"Supplemental beam" and prostate brachytherapy: a simple answer to a complicated question?

I like simple answers to simple questions. When I can’t get them I’ll take (as “the next best thing”), simple answers to complex questions. Unfortunately, with regard to prostate cancer, we tend to get many complicated questions and a few complicated answers. In this issue of the “Red Journal,” Ghaly, Wallner, Merrick et al. attempt to provide a simple answer to what would seem to be a simple question (1). They attempt to answer the question: “Does supplemented beam radiation increase the morbidity of prostate brachytherapy?” They reach a simple answer: “Supplemental beam radiation appears to have little effect on morbidity.” Although they may be correct, the question may be more complicated than the answer would lead you to believe. First, an underpowered study may fail to show differences that do exist. There could be subsets of patients with increased morbidity that could be missed in a small study with a relatively short follow-up. For example, the investigators did report that in the first month there was worse rectal morbidity when “supplemental beam” was combined with Palladium 103. Thus, their conclusions that “the addition of supplemental beam had little effect on morbidity” must be viewed cautiously, because other differences in morbidity may yet become apparent over time. The point is the study is not over. Ignoring for the moment that longer follow-up and more patients are needed to definitively answer the question of morbidity, this is still a very complicated matter. Two major theories exist as to why supplemental external beam irradiation (EBRT) might be beneficial. First, for those patients unfortunate enough to have microscopic extracapsular extension, adding external beam might allow better coverage of disease. However, a number of investigators have shown the vast majority of such patients will have adequate coverage of their disease with a generous implant margin (2). Second, “supplemental beam” might compensate for “cold spots” (places where seeds are supposed to be but aren’t, resulting in underdosing). Having seen the generous margins used by these investigators and their excellent coverage, they will probably correctly conclude that, in their hands, there is no clinical benefit to the use of “supplemental beam” in low-risk patients. Similarly, these investigators know how to avoid the rectum during the implant and, because most of the dose is delivered via the implant, I’m not surprised that large differences are not yet obvious. Are there additional potential benefits or morbidity associated with “supplemental beam” that they might not be able to detect with these studies? I say “Yes!” In this analysis, these investigators use the term “supplemental beam” to refer to patients receiving external beam irradiation designed to cover the prostate and seminal vesicles with a 2.0 cm margin and 1.0 cm posteriorly. For patients with only periprostatic or periseminal vesicle lymph nodes, the field described might be adequate, but such patients are relatively uncommon (3). Might the conclusions be different if supplemental beam consisted of whole pelvic radiotherapy (WPRT)? Might the conclusions be different still if neoadjuvant hormonal therapy was added to WPRT? What if there was evidence of an important biologic interaction when WPRT is combined with neoadjuvant hormonal therapy (NHT)? What if this interaction could only be shown in patients with a risk of positive lymph nodes of 15%? If this were true, then these investigators may not be answering the supplemental beam question for the patients for whom it might be most important! In fact, there are excellent data to suggest that there is an important biologic interaction between WPRT and NHT (4). This observation complicates the issue of supplemental beam or no supplemental beam. An important biologic interaction between hormonal therapy and radiotherapy might be missed in their study, because they excluded the lymph nodes. If WPRT was used, then a larger portion of rectum might be put at risk, and conclusions about the morbidity of the combined approach might also change. Not only does Radiation Therapy Oncology Group (RTOG) 9413 demonstrate a benefit in terms of progression-free