Comparing Radical Prostatectomy and Brachytherapy for Localized Prostate Cancer

September 1, 2004

There are two problems with thepaper by Quaranta et al, neitherof which can be overcomewith discussion or sophistry. The firstconcerns the criteria used to determinewhether a report would be includedin this analysis. Specifically,any series with a median follow-up ofonly 3 years was included if it alsomet the other inclusion criteria. Thisis simply inadequate, as there is greatconsensus that studies with 3-year follow-up miss many recurrences. Thesecond problem with the paper is thedefinition of recurrence. The AmericanSociety for Therapeutic Radiologyand Oncology (ASTRO) criteriaused by the authors has proven inferiorto using a cutoff of 0.2 ng/mL forprostate-specific antigen (PSA) nadirfollowing brachytherapy. The inaccuracyin using ASTRO criteria fordetermining cure by brachytherapy isparticularly pronounced in series withshort follow-up such as the 3-yearmedian follow-up criterion used inthis paper.

There are two problems with thepaper by Quaranta et al, neitherof which can be overcomewith discussion or sophistry. The firstconcerns the criteria used to determinewhether a report would be includedin this analysis. Specifically,any series with a median follow-up ofonly 3 years was included if it alsomet the other inclusion criteria. Thisis simply inadequate, as there is greatconsensus that studies with 3-year follow-up miss many recurrences. Thesecond problem with the paper is thedefinition of recurrence. The AmericanSociety for Therapeutic Radiologyand Oncology (ASTRO) criteriaused by the authors has proven inferiorto using a cutoff of 0.2 ng/mL forprostate-specific antigen (PSA) nadirfollowing brachytherapy. The inaccuracyin using ASTRO criteria fordetermining cure by brachytherapy isparticularly pronounced in series withshort follow-up such as the 3-yearmedian follow-up criterion used inthis paper.These errors in study design makethe conclusions of the study invalid.This is unfortunate indeed since thereappear to be significant improvementsin brachytherapy in recent years makingthis a much more attractive optionfor many patients with prostatecancer. This approach to overstatingthe results of brachytherapy substantiallyundermines the legitimate goalof understanding the role of modernbrachytherapy in the treatment ofprostate cancer. Simply stated, evenif the conclusions of this paper aretrue, this paper does not support theconclusions due to deficiencies instudy design.Definition of Recurrence
In an important paper not referencedin the Quaranta article, Critzargues forcefully for freedom fromprostate cancer following brachytherapyto be defined as a PSA of 0.2 ng/mLor less.[1] This report included 591men with stage T1-2, Nx prostate cancertreated between 1992 and 1996by transperineal implantation of iodine-125 followed by external-beamirradiation. Among these 591 patients,only 65 had recurrence by ASTROcriteria, whereas 93 had recurrenceby a PSA cutoff of 0.2 ng/mL, andthis difference was highly statisticallysignificant (P = .001).Critz showed that "a substantial differencein treatment results after brachytherapyfor prostate cancer is achievedsimply by changing the definition ofdisease freedom." Furthermore, "a multivariateanalysis of factors related todisease freedom revealed that the definitionof disease-free status used tocalculate disease-free survival rate isas significant as pretreatment PSA orGleason score."Length of Follow-up
The criterion of at least 3 years ofmedian follow-up used by the authorsis not sufficient for analysis of eithersurgery or radiation. Attention to thisdetail is particularly important in reportingbrachytherapy results becauseof previous reports showing continuedfailure to control disease between10 and 15 years following therapy.[2]While this paper reports an outdatedmethod of seed implantation (freehandwithout ultrasound guidance), itteaches an important lesson about usingshort-term results when comparingvarious treatments for prostatecancer. Even at 10 years' follow-up,the data indicated that seeds were comparableto surgery, and only after 10years did the real differences becomeapparent. In modern series with accuratePSA data, it is also clear that 3years is still inadequate follow-up forbrachytherapy.In another paper not cited by theauthors, Critz clearly shows that by 36 months, only 70% of men whowill ultimately achieve a PSA nadirof 0.2 ng/mL or less have in factachieved this nadir.[3] The results areeven worse for men who experience aPSA bounce, among whom only 40%of patients ultimately destined toachieve a PSA nadir of 0.2 ng/mL orless will have achieved this low PSA.While these studies neither supportnor refute the authors' conclusions,they both document the inadequacyof 36 months' follow-up. This is thereforea second error in study design.Conclusions
In summary, the Quaranta paper iscritically flawed in design, makingthe conclusion that "prostate brachytherapyappears to be at leastequivalent in outcome to radical prostatectomyfor all risk groups" unwarranted.While it is conceivable thatsuch a determination may be validlymade at some point in the future or byothers applying a more rigorous studydesign, this paper cannot legitimatelysupport this conclusion.

Disclosures:

The authors have nosignificant financial interest or other relationshipwith the manufacturers of any products or providersof any service mentioned in this article.

References:

1.

Critz FA: A standard definition of diseasefreedom is needed for prostate cancer: Undetectableprostate specific antigen compared withthe American Society of Therapeutic Radiologyand Oncology consensus definition. J Urol167:1310-1313, 2002.

2.

Zelefsky MJ, Whitmore WF: Long-termresults of retropubic permanent 125 iodine implantationof the prostate for clinically localizedprostatic cancer. J Urol 158:23-29, 1997.

3.

Critz FA: Time to achieve a prostate specificantigen nadir of 0.2 ng/ml after simultaneousirradiation for prostate cancer. J Urol168:2434-2438, 2002.