Molecular determination of surgical margins using fossa biopsies at radical prostatectomy

Status of the surgical margins after radical prostatectomy is a key factor for predicting postoperative outcome. Current methods used to determine margin status are tedious, costly and vary among institutions. Sensitive and inexpensive detection of prostate cells in the circulation of patients with prostate cancer has been achieved using reverse transcriptase (RT) polymerase chain reaction (PCR) for prostate specific antigen and prostate specific membrane antigen. Therefore, we designed and tested a novel and objective molecular assay for assessing surgical margins at radical prostatectomy based on the detection of prostate specific markers using RT-PCR. We also compared this assay to standard pathological examination.

A total of 30 consecutive patients with local prostate cancer underwent radical prostatectomy. At the completion of gland excision 5 biopsies of the prostatic fossa were obtained for histopathological and molecular analysis. We performed RT-PCR analysis for prostate specific antigen and prostate specific membrane antigen messenger ribonucleic acid in these biopsy specimens, and compared the results with pathological stage. Men free of prostate cancer who underwent radical cystoprostatectomy for bladder cancer or abdominoperineal resection for rectal cancer served as controls.

There were positive molecular margins in all patients with positive margins and/or extracapsular extension. No controls had a positive molecular 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 therapy before surgery because of a higher estimated risk of extracapsular disease. Results in 4 cases were uninformative.

Our results with an objective molecular assay aimed at assessing surgical margins after radical prostatectomy reveal an excellent correlation with conventional pathological analysis. In addition, molecular assessment of the prostatic fossa identifies patients in whom extracapsular disease may have been unidentified by conventional pathological examination. In addition, this assay yields clues to why neoadjuvant hormonal treatment before radical prostatectomy does not seem to decrease the biochemical failure rate in these patients. Larger studies with longer followup are required to determine the prognostic significance of these positive molecular margins.