to any physician qualified to treat prostate cancer in 2014 and to his or her patients.

This is not to say that the data generated by Sooriakumaran and his colleagues are of no interest; they are certainly of interest, but that interest is historic. It is qualified by the fact that highly relevant data on these patients is either not available or was not included in the analysis. And the question that should have been addressed was not whether these data prove that surgery is a more appropriate form of treatment than radiation therapy for men with earlier stages of prostate cancer today. Rather, these data should be used to address questions about

  • The extent to which the decisions about treatment being made in Sweden in the mid- to late 1990s have in fact been justified by the outcomes of the patients being treated at that time
  • What these data can tell us (if anything) about how to make better decisions  about treatment selection in similar patients today

The “New” Prostate Cancer InfoLink believes that a medical journal with the stature of the British Medical Journal should be ashamed of the failure of its editors and reviewers to demand major modifications to this paper prior to its publication. The paper in its current form offers no useful guidance to anyone about the management of prostate cancer today, and it reaches some highly misleading conlusions that have no basis in fact whatsoever — largely as a consequence of the way that groups of patients were inappropriately lumped together in the analysis.

Last but not least, the paper takes absolutely no sensible account of the ages, the co-morbidities, and the side effects and complications suffered of the 34,000+ patients on which the data is based. Since these factors are critical to the appropriate management of men with prostate cancer, the failure to assess these factors with any degree of accuracy further undermines the relevance of the entire analysis.

4 Responses

  1. Briefly reading the comments, it seems to me that the surgeons comments are more favorable to the conclusions than the radiation oncologists, which makes me wonder if there is a bias of one type of therapy over another based on the speciality of the practitioner.

  2. Dear John:

    Inevitably there is some built-in bias on the part of the commentators, which is why it is very valuable to note carefully that some of the negative comments on the article are coming from respected members of the surgical community and not exculsively from the radiation oncology community.

  3. As a person who sometimes writes while in the grip of a heated emotion, I wonder if your scathing judgment on the paper might possibly have spilled over into an intemperate assessment of a proposition that may be worth considering, even if the paper you rightly blast is utterly incompetent to support it.

    You characterized as “ludicrous” the idea that radiation therapy might be an appropriate form of first-line treatment for men diagnosed with metastatic prostate cancer. I say, “Not necessarily.” The abscopal effect is real (though rare), not-implausible, and poorly understood. At present, there is no way to distinguish the tiny minority of men whose remote cancers will be affected by primary radiation from the vast majority of those who will see little or no such benefit. If good candidates could be distinguished, the peculiarities of their immune system (if indeed the abscopal effect is immune-related) would be worth studying.

    Certainly if I were newly diagnosed with metastatic prostate cancer and I had a close relative whose metastatic melanoma had responded abscopally, I would try radiation before debulking.

  4. Dear Paul:

    There are two different things goinng on here: (a) Can one treat areas of metastasis with radiation therapy? Sure one can, but there is no evidence to suggest that this can be done with surative intent. (b) Can one use radiation therapy to debulk the prostate and other surrounding tissues? Again, sure one can, but there is no evidence to suggest that this can be done with curative intent.

    From that perspective, the idea that radiation therapy is an appropriate form of first-line treatment for metastatic disease makes no sense whatsoever … although radiation therapy + ADT certainly may in appropriately selected patients.

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