Objectives. In the United States, radical retropubic prostatectomy for
adenocarcinoma usually includes a staging pelvic lymphadenectomy. If
frozen section analysis of the lymph nodes fails to reveal any evidenc
e of metastases, the prostate is removed, We have previously noted tha
t as many as 56% of patients undergoing radical prostatectomy demonstr
ate rising serum prostate-specific antigen (PSA) levels by 4 years pos
toperatively. This report was designed to determine whether micrometas
tases undetectable by conventional pathologic methods could have accou
nted for these biochemical failures. Methods. A retrospective analysis
of formalin-fixed paraffin-embedded pelvic lymph node material was un
dertaken using a reverse transcription-polymerase chain reaction (RT-P
CR)-based assay designed to amplify messenger RNA from PSA. All specim
ens were obtained from a group of 57 patients with prostate cancer who
had undergone staging pelvic lymphadenectomy at the time of radical p
rostatectomy, and whose long-term follow-up was known. Results. Althou
gh all of these nodes appeared to be free of tumor by conventional pat
hologic methods, a RT-PCR assay was used to identify evidence of prost
ate metastases in 44% of evaluable samples. Of these, 14 of 16 went on
to manifest rising serum PSA values by 5 years postoperatively. Concl
usions. These results suggest that molecular staging of pelvic lymph n
odes prior to planned therapy for clinically organ-confined prostate c
ancer may better distinguish between patients with local disease and t
hose for whom local therapy alone will not be curative, To our knowled
ge, this is the first large-scale retrospective gene expression study
published.