Merrick, Wallner, Butler, and Blasko have provided a timely and well articulated review on the proper use of supplemental external-beam radiation therapy in men treated with permanent prostate brachytherapy. These authors have contributed much to the prostate brachytherapy literature, and their opinions carry significant weight in this arena.

As the authors state, the reasons to add supplemental external-beam radiation therapy are to enhance the periprostatic dose, to escalate the intraprostatic dose, to rectify technically inadequate implants, and to treat the seminal vesicles and/or pelvic lymph nodes in their entirety. The authors then consider each of these issues by presenting retrospective data that suggest supplemental external-beam radiation is unnecessary.

External-Beam Radiation Reconsidered

The distilled version of their argument is that (1) extraprostatic seed placement provides enough dose laterally to treat extraprostatic extension adequately; (2) intraprostatic doses achieved with brachytherapy alone are high enough; (3) external-beam radiation therapy shouldn’t be needed to "spackle" a poor implant, because improved computer-based treatment planning using wide margins, attention to detail, and intraoperative dosimetry should prevent such incidents, and (4) if good technique is applied, only patients at high risk of pelvic node or high seminal vesicle involvement will need supplemental external-beam radiation therapy.

In summary, the authors’ opinion is that supplemental external-beam radiation therapy is not required in men who receive a technically adequate implant if the risk of pelvic lymph node or seminal vesicle involvement is low. Is this opinion supported by level 1 evidence? The authors’ answer is yes; we believe that the answer is not yet. In arguing this position, we will emphasize two concepts that are important for the design and interpretation of clinical trials: power and generalizability.

Key Clinical Trials

To our knowledge, three randomized trials have included brachytherapy in each arm, and Merrick and coinvestigators have been responsible for two of these. We commend the authors for designing, completing, and reporting studies that will be important contributions to the literature when the follow-up is mature. Still, the question at the heart of these two trials is, how important is external-beam radiation therapy in men treated with prostate brachytherapy?

The first trial, outlined in the authors’ Figure 7, was designed by the Seattle/Wheeling consortium, and the target accrual was 600 patients. The first published report from this study included information on only 159 analyzable patients (27% of the study population), with a median follow-up of less than 3 years.[1] At the time of this publication, only 21 patients have developed a biochemical failure (12 in the 20-Gy arm, 9 in the 44-Gy arm).

The authors used these results to support their conclusion that supplemental external-beam radiation therapy is unnecessary. It is our contention that this conclusion is premature and is based on a preliminary report with insufficient follow-up. In short, the published study is underpowered to draw meaningful conclusions. A simple power analysis indicates that the likelihood of finding a difference of the same magnitude that the authors hypothesized at the beginning of the study is approximately 20%. In other words, it is very possible that a clinically important difference between the treatment arms has not been observed because the study is, as yet, underpowered.

Additional Concerns