The Prostate Cancer Intervention Versus Observation Trial (PIVOT)
As described by Wilt et al in their review, the Prostate Cancer Intervention Versus Observation Trial (PIVOT) is asking very important questions about the effect of surgical treatment vs observation, with delayed androgen deprivation available to both groups, in patients with localized prostate cancer. Clinicians who have suffered with the old Uro-Oncology Trial comparison of prostatectomy vs radiation hope that PIVOT provides answers rather than confusion.
PIVOT: The Radiation Oncologist's Friend?
As described by Wilt et al in their review, the Prostate Cancer InterventionVersus Observation
Trial (PIVOT) is asking very important questions about the effect of surgicaltreatment vs observation, with delayed androgen deprivation available toboth groups, in patients with localized prostate cancer. Clinicians whohave suffered with the old Uro-Oncology Trial comparison of prostatectomyvs radiation hope that PIVOT provides answers rather than confusion.
It is reassuring that PIVOT is attempting to access representative patients,although patient accrual is proceeding at a much slower rate than was anticipated.This has required a decrease in the final number of patients from 2,000to 1,050, as well as an extension in the time for case accession from 3to 7 years. When this 7 years is combined with the planned 8- to 15-yearfollow-up, it is clear that PIVOT will be a study conducted by young men.
As best I can tell, the radiation oncology community was not invitedto this party because of a basic prejudice of the organizers that thereis a difference in the success of treatment with prostatectomy or radiation.I guess it was too much of a stretch for the trial to have compared bothsuccessful treatments to observation. If surgery proves worse or no betterthan observation, however, radiation will still be left for definitivetreatment!
I also suspect that the Veterans Affairs (VA) system is the only health-caresegment in the United States in which 17% of eligible patients would agreeto randomization to this clinical trial.
Criticisms of the Study Design
I have three criticisms of the study design:
- Permitting patients with pretreatment prostate-specific antigen (PSA)values of 20 to 50 ng/mL to participate in the trial permits the inclusionof a group of patients with a 70% to 95% risk of nonlocalized disease thatis not curable by surgery. This defeats the main purpose of the study.
- Including patients with presurgical hormonal downstaging is a veryserious error. The 3 to 6 months of androgen deprivation will delay thefailure pattern by 2 to 4 years, confusing the important end point of failureand, perhaps ultimately, the cause-specific death rate.
- Including patients who are 70 to 75 years old should again demonstratethe increase in mortality of prostatectomy in this age group, as well asthe decrease in quality-of-life functions, such as a higher rate of incontinence,following prostatectomy in this age group. Neither of these observationsneed to be proven again.
Two Final Questions
Finally, I have two questions about the design of this study and nationalacceptance of the results:
- Are there rules for stopping the trial if the morbidity of prostatectomyin the VA hospitals is excessive?
- Will non-VA-based urologic surgeons accept a negative result from surgeryin VA hospitals as representing the care that they deliver and stop performingprostatectomy, or will these surgeons dismiss the negative finding as uniqueto the study site, patients, and physicians?
