Molecular determination of surgical margins using fossa biopsies at radical prostatectomy

Purpose: Status of the surgical margins after radical prostatectomy is a ke y factor for predicting postoperative outcome. Current methods used to dete rmine mat-gin status are tedious, costly and vary among institutions. Sensi tive and inexpensive detection of prostate cells in the circulation of pati ents with prostate cancer has been achieved using reverse transcriptase (RT ) polymerase chain reaction (PCR) for prostate specific antigen and prostat e specific membrane antigen. Therefore, we designed and tested a novel and objective molecular assay for assessing surgical margins at radical prostat ectomy based on the detection of prostate specific markers using RT-PCR. We also compared this assay to standard pathological examination. Materials and Methods: A total of 30 consecutive patients with local prosta te cancer underwent radical prostatectomy. At the completion of gland excis ion 5 biopsies of the prostatic fossa were obtained for histopathological a nd molecular analysis. We performed TCT-PGR analysis for prostate specific antigen and prostate specific membrane antigen messenger ribonucleic acid i n these biopsy specimens, and compared the results with pathological stage. Men free of prostate cancer who underwent radical cystoprostatectomy for b ladder cancer or abdominoperineal resection for rectal cancer served as con trols. Results: There were positive molecular margins in all patients with positiv e margins and/or extracapsular extension. No controls had a positive molecu lar assay. In 4 of 16 patients (25%) histopathological evaluation revealed organ confined disease but: biopsies were positive by the molecular assay, including those in 2 (50%) who had been treated with neoadjuvant hormonal t herapy before surgery because of a higher estimated risk of extracapsular d isease. Results in 4 cases were uninformative. Conclusions: Our results with an objective molecular assay aimed at assessi ng surgical margins after radical prostatectomy reveal an excellent correla tion with conventional pathological analysis. In addition, molecular assess ment of the prostatic fossa identifies patients in whom extracapsular disea se may have been unidentified by conventional pathological examination. In addition, this assay yields clues to why neoadjuvant hormonal treatment bef ore radical prostatectomy does not seem to decrease the biochemical failure rate in these patients. Larger studies with longer followup are required t o determine the prognostic significance of these positive molecular margins .