Is radiation therapy any better than active surveillance for localized prostate cancer?


An updated, systematic review just published in Annals of Internal Medicine states that it is impossible to come to any conclusions about the efficacy of radiation therapy compared with active surveillance or watchful  waiting for the management of localized prostate cancer because of the absence of any high-quality, comparative data.

Of course we are all waiting to find out the results of the ongoing ProtecT trial, which is being carried out in the United Kingdom. In that trial, > 2,000 men who meet specific diagnostic criteria have been allowed to select whether they wanted to have immediate surgery, immediate radiation therapy, or active surveillance as their treatment of choice for localized prostate cancer. The initial results of this study are projected in December 2013, so we have a while to wait yet. However, it may take until 2025 or thereabouts before the ProtecT study can provide definitive, comparative data about a survival benefit associated with one of other form of management (overall or for identifiable subgroups of patients).

In the meantime, however, the radiation oncology community is likely to be less than enthusiastic about the new article by Bannuru et al.

The authors carried out a careful search of MEDLINE and the Cochrane Central Register of Controlled Trials (from 2007 through March 2011) in order to update their prior systematic analysis on the same topic (originally carried out for the April 2010 MEDCAC assessment of the value of radiation therapy in the management of localized prostate cancer).

They tried to identify all published English-language comparative studies involving adults with localized prostate cancer who either had first-line radiation therapy or received no initial treatment. For publications meeting pre-specified  criteria, they then extracted information on study design, potential bias, sample characteristics, interventions, and outcomes and rated the strength of overall evidence.

Here is what they found:

  • 75 studies met the inclusion criteria
    • 10 were randomized, controlled trials (RCTs).
    • 65 were non-randomized studies.
  • None of the RCTs compared radiation therapy with no treatment or no initial treatment.
  • Among the 10 RCTs
    • Two compared differing combinations of radiation therapies.
    • Seven compared differing doses and fraction sizes of external-beam radiation therapy (EBRT).
    • One compared differing forms of low-dose rate radiation therapy.
  • There was consistent evidence of  moderate strength that a higher doses of EBRT are associated with increased rates of long-term biochemical control compared with lower doses.
  • The body of evidence was rated as insufficient for all other comparisons.
The authors are careful to note that their findings are limited by the facts that (a) the published papers are inconsistent in the way that they define and report outcomes after radiation therapy and (b) much of the available evidence comes from observational studies with treatment selection biases.
The findings from this study will be no surprise to the well-informed prostate cancer patient or support group leader. At least in the case of surgery, we now have data from two large RCTs suggesting that (with 12+ years of follow-up) the survival benefits of radical prostatectomy are limited to men of 65 and younger and may also be limited to those with more aggressive forms of disease. The pressure to have accurate, comparative survival data on the benefits (if any) of immediate radiation therapy compared to careful monitoring in men ≥ 65 years of age diagnosed with localized prostate cancer is now increasing rapidly.

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