Comparing Radical Prostatectomy and Brachytherapy for Localized Prostate Cancer

There are two problems with the paper by Quaranta et al, neither of which can be overcome with discussion or sophistry. The first concerns the criteria used to determine whether a report would be included in this analysis. Specifically, any series with a median follow-up of only 3 years was included if it also met the other inclusion criteria. This is simply inadequate, as there is great consensus that studies with 3-year follow- up miss many recurrences. The second problem with the paper is the definition of recurrence. The American Society for Therapeutic Radiology and Oncology (ASTRO) criteria used by the authors has proven inferior to using a cutoff of 0.2 ng/mL for prostate-specific antigen (PSA) nadir following brachytherapy. The inaccuracy in using ASTRO criteria for determining cure by brachytherapy is particularly pronounced in series with short follow-up such as the 3-year median follow-up criterion used in this paper. These errors in study design make the conclusions of the study invalid. This is unfortunate indeed since there appear to be significant improvements in brachytherapy in recent years making this a much more attractive option for many patients with prostate cancer. This approach to overstating the results of brachytherapy substantially undermines the legitimate goal of understanding the role of modern brachytherapy in the treatment of prostate cancer. Simply stated, even if the conclusions of this paper are true, this paper does not support the conclusions due to deficiencies in study design. Definition of Recurrence
In an important paper not referenced in the Quaranta article, Critz argues forcefully for freedom from prostate cancer following brachytherapy to be defined as a PSA of 0.2 ng/mL or less.[1] This report included 591 men with stage T1-2, Nx prostate cancer treated between 1992 and 1996 by transperineal implantation of iodine(Drug information on iodine)- 125 followed by external-beam irradiation. Among these 591 patients, only 65 had recurrence by ASTRO criteria, whereas 93 had recurrence by a PSA cutoff of 0.2 ng/mL, and this difference was highly statistically significant (P = .001). Critz showed that "a substantial difference in treatment results after brachytherapy for prostate cancer is achieved simply by changing the definition of disease freedom." Furthermore, "a multivariate analysis of factors related to disease freedom revealed that the definition of disease-free status used to calculate disease-free survival rate is as significant as pretreatment PSA or Gleason score." Length of Follow-up
The criterion of at least 3 years of median follow-up used by the authors is not sufficient for analysis of either surgery or radiation. Attention to this detail is particularly important in reporting brachytherapy results because of previous reports showing continued failure to control disease between 10 and 15 years following therapy.[2] While this paper reports an outdated method of seed implantation (freehand without ultrasound guidance), it teaches an important lesson about using short-term results when comparing various treatments for prostate cancer. Even at 10 years' follow-up, the data indicated that seeds were comparable to surgery, and only after 10 years did the real differences become apparent. In modern series with accurate PSA data, it is also clear that 3 years is still inadequate follow-up for brachytherapy. In another paper not cited by the authors, Critz clearly shows that by 36 months, only 70% of men who will ultimately achieve a PSA nadir of 0.2 ng/mL or less have in fact achieved this nadir.[3] The results are even worse for men who experience a PSA bounce, among whom only 40% of patients ultimately destined to achieve a PSA nadir of 0.2 ng/mL or less will have achieved this low PSA. While these studies neither support nor refute the authors' conclusions, they both document the inadequacy of 36 months' follow-up. This is therefore a second error in study design. Conclusions
In summary, the Quaranta paper is critically flawed in design, making the conclusion that "prostate brachytherapy appears to be at least equivalent in outcome to radical prostatectomy for all risk groups" unwarranted. While it is conceivable that such a determination may be validly made at some point in the future or by others applying a more rigorous study design, this paper cannot legitimately support this conclusion.