Watchful waiting as good as surgery for prostate cancer
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7365.613 (Published 21 September 2002) Cite this as: BMJ 2002;325:613All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
Is this statement really justified?
In the first place this conclusion would only be possible if the
study had been specifically designed as a non-inferiority/equivalence
trial and the resulting confidence limits lay within a prespecified - and
widely accepted -interval.
Secondly however, the primary endpoint is given as death from
prostate cancer. The result of the study was roughly a halving of the
risk of death from prostate cancer during follow up, the 95% confidence
interval for the hazard ratio being 0.27 to 0.91. Taking the results at
their face value,
this is direct evidence that radical prostatectomy is actually superior to
watchful waiting - contrary to the headline.
Thirdly, because all causes mortality was specified as a secondary
endpoint, the fact that the overall mortality rates were similar cannot be
taken as evidence that the treatments are equivalent - especially as all
cause mortality is also known to be an insensitive measure of efficacy
when the target disease is responsible for only a small fraction of all
deaths in the study population. This why screening trials use cause-
specific mortality rather than all-cause mortality as an endpoint.
Clearly other factors (quality of life and costs) need to be
considered before radical prostatectomy can be routinely offered instead
of watchful waiting, but these were not the primary aim of the study. I
do wonder whether such misleadingly negative statement would have been
acceptable if a treatment effect of the same magnitude had been observed
in a breast cancer trial, for example?
Competing interests: No competing interests
Not the whole truth
The headline for your article does not tell the whole truth about overall mortality for patients treated by radical prostatectomy over watchful waiting (1). The difference in overall survival at 8 years was 6.3% in favour of radical prostatectomy with a 95% confidence interval (CI) of -0.2 to 12.7%. Indeed, the absolute difference was not significant at conventional levels of significance, but the CI clearly shows that it may well be. Given that there were significant differences at 8 years in the development of metastases (14%, CI 8 to 20), local progression (42%, CI 35 to 48) and cause specific survival (6.6%,CI 2 to 11), the headline that there is no difference in survival seems harsh and does not reflect the totality of the evidence.
(1) Holmberg et al. A randomised trial comparing radical prostatectomy with watchful waiting in early prostate cancer.N Engl J Med 347: 781-9, 2002
Competing interests: No competing interests