Molecular load of pathologically occult metastases in pelvic lymph nodes is an independent prognostic marker of biochemical failure after localized prostate cancer treatment.
OBJECTIVE
Thirty percent of patients treated with curative intent for localized prostate cancer (PC) experience biochemical recurrence (BCR) with rising serum prostate-specific antigen (sPSA), and of these, approximately 50% succumb to progressive disease. More discriminatory staging procedures are needed to identify occult micrometastases that spawn BCR.


METHODS
PSA mRNA copies in pathologically normal pelvic lymph nodes (N0-PLN) from 341 localized PC patients were quantified by real-time reverse-transcriptase polymerase chain reaction. Based on comparisons with normal lymph nodes and PLN with metastases and on normalization to 5 x 10(6) glyceraldehyde-3'-phosphate dehydrogenase mRNA copies, normalized PSA copies (PSA-N) and a threshold of PSA-N 100 or more were selected for continuous and categorical multivariate analyses of biochemical failure-free survival (BFFS) compared with established risk factors.


RESULTS
At median follow-up of 4 years, the BFFS of patients with PSA-N 100 or more versus PSA-N less than 100 was 55% and 77% (P = .0002), respectively. The effect was greatest for sPSA greater than 20 ng/mL, 25% versus 60% (P = .014), Gleason score 8 or higher, 21% versus 66% (P = .0002), stage T3c, 18% versus 64% (P = .001), and high-risk group (50% v 72%; P = .05). By continuous analysis PSA-N was an independent prognostic marker for BCR (P = .049) with a hazard ratio of 1.25 (95% CI, 1.001 to 1.57). By categorical analysis, PSA-N 100 or more was an independent variable (P = .021) with a relative risk of 1.98 (95% CI, 1.11 to 3.55) for BCR compared with PSA-N less than 100.


CONCLUSIONS
PSA-N 100 or more is a new, independent molecular staging criterion for localized PC that identifies high-risk group patients with clinically relevant occult micrometastases in N0-PLN, who may benefit from additional therapy to prevent BCR.
Ferrari
Anna C
AC
New York University Cancer Institute, New York University Medical School, 160 E 34th St, 8th Floor, New York, NY 10016, USA. anna.ferrari@nyumc.org
Stone
Nelson N
NN
Kurek
Ralf
R
Mulligan
Elizabeth
E
McGregor
Roy
R
Stock
Richard
R
Unger
Pamela
P
Tunn
Ulf
U
Kaisary
Amir
A
Droller
Michael
M
Hall
Simon
S
Renneberg
Heiner
H
Livak
Kenneth J
KJ
Gallagher
Robert E
RE
Mandeli
John
J
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen