• © 2002 by American Society of Clinical Oncology

Comparing Contemporary Surgery to External-Beam Radiotherapy for Clinically Localized Prostate Cancer

In this issue of the Journal of Clinical Oncology, Kupelian et al¹ retrospectively compared the outcomes of patients with localized prostate cancer treated with external-beam radiotherapy or with radical prostatectomy. The authors demonstrate that when stratified by prognostic risk groups, there are no obvious differences between these two treatment approaches. The data support the results of previous studies from the same institution and other reports comparing radiotherapy to prostatectomy.^2,3

Kupelian et al¹ were able to demonstrate the efficacy of these two treatments only when the analysis was restricted to the radiotherapy patients who received dose levels greater than 72 Gy. In fact, for each risk group analyzed as favorable, intermediate, and unfavorable, the outcome after radical prostatectomy was consistently superior to that of patients treated with lower-dose radiotherapy. These findings are not at all surprising. There is ample evidence in the literature to demonstrate that higher radiation dose levels are associated with improved biochemical and local control outcomes for patients with clinically localized prostate cancer.^4-7 In a randomized trial, the outcome of patients with intermediate-risk prognostic features treated to 78 Gy was found to be superior to that of patients treated to dose levels of 70 Gy.⁴ We have also observed significant improvements of the prostate-specific antigen (PSA) relapse-free survival rates for all prognostic risk groups among those who received 81 Gy compared with those who received 75.6 Gy and lower doses.⁶ Taken together, these data clearly indicate that higher radiation dose levels are essential for maximal tumor control and that lower doses do not represent standard of care. Therefore, patients treated to conventional dose levels of 64.8 to 70.2 Gy should not be considered an appropriate cohort to be used as a meaningful comparison with other treatment modalities, such as radical prostatectomy.

Nevertheless, there are recognized limitations to the comparison made by Kupelian et al.¹ Aside from its retrospective nature, the follow-up times for the patients treated with higher versus lower radiation dose levels were different (62 v 42 months), which could explain the superior PSA outcomes among those who received more than 72 Gy. Indeed, the authors recognize that longer follow-up of these two treatment groups will be needed to confirm that these differences will be maintained. Others have raised issues regarding the potential bias of comparing patients treated sequentially at one institution during different eras, where more favorable outcomes have been associated with patients treated more recently.⁸ Treatment morbidity issues and quality-of-life factors, issues not addressed in this report, also play a critical role for the patient with localized prostate cancer who must make the difficult choice of choosing among various treatment options.

An additional limitation of this study is that a simplified (although popular) prognostic risk group classification scheme was used based on the presence of tumor-related variables, including the PSA, Gleason score, and clinical stage. It is likely, for instance, that a PSA value of 3.0 ng/mL would be associated with a different outcome than a value of 9.9 ng/mL, even when the other prognostic variables are identical. Risk group stratification schemes, while simple and convenient to use, may not take advantage of all the prognostic data available. As a result, such methods suffer from potential loss of predictive accuracy and represent an inefficient use of data and classification. More sophisticated models relying on the use of continuous risk scales, such as nomograms, have been used, and the data suggest that these models may be more accurate for outcome prediction.⁹ It may be possible to identify more precisely various cohorts of patients who will have a more favorable outcome with radical prostatectomy or some form of radiotherapy, with further refinements in prognostic risk group stratification methods. Such prognostic models will be more reliable predictors of outcome if they incorporate biologic or molecular markers that could better discriminate for tumors with radioresistance or greater metastatic potential.

However, in the absence of randomized trials comparing optimal radiotherapy to radical prostatectomy, we have no choice but to resort to such retrospective comparisons to understand how similar groups of patients fare with available treatments. The strength of this report is that the outcome of patients who received radiation therapy delivered to an optimal dose was comparable to that of patients treated with surgery. The reader must therefore exercise a great deal of caution in interpreting publications that tout comparisons of these two approaches, when the radiation doses are the “traditional” yet suboptimal dose levels of 64.8 to 70.2 Gy. Such analyses simply amount to comparing “antiquated radiation” to “modern surgery.” Comparisons like these should no longer be considered appropriate.