EDITORIAL COMMENT

The optimum treatment of a man with a positive margin followingradical prostatectomy remains obscure due to a number of factors,most importantly the recognition that such a pathological findingmay not represent failure to eradicate the neoplasm. Alternatively,any cancer cells left behind may not have a significant clinicalimpact. Thus, clinicians are faced with a dilemma in answering thesimple patient question; “Doctor, did you get it all?”

The authors have created a decision analysis model to try and deter-mine the preferred treatment of such patients. They proposed the 3options of surveillance, immediate adjuvant (prophylactic) radiationand delayed therapeutic radiation given after PSA becomes detectable.The authors assigned utilities for the potential outcomes. They usedfigures from the literature and experience from their institution asmodel inputs.

Using the published literature results, the decision model recom-mends an initial surveillance of such patients. With testing of the modelwith various pathological parameters and PSA level, however, the au-thors concluded that the initial adjuvant radiation would be beneficialto those men with low to intermediate grade disease without evidence ofseminal vesicle invasion and multiple positive margins. The authors areto be applauded for performing such an analysis. Potentially the modelwould help in the management of the large cohort of men with suchadverse pathological findings. However, before this model is widelyapplied I believe several cautions should be raised.

We all recognize that there has been a significant stage migration inthe presentation of prostate cancer during the last several years, pri-marily from the use of PSA testing and resulting clinical T1c disease.The majority of articles used for the present study were published in themid 1990s when patients were diagnosed and treated before wide-spread PSA testing was used. We can assume that these historicalseries were comprised of patients with more significant disease thanthose contemporarily recognized. Thus, extrapolation to present pa-tients may not be appropriate. Median followup in this series is 46months after surgery. Most of the series from the literature using themodel had only 3 years of followup. The long-term affect on biochemical-free survival following adjuvant radiation may not be fully apprised.

The observation (data not provided) that there was no difference inoutcome when men with Gleason grade 4 or 5 (score 7 or greater)were compared to patients not exhibiting this well recognized ad-verse histological finding is surprising. The abundant data fromStanford University1 and elsewhere would call into question thisfinding. The extraordinary high degree of concordance between thevarious assignment of utilities associated with various outcomes bythe authors suggests an intra-institution bias effect. It would beimperative before this model is applied on a wider basis to have otherexperts provide their own utilities to determine the risk-to-benefitratio for adjuvant therapy.

All of us who treat men with prostate cancer would certainlywelcome a definitive answer to the question of how to treat thepositive margin. While I believe this study provides an interestinganalytic approach to this dilemma, I am afraid that we will have towait for the results of the ongoing randomized clinical trials to reallyknow what is best for our patients.

Michael K. BrawerNorthwest Prostate InstituteSeattle, Washington

1. Stamey, T. A., McNeal, J. E., Yemoto, C. M. et al: Biologicaldeterminants of cancer progression in men with prostate can-cer. JAMA, 281: 1395, 1999

REPLY BY AUTHORS

Most studies to date examining the impact of margin status ondisease recurrence after radical prostatectomy have demonstratedthat a positive margin has an adverse impact on outcome (references7, 9, 10 and 27 in article).1, 2 We agree that such a finding does notpredict disease recurrence in all patients. Thus, a patient who is toldhe has a positive margin is faced with the question, “What, if any-thing, should I do now?”

The purpose of our study was to provide a framework by whichclinicians and patients can address this difficult question. Resultsfrom prospective, randomized trials addressing this question are notyet available. Therefore, novel methods of data analysis may helpclinicians and patients. The considerable limitations to the dataused to construct our model were addressed in the discussion. Thestudies chosen for inclusion represent the best data currently avail-able. The subjectivity and potential intra-institutional bias of theutility values were also addressed in the discussion. These utilityvalues were assigned to the decision tree only to illustrate how themodel performs in a given situation. For the decision model to beuseful for a particular patient with a positive margin, that patientmust assign his own personal utility values to each outcome of thedecision tree and determine the experience of his treating physicianwith respect to the probabilities associated with each outcome.Therefore, the model may be helpful for individual patients and theirphysicians.

It was our hypothesis that patients most likely to benefit frompostoperative radiation for a positive surgical margin were thosewith recurrent or persistent local rather than distant disease. Thus,the model was not tested for patients with high grade (Gleason 8 to10) disease. What our data do show is that for men with well tomoderately differentiated disease, defined as Gleason score less than8 in the article, the decision model recommended immediate adju-vant radiation over initial surveillance. When the data were reana-lyzed with Gleason score less than 7, defined as well to moderatelydifferentiated disease, similar results were obtained from the deci-sion model. We only analyzed the effect of total Gleason score and notindividual Gleason patterns. Moreover, such results do not provide acomparison of outcome based on Gleason grade but they determinethe outcome of the decision model when restricting analysis to spe-cific patient subgroups. We and others await the publication ofrandomized trials and more contemporary information addressingthis important issue.

1. Blute, M. L., Bostwick, D. G., Bergstralh, E. J. et al: Anatomicsite-specific positive margins in organ-confined prostate can-cer and its impact on outcome after radical prostatectomy.Urology, 50: 733, 1997

2. Grossfeld, G. D., Chang, J. J., Broering, J. M. et al: Impact ofpositive surgical margins on prostate cancer recurrence anduse of secondary cancer treatment: data from the CapSuredatabase. J Urol, 163: 1171, 2000

DECISION ANALYSIS FOR MANAGEMENT OF POSITIVE MARGIN AFTER PROSTATECTOMY100