Reconsidering the Case for Brachytherapy Plus EBRT in High-Risk Prostate Cancer

In the article entitled "Interstitial Brachytherapy Should Be Standard of Care for Treatment of High-Risk Prostate Cancer," Merrick, Wallner, and Butler once again make the case for interstitial brachytherapy as a primary treatment for prostate cancer (see their earlier article, "Permanent Prostate Brachytherapy: Is Supplemental External-Beam Radiation Therapy Necessary?" in ONCOLOGY, April 2006).[1] This time Nathan Bittner has joined as the lead author.

The group makes many of the same points that they did 2 years ago—that extracapsular extension can be adequately treated with brachytherapy, likewise most seminal vesicle invasion that is usually proximal, and that previous brachytherapy studies reporting poor outcomes for patients in intermediate- and high-risk categories are explained by poor technique, which has been corrected over the past several years. Furthermore, they "attempt to dispel some common misconceptions about prostate brachytherapy" and "in doing so, … hope to convince the reader that brachytherapy is the best available local therapy and should be standard of care in the treatment of high-risk prostate cancer."

Finally, the authors seem to imply that brachytherapy should be the standard of care for high-risk disease, as they feel that modern data suggest that brachytherapy with supplemental external-beam radiation therapy (EBRT) produces a better cancer-free outcome compared to external-beam irradiation alone (or prostatectomy). So it seems that—at least in this instance—it is advantageous to embrace supplemental external-beam radiation, which the authors largely deemed unnecessary previously, since much of the supporting data for high-risk disease includes EBRT and sometimes hormone therapy as well. The current article is written with such conviction that it does cause one to consider the authors' proposal. Let us then more carefully examine some of the issues.

Extracapsular Extension and Seminal Vesicle Involvement

With regard to extracapsular extension, it seems reasonable to assume that adequate coverage generally may be possible with the combination of EBRT and brachytherapy if 3- to 6-mm 100% dose margins are consistently attainable with an implant, as the authors suggest. However, according to the prostatectomy-based model of Schwartz et al,[2] depending on predictive factors within the high-risk group, some patients may have tumor extension outside the 6-mm implantable limit more than half the time. An additional worry concerns the prostate base and beyond, where it is well known that dose may often be compromised with implant, and where patients with high-risk disease may have extension to the bladder neck or into and around the seminal vesicles (SV).

Although the authors report that implanting the SV is possible, they also admit that the dose distribution is "variable" and even a "formidable challenge" when it comes to the more distal SV. What consistently accurate method do we have to help us decide which patients can get by with just 45 Gy, and to exactly how much of the SV? Although Stock and colleagues show an 8-year biochemical disease-free survival (BDFS) of 83% for all high-risk patients (Table 1 of the Bittner et al article), they also report a 7-year BDFS of 67% for biopsy-confirmed SV involvement with their implant technique.[3,4] Moreover, SV involvement typically heralds a more advanced disease state that often cannot be cured by local treatment. This, of course, is the reason for applying systemic therapy, either hormonal or cytotoxic, as in the current adjuvant prostatectomy clinical trials.[5]