Skip to main content
SpringerLink
Log in

PSA doubling time for prediction of [11C]choline PET/CT findings in prostate cancer patients with biochemical failure after radical prostatectomy

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Previous studies have shown that the positive detection rate of [11C]choline positron emission tomography/computed tomography (PET/CT) depends on prostate-specific antigen (PSA) plasma levels. This study compared PSA levels and PSA doubling time (PSADT) to predict [11C]choline PET/CT findings.

Methods

PSADT was retrospectively calculated in 170 prostate cancer (PCa) patients with biochemical failure after radical prostatectomy who underwent [11C]choline PET/CT. PSADT was calculated as PSADT = ln2/m, where m is the slope of the linear regression line of the natural log of PSA values. At least three PSA measurements were used (median: 4; range: 3–16), separated by at least 3 months, each with a minimum increase of 0.20 ng/ml. PET/CT findings were validated using criteria based on histological analysis and clinical and imaging data. Statistical analysis was performed using the t test, chi-square test, analysis of variance and binary logistic regression. Regression-based coefficients were used to develop a nomogram predicting the probability of positive [11C]choline PET/CT and 200 bootstrap resamples were used for internal validation.

Results

The median PSA was 1.25 ng/ml (range: 0.23–48.6 ng/ml), and the median PSADT was 7.0 months (range: 0.97–45.3 months). [11C]choline PET/CT was positive in 75 of 170 patients (44%). PET/CT findings were validated using histological criteria (11%) and clinical and imaging criteria (89%). The overall accuracy of [11C]choline PET/CT was 88%. Multivariate logistic regression showed that high PSA and short PSADT were significant (p < 0.05) predictors of positive [11C]choline PET/CT [PSA: odds ratio (OR) = 1.43; 95% confidence interval (CI): 1.15–1.78; PSADT: OR = 1.12; 95% CI: 1.04–1.21]. The percentage of patients with positive [11C]choline PET/CT was 27% for PSADT >6 months, 61% for PSADT between 3 and 6 months and 81% for PSADT <3 months. The percentage of patients who displayed pathological [11C]choline uptake in the skeleton significantly increased (p < 0.05) from 3% for PSADT >6 months to 52% for PSADT <3 months. Conversely, patients who displayed pathological [11C]choline uptake in the prostatectomy bed were 0% for PSADT <3 months and 17% for PSADT >6 months (p < 0.05). A nomogram based on age, PSA, PSADT, time to trigger PSA, Gleason score, pathological stage and androgen deprivation therapy demonstrated bootstrap-corrected predictive accuracy of 81%.

Conclusion

Like PSA, PSADT is an independent predictor of [11C]choline PET/CT. [11C]choline PET/CT is very sensitive to PCa tumour growth, as reflected by PSA kinetics. PSADT should be taken into account by physicians when referring PCa patients for [11C]choline PET/CT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Amling CL, Blute ML, Bergstralh EJ, Seay TM, Slezak J, Zincke H. Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years. J Urol 2000;164:101–5.

    Article  PubMed  CAS  Google Scholar 

  2. Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 2003;169:517–23.

    Article  PubMed  Google Scholar 

  3. de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. 11C-choline positron emission tomography for the evaluation after treatment of localized prostate cancer. Eur Urol 2003;44:32–8.

    Article  PubMed  Google Scholar 

  4. Picchio M, Messa C, Landoni C, Gianolli L, Sironi S, Brioschi M, et al. Value of [11C]choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F]fluorodeoxyglucose-positron emission tomography. J Urol 2003;169:1337–40.

    Article  PubMed  CAS  Google Scholar 

  5. Heinisch M, Dirisamer A, Loidl W, Stoiber F, Gruy B, Haim S, et al. Positron emission tomography/computed tomography with F-18-fluorocholine for restaging of prostate cancer patients: meaningful at PSA < 5 ng/ml? Mol Imaging Biol.2006;8:43–8.

    Article  PubMed  Google Scholar 

  6. Husarik DB, Miralbell R, Dubs M, John H, Giger OT, Gelet A, et al. Evaluation of [(18)F]-choline PET/CT for staging and restaging of prostate cancer. Eur J Nucl Med Mol Imaging 2008;35:253–63.

    Article  PubMed  Google Scholar 

  7. Krause BJ, Souvatzoglou M, Tuncel M, Herrmann K, Buck AK, Praus C, et al. The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer. Eur J Nucl Med Mol Imaging 2008;35:18–23.

    Article  PubMed  CAS  Google Scholar 

  8. Castellucci P, Fuccio C, Nanni C, Santi I, Rizzello A, Lodi F, et al. Influence of trigger PSA and PSA kinetics on 11C-choline PET/CT detection rate in patients with biochemical relapse after radical prostatectomy. J Nucl Med 2009;50:1394–400.

    Article  PubMed  CAS  Google Scholar 

  9. Giovacchini G, Picchio M, Coradeschi E, Bettinardi V, Gianolli L, Scattoni V, et al. Predictive factors of [(11)C]choline PET/CT in patients with biochemical failure after radical prostatectomy. Eur J Nucl Med Mol Imaging 2010;37:301–9.

    Article  PubMed  Google Scholar 

  10. D’Amico AV, Moul JW, Carroll PR, Sun L, Lubeck D, Chen MH. Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Natl Cancer Inst 2003;95:1376–83.

    PubMed  Google Scholar 

  11. Arlen PM, Bianco F, Dahut WL, D’Amico A, Figg WD, Freedland SJ, et al. Prostate Specific Antigen Working Group guidelines on prostate specific antigen doubling time. J Urol 2008;179:2181–5.

    Article  PubMed  Google Scholar 

  12. Bettinardi V, Mancosu P, Danna M, Giovacchini G, Landoni C, Picchio M, et al. Two-dimensional vs three-dimensional imaging in whole body oncologic PET/CT: a Discovery-STE phantom and patient study. Q J Nucl Med Mol Imaging 2007;51:214–23.

    PubMed  CAS  Google Scholar 

  13. Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 1998;39:990–5.

    PubMed  CAS  Google Scholar 

  14. Taylor SH, Merriman KW, Spiess PE, Pisters L. Inadequacies of the current American Joint Committee on cancer staging system for prostate cancer. Cancer 2006;106:559–65.

    Article  PubMed  Google Scholar 

  15. Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, Dorey FJ, Walsh PC, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 2005;294:433–9.

    Article  PubMed  CAS  Google Scholar 

  16. Hosmer DW, Hjort NL. Goodness-of-fit processes for logistic regression: simulation results. Stat Med 2002;21:2723–38.

    Article  PubMed  Google Scholar 

  17. Partin AW, Pearson JD, Landis PK, Carter HB, Pound CR, Clemens JQ, et al. Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases. Urology 1994;43:649–59.

    Article  PubMed  CAS  Google Scholar 

  18. Kattan MW, Wheeler TM, Scardino PT. Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol 1999;17:1499–507.

    PubMed  CAS  Google Scholar 

  19. Cher ML, Bianco Jr FJ, Lam JS, Davis LP, Grignon DJ, Sakr WA, et al. Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy. J Urol 1998;160:1387–91.

    Article  PubMed  CAS  Google Scholar 

  20. Silverman JM, Krebs TL. MR imaging evaluation with a transrectal surface coil of local recurrence of prostatic cancer in men who have undergone radical prostatectomy. AJR Am J Roentgenol 1997;168:379–85.

    PubMed  CAS  Google Scholar 

  21. Kane CJ, Amling CL, Johnstone PA, Pak N, Lance RS, Thrasher JB, et al. Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy. Urology 2003;61:607–11.

    Article  PubMed  Google Scholar 

  22. Schmid DT, John H, Zweifel R, Cservenyak T, Westera G, Goerres GW, et al. Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology 2005;235:623–8.

    Article  PubMed  Google Scholar 

  23. Reske SN, Blumstein NM, Glatting G. [11C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy. Eur J Nucl Med Mol Imaging 2008;35:9–17.

    Article  PubMed  Google Scholar 

  24. Carter HB, Morrell CH, Pearson JD, Brant LJ, Plato CC, Metter EJ, et al. Estimation of prostatic growth using serial prostate-specific antigen measurements in men with and without prostate disease. Cancer Res 1992;52:3323–8.

    PubMed  CAS  Google Scholar 

  25. D’Amico AV, Hanks GE. Linear regressive analysis using prostate-specific antigen doubling time for predicting tumor biology and clinical outcome in prostate cancer. Cancer 1993;72:2638–43.

    Article  PubMed  Google Scholar 

  26. Patel A, Dorey F, Franklin J, deKernion JB. Recurrence patterns after radical retropubic prostatectomy: clinical usefulness of prostate specific antigen doubling times and log slope prostate specific antigen. J Urol 1997;158:1441–5.

    Article  PubMed  CAS  Google Scholar 

  27. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591–7.

    Article  PubMed  CAS  Google Scholar 

  28. Dotan ZA, Bianco Jr FJ, Rabbani F, Eastham JA, Fearn P, Scher HI, et al. Pattern of prostate-specific antigen (PSA) failure dictates the probability of a positive bone scan in patients with an increasing PSA after radical prostatectomy. J Clin Oncol 2005;23:1962–8.

    Article  PubMed  Google Scholar 

  29. Zhou P, Chen MH, McLeod D, Carroll PR, Moul JW, D’Amico AV. Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Clin Oncol 2005;23:6992–8.

    Article  PubMed  Google Scholar 

  30. D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 2004;351:125–35.

    Article  PubMed  Google Scholar 

  31. Lee WR, Hanks GE, Hanlon A. Increasing prostate-specific antigen profile following definitive radiation therapy for localized prostate cancer: clinical observations. J Clin Oncol 1997;15:230–8.

    PubMed  CAS  Google Scholar 

  32. Sartor CI, Strawderman MH, Lin XH, Kish KE, McLaughlin PW, Sandler HM. Rate of PSA rise predicts metastatic versus local recurrence after definitive radiotherapy. Int J Radiat Oncol Biol Phys 1997;38:941–7.

    PubMed  CAS  Google Scholar 

  33. Zelefsky MJ, Ben-Porat L, Scher HI, Chan HM, Fearn PA, Fuks ZY, et al. Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer. J Clin Oncol 2005;23:826–31.

    Article  PubMed  Google Scholar 

  34. Sandler HM, Dunn RL, McLaughlin PW, Hayman JA, Sullivan MA, Taylor JM. Overall survival after prostate-specific-antigen-detected recurrence following conformal radiation therapy. Int J Radiat Oncol Biol Phys 2000;48:629–33.

    PubMed  CAS  Google Scholar 

  35. Stephenson AJ, Scardino PT, Kattan MW, Pisansky TM, Slawin KM, Klein EA, et al. Predicting the outcome of salvage radiation therapy for recurrent prostate cancer after radical prostatectomy. J Clin Oncol 2007;25:2035–41.

    Article  PubMed  Google Scholar 

  36. Oudard S, Banu E, Scotte F, Banu A, Medioni J, Beuzeboc P, et al. Prostate-specific antigen doubling time before onset of chemotherapy as a predictor of survival for hormone-refractory prostate cancer patients. Ann Oncol 2007;18:1828–33.

    Article  PubMed  CAS  Google Scholar 

  37. Perlmutter MA, Lepor H. Prostate-specific antigen doubling time is a reliable predictor of imageable metastases in men with biochemical recurrence after radical retropubic prostatectomy. Urology 2008;71:501–5.

    Article  PubMed  Google Scholar 

  38. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889;1:571–3.

    Article  Google Scholar 

  39. Ghossein RA, Scher HI, Gerald WL, Kelly WK, Curley T, Amsterdam A, et al. Detection of circulating tumor cells in patients with localized and metastatic prostatic carcinoma: clinical implications. J Clin Oncol 1995;13:1195–200.

    PubMed  CAS  Google Scholar 

  40. Lilja H, O’Brien F. Can PSA velocity predict risk of death in men with prostate cancer? Nat Clin Pract Urol 2007;4:410–1.

    Article  PubMed  Google Scholar 

  41. O’Brien MF, Cronin AM, Fearn PA, Smith B, Stasi J, Guillonneau B, et al. Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy. J Clin Oncol 2009;27:3591–7.

    Article  PubMed  CAS  Google Scholar 

  42. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 2001;58:843–8.

    Article  PubMed  CAS  Google Scholar 

  43. D’Amico AV, Cote K, Loffredo M, Renshaw AA, Schultz D. Determinants of prostate cancer-specific survival after radiation therapy for patients with clinically localized prostate cancer. J Clin Oncol 2002;20:4567–73.

    Article  PubMed  Google Scholar 

  44. Briganti A, Chun FK, Salonia A, Zanni G, Scattoni V, Valiquette L, et al. Validation of a nomogram predicting the probability of lymph node invasion among patients undergoing radical prostatectomy and an extended pelvic lymphadenectomy. Eur Urol 2006;49:1019–26.

    Article  PubMed  Google Scholar 

  45. Lee AK, D’Amico AV. Using prostate-specific antigen doubling time in clinical practice. BJU Int 2007;100:243–4.

    Article  PubMed  Google Scholar 

  46. Cimitan M, Bortolus R, Morassut S, Canzonieri V, Garbeglio A, Baresic T, et al. [18F]fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients. Eur J Nucl Med Mol Imaging 2006;33:1387–98.

    Article  PubMed  Google Scholar 

  47. Kotzerke J, Volkmer BG, Glatting G, van den Hoff J, Gschwend JE, Messer P, et al. Intraindividual comparison of [11C]acetate and [11C]choline PET for detection of metastases of prostate cancer. Nuklearmedizin 2003;42:25–30.

    PubMed  CAS  Google Scholar 

  48. Testa C, Schiavina R, Lodi R, Salizzoni E, Corti B, Farsad M, et al. Prostate cancer: sextant localization with MR imaging, MR spectroscopy, and 11C-choline PET/CT. Radiology 2007;244:797–806.

    Article  PubMed  Google Scholar 

  49. Scattoni V, Picchio M, Suardi N, Messa C, Freschi M, Roscigno M, et al. Detection of lymph-node metastases with integrated [11C]choline PET/CT in patients with PSA failure after radical retropubic prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. Eur Urol 2007;52:423–9.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

We would like to thank Andrea Gallina, M.D., for his excellent support in the statistical analysis.

Author information

Authors and Affiliations

  1. Center for Molecular Bioimaging, University of Milano-Bicocca, Milan, Italy

    Giampiero Giovacchini, Rita Garcia Parra & Cristina Messa

  2. Department of Nuclear Medicine, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy

    Maria Picchio & Luigi Gianolli

  3. Department of Urology, San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy

    Vincenzo Scattoni, Alberto Briganti & Francesco Montorsi

  4. Institute for Bioimaging and Molecular Physiology, National Research Council, Milan, Italy

    Cristina Messa

  5. Department of Nuclear Medicine, San Gerardo Hospital, Monza, Italy

    Cristina Messa

Authors
  1. Giampiero Giovacchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Picchio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincenzo Scattoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rita Garcia Parra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alberto Briganti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luigi Gianolli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francesco Montorsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cristina Messa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Picchio.

Electronic Supplementary Material

ESM 1

(DOC 53 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giovacchini, G., Picchio, M., Scattoni, V. et al. PSA doubling time for prediction of [11C]choline PET/CT findings in prostate cancer patients with biochemical failure after radical prostatectomy. Eur J Nucl Med Mol Imaging 37, 1106–1116 (2010). https://doi.org/10.1007/s00259-010-1403-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-010-1403-7

Keywords

Search

Navigation