Paulson DP, Lin GH, Hinshaw W, and Stephani S
The Uro-Oncology Research Group
Last Modified: August 18, 2006
Reviewed by: Drew Moghanaki MD, MPH
Source: The Journal of Urology 1982. Sep;128(3):502-4.
Initially, 59 and 47 patients were randomized to radiation and prostatectomy, respectively. However, there were patients in both groups who failed to receive their assigned treatments, and cross-over to the opposite treatment arm was allowed.
Analysis was performed by treatment given, and not by treatment intention.
The primary endpoint of failure was recorded as any 2 consecutive rises in PAP levels, or abnormal chest x-ray or bone scan.
Follow-up consisted of periodic physical examination, PAP levels, CXR, and bone scans. The trial was closed early due to inadequate funding, and after study closure, follow-up appointments were only encouraged, but not required.
Other problems include the 4-envelope randomization scheme, which is fraught with potential selection bias, as it allows the opportunity to know the randomization in up to 50% of patients. In addition, not all institutions completed the 4-patient randomization, raising concern for physician selection bias. The analysis was not intent-to-treat and permitted cross-over, neither of which is generally accepted practice in randomized studies. Pathologic stage C patients were excluded from the surgical arm but allowed in the radiation arm, and the rate of failure in the radiotherapy arm resembles a pattern more consistent with stage C patients. No median follow-up time is given, and no overall survival data are reported.
The authors do attempt to describe the radiotherapy technique; however, the information provided suggests a non-standard fractionation scheme during the whole-pelvis component of treatment. Additionally, although unpublished, it has been suggested that the vast majority of patients received only 6,500 cGy, which by today's standards is known to be sub-therapeutic.
There was no tissue validation reported for relapse, and no quality assurance was maintained for abnormal bone scans. Multiple reports have demonstrated a >30% rate of false positive bone scans in patients treated for prostate cancer. Additionally, it has become clear over time that elevated PAP levels can result from radiotherapy to bone, confounding this variable as a marker of failure in the radiotherapy group.
Regarding the current utility of this study in the treatment decision-making process for patients with locally confined prostate adenocarcinoma, it should be emphasized that the surgical procedure used, prostatectomy, has since been replaced with radical prostatectomy as the standard uro-oncologic approach for prostate cancer. Additionally, a 40% rate of incontinence among patients undergoing surgery is considered unacceptably high by today's standards.
It is unfortunate that the methodologic flaws present within the study preclude any meaningful conclusions regarding prostatectomy versus radiotherapy in organ-confined prostate cancer. Modern retrospective analyses have repeatedly suggested equivalency of surgery versus radiation in this patient population.3 Ultimately, however, it would be useful if an appropriately designed prospective randomized trial addressing this question could be conducted.
1 Re: Radical surgery versus radiotherapy for adenocarcinoma of the prostate. Byhardt RW, Greenlaw RH, Jensen R, Nag S, Roswit B, Stephani S, Woodward K. Journal of Urology 1983 Dec;130(6):1205-6.
2 More on the Uro-Oncology Research Group report of radical surgery vs. radiotherapy for adenocarcinoma of the prostate. Int J Radiat Oncol Biol Phys. 1988 May;14(5):1053-4.
3 Pretreatment PSA velocity and risk of death from prostate cancer following external beam radiation therapy. JAMA. 2005 Jul 27;294(4):440-7.