Comparing Radical Prostatectomy and Brachytherapy for Localized Prostate Cancer

Radical prostatectomy and ultrasound- guided transperineal brachytherapy are both accepted treatment options for men with clinically localized prostate cancer. Investigators continue to argue over the relative effectiveness of each of these procedures, not only from the standpoint of cure, but also with regard to how each treatment affects quality of life. With the recent closure of a prospective, randomized trial addressing these issues (the Surgical Prostatectomy Interstitial Radiation Intervention Trial, or SPIRIT) due to lack of patient accrual, it is unlikely that a direct comparison of these techniques will be performed in the foreseeable future. Therefore, several investigators have reviewed institutional series in an attempt to determine which is the "better" therapy. To this list we can add the manuscript by Quaranta et al, who attempt to compare outcomes after radical prostatectomy or brachytherapy for clinically localized prostate cancer using institutional series that reported outcomes on at least 100 patients. Unfortunately, this report does little to resolve the debate. Inherent Problems in the Analysis
The primary question-are radical prostatectomy and brachytherapy equally effective in the treatment of low-risk prostate cancer-cannot be answered by comparing institutional reports. The patient populations are too different to make meaningful conclusions. Using a risk-group strategy to try to adjust for differences in clinical parameters is problematic because, even within the same risk group, patients do not have the same risk of cancer recurrence.[1] Studies examining risk-group strategies have suggested that this technique of lumping patients together results in a heterogenous mixture of patients who may differ with respect to outcome. So a group of intermediate- risk patients treated with one particular treatment may differ considerably from a group selected according to the same definition of intermediate risk when used to describe patients treated with a different intervention. Therefore, the authors' conclusion-that current information suggests radical prostatectomy and brachytherapy are equivalent-is not valid based on their analysis. In addition to the statistical issues, there are several other flaws in this analysis. Five-year biochemical outcomes are inadequate for meaningful assessment after radiation therapy. This is primarily based on use of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical recurrence, which requires three consecutive rises in serum prostate-specific antigen (PSA) levels, each drawn at least 3 months apart, before a patient is considered a failure. Since it takes up to 2 years to reach a PSA nadir and rising PSA levels take time to occur, the inclusion of brachytherapy studies with short median follow-up likely underestimates the true recurrence rate. While the authors emphasize the flattening of the disease-free survival curve following brachytherapy (Figure 2), this likely represents few patients with long-term follow-up and the delay in detecting biochemical recurrence among men treated with radiation therapy. This is further confounded by the fact that many men undergoing brachytherapy receive hormonal therapy. Even if such treatment is given for only 3 months, the impact on testosterone levels and therefore serum PSA levels can be much longer, again making interpretation of failure problematic. Incomplete Side-Effect Discussion
The manuscript is certainly written from the perspective of a radiation oncologist, as results are presented with a bias toward brachytherapy. This is most evident in the discussion of each treatment's side-effect profile. A listing of side effects that does not mention postbrachytherapy irritative voiding symptoms is inadequate. While incontinence is briefly discussed, the authors do not provide any data regarding voiding dysfunction after brachytherapy. In addition, in their discussion of rectal toxicity, the authors provide one sentence regarding brachytherapy: "Rectal toxicity in patients treated with brachytherapy is generally mild, and severe toxicity is rare." The remaining discussion cites the high incidence of rectal injury and stool leakage during perineal prostatectomy, a procedure rarely performed in centers of excellence. Such selective reporting of complication data provides little to support one treatment over another. Finally, it is difficult to compare treatments when different quality-oflife end points are involved. Each event-cure, erectile dysfunction, urinary dysfunction, rectal toxicity-cannot be viewed in isolation. It is difficult to weigh how patients feel about impotence relative to incontinence, irritative voiding, or bowel dysfunction. It is also difficult to weight quality-oflife issues against disease control ability. Trading one for the other requires methods such as utility assessment, but the institutional comparisons being considered here do not permit these analyses to be undertaken. Conclusions
In summary, this article does little to resolve the debate regarding the optimal treatment for clinically localized prostate cancer. Institutional series do not contain comparable groups of patients to allow such comparisons to be performed. In addition, selective data presentation skews the reader's ability to interpret the results presented.