Quantitative RT-PCR analysis of PSA and prostate-specific membrane antigen mRNA to detect circulating tumor cells improves recurrence-free survival nomogram prediction after radical prostatectomy

Prostate. 2012 Sep 1;72(12):1382-8. doi: 10.1002/pros.22488. Epub 2012 Jan 6.

Abstract

Background: Circulating tumor cell (CTC) analysis is a potential new biomarker in prostate cancer. We hypothesize that quantitative detection of CTCs in patients pre- and post-radical prostatectomy (RP) using quantitative TaqMan® fluorogenic RT-PCR will improve the accuracy of the Kattan nomogram to predict the probability of recurrence-free survival (RFS) post-RP.

Methods: Ninty-two patients who underwent RP between 2004 and 2009 had venous blood samples taken pre- (Day - 1) and post-operatively (Day + 7). We performed quantitative Taqman® RT-PCR to detect circulating prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) mRNA. We calculated both the logarithmic ratio of Day + 7/Day - 1 for PSA (PSAr) and PSMA (PSMAr) expression (log(Day+7/Day-1) ) and the Kattan nomogram predicted probability of disease recurrence for each patient. We then analyzed how the AUC-ROC analysis for the Kattan nomogram prediction alone (K) compared to the addition of the PSAr and PSMAr in predicting 5-year RFS.

Results: The mean age (years), PSA (ng/ml), and follow-up (mo) was 65.1, 9.13, and 72, respectively. The AUCs for K, PSAr + K, and PSMAr + K were 0.752 (95%CI 0.620-0.860), 0.830 (95%CI 0.740-0.911), and 0.837 (95%CI 0.613-0.923), respectively (P = 0.03). The Kattan 5-year PSA RFS was 75%. The actual 5-year PSA RFS survival rate was 77%.

Conclusions: Data from modern quantitative RT-PCR to detect circulating prostate-derived PSA and PSM mRNA pre- and post-RP improves the accuracy of the Kattan nomogram to predict biochemical recurrence.

MeSH terms

  • Aged
  • Antigens, Surface / blood
  • Antigens, Surface / genetics*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Disease-Free Survival
  • Follow-Up Studies
  • Glutamate Carboxypeptidase II / blood
  • Glutamate Carboxypeptidase II / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplastic Cells, Circulating / pathology*
  • Nomograms
  • Predictive Value of Tests
  • Prostate-Specific Antigen / blood*
  • Prostate-Specific Antigen / chemistry
  • Prostate-Specific Antigen / genetics*
  • Prostatectomy*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / surgery
  • RNA, Messenger* / blood
  • RNA, Messenger* / genetics
  • Real-Time Polymerase Chain Reaction / methods*
  • Recurrence

Substances

  • Antigens, Surface
  • Biomarkers, Tumor
  • RNA, Messenger
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Prostate-Specific Antigen