After two studies comparing radical prostatectomy with watchful waiting in men with prostate cancer yielded conflicting findings in absolute mortality difference (AMD), a group of investigators sought to explain the inconsistency.
Jing Xia, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, and colleagues summarized the findings of the two trials in Journal of the National Cancer Institute:
- In the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial, radical prostatectomy was shown to reduce prostate cancer deaths with a statistically significant AMD of 6.1% between that treatment and watchful waiting after 15 years.
- The Prostate Cancer Intervention Versus Observation Trial (PIVOT), conducted in the United States, produced an AMD of 3% after 12 years.
To determine whether a higher frequency of screen detection of prostate cancer in PIVOT could explain that study’s lower AMD finding, Xia’s group assumed that the SPCG-4 trial represented radical prostatectomy and prostate cancer survival in an unscreened population. Given the fraction of screen-detected prostate cancers in PIVOT, the researchers then adjusted prostate cancer survival using published estimates of overdiagnosis and lead time to evaluate the effect of screen detection on disease-specific deaths and the observed AMD.
On the basis of published estimates, Xia and coauthors assumed that 32% of screen-detected cancers were overdiagnosed, and assumed a mean lead time among non-overdiagnosed cancers of 7.7 years. When they adjusted prostate cancer survival for the 76% of patients in PIVOT whose tumors were screen-detected, they projected that the AMD after 12 years would be 2% based on variation in published estimates of overdiagnosis and mean lead time in the United States.
The team concluded that if radical prostatectomy efficacy and prostate cancer survival in the absence of screening are similar to that in the SPCG-4 trial, then the lower AMD in PIVOT is largely explained by overdiagnosis and lead time. According to the authors, if these findings are indeed the correct explanation, then a subset of men should not undergo radical prostatectomy, and identifying this subset should lead to a clearer understanding of the benefit of radical prostatectomy in the remaining cases.
“PIVOT should not be interpreted as evidence that [radical prostatectomy] is not efficacious in reducing prostate cancer mortality,” cautioned the investigators. “PIVOT should encourage us to develop tests to identify cases for which immediate treatment is beneficial.”