Yonsei Med J.  2011 Jan;52(1):74-80. 10.3349/ymj.2011.52.1.74.

Nomogram to Predict Insignificant Prostate Cancer at Radical Prostatectomy in Korean Men: A Multi-Center Study

• Chung JS
• Choi HY
• Song HR
• Byun SS
• Seo SI
• Song C
• Cho JS
• Lee SE
• Ahn H
• Lee ES
• Hwang TK
• Kim WJ
• Chung MK
• Jung TY
• Yu HS
• Choi YD

• KMID: 1106440
• DOI: http://doi.org/10.3349/ymj.2011.52.1.74

Abstract

PURPOSE
Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC.
MATERIALS AND METHODS
The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort.
RESULTS
Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827.
CONCLUSION
Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are considered.

Keyword

Prostatic neoplasms; nomograms; insignificant

MeSH Terms

Aged
Asian Continental Ancestry Group
Humans
Logistic Models
Male
Middle Aged
*Nomograms
Prostatectomy
Prostatic Neoplasms/*diagnosis/surgery

Figure

• 

  Fig. 1 (A) Nomogram for predicting IPC in localized prostate cancer. Find the position of each variable on the corresponding axis, draw a line to the 'points' axis for the number of points, add the points from all the variables together, and draw a line from the 'total points' axis to determine the IPC probabilities at the bottom. (B) Calibration curves of preoperative nomogram in internal validation cohort. The x-axis is the predicted probability and the y-axis is the actual probability of IPC from the nomogram. The dashed line represents the ideal calibration curve for the nomogram (i.e., predicted probability completely corresponds with actual probability). The apparent accuracy without correction for over fit and bootstrap-corrected performance of our nomogram were represented by the dotted and solid line, respectively. (C) Calibration plot of nomogram in external validation cohort (n = 440). Solid line indicates logistic calibration curve and dotted line represent data for validation cohort. IPC, insignificant prostate cancer.

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  Fig. 2 (A) ROC curve based on the fitted multivariate logistic regression model. Sensitivity and 1-specificity are represented based on a cut-off point (each dot) for IPC predicted probability. (B) The graph of PPV/NPV by nomogram cutoff. The x-axis indicates various cut off values and y-axis indicates the values of PPV/NPV. ROC, receiver operating characteristic; IPC, insignificant prostate cancer; PPV, positive predictive value; NPV, negative predictive value.

Reference

1. Klein EA. What is 'insignificant' prostate carcinoma? Cancer. 2004. 101:1923–1925.

2. Klotz L. Active surveillance for prostate cancer: for whom? J Clin Oncol. 2005. 23:8165–8169.

3. Kattan MW, Eastham JA, Wheeler TM, Maru N, Scardino PT, Erbersdobler A, et al. Counseling men with prostate cancer: a nomogram for predicting the presence of small, moderately differentiated, confined tumors. J Urol. 2003. 170:1792–1797.

4. Nakanishi H, Wang X, Ochiai A, Trpkov K, Yilmaz A, Donnelly JB, et al. A nomogram for predicting low-volume/low-grade prostate cancer: a tool in selecting patients for active surveillance. Cancer. 2007. 110:2441–2447.

5. Chun FK, Haese A, Ahyai SA, Walz J, Suardi N, Capitanio U, et al. Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men. Cancer. 2008. 113:701–709.

6. Shukla-Dave A, Hricak H, Scardino PT. Imaging low-risk prostate cancer. Curr Opin Urol. 2008. 18:78–86.

7. Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA. 1994. 271:368–374.

8. Epstein JI, Chan DW, Sokoll LJ, Walsh PC, Cox JL, Rittenhouse H, et al. Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings. J Urol. 1998. 160:2407–2411.

9. Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo. 1994. 8:439–443.

10. Franks LM. Latent carcinoma of the prostate. J Pathol Bacteriol. 1954. 68:603–616.

11. Jemal A, Thomas A, Murray T, Thun M. Cancer Statistics, 2002. CA Cancer J Clin. 2002. 52:23–47.

12. Steinberg GD, Bales GT, Brendler CB. An analysis of watchful waiting for clinically localized prostate cancer. J Urol. 1998. 159:1431–1436.

13. Walsh PC. Surgery and the reduction of mortality from prostate cancer. N Engl J Med. 2002. 347:839–840.

14. Draisma G, Boer R, Otto SJ, van der Cruijsen IW, Damhuis RA, Schröder FH, et al. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J Natl Cancer Inst. 2003. 95:868–878.

15. Steyerberg EW, Roobol MJ, Kattan MW, van der Kwast TH, de Koning HJ, Schröder FH. Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram. J Urol. 2007. 177:107–112.

16. Wu AH, Whittemore AS, Kolonel LN, John EM, Gallagher RP, West DW, et al. Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada. Cancer Epidemiol Biomarkers Prev. 1995. 4:735–741.

17. Lee SE, Kwak C, Park MS, Lee CH, Kang W, Oh SJ. Ethnic differences in the age-related distribution of serum prostate-specific antigen values: a study in a healthy Korean male population. Urology. 2000. 56:1007–1010.

18. Robbins AS, Koppie TM, Gomez SL, Parikh-Patel A, Mills PK. Differences in prognostic factors and survival among white and Asian men with prostate cancer, California, 1995-2004. Cancer. 2007. 110:1255–1263.

19. Stamey TA, Freiha FS, McNeal JE, Redwine EA, Whittemore AS, Schmid HP. Localized prostate cancer. Relationship of tumor volume to clinical significant for treatment of prostate cancer. Cancer. 1993. 71:933–938.

20. Stamey TA, Donaldson AN, Yemoto CE, McNeal JE, Sözen S, Gill H. Histological and clinical findings in 896 consecutive prostates treated only with radical retropubic prostatectomy: epidemiologic significance of annual changes. J Urol. 1998. 160:2412–2417.

21. Soh S, Kattan MW, Berkman S, Wheeler TM, Scardino PT. Has there been a recent shift in the pathological features and prognosis of patients treated with radical prostatectomy? J Urol. 1997. 157:2212–2218.

22. Noguchi M, Stamey TA, McNeal JE, Yemoto CM. Relationship between systematic biopsies and histological features of 222 radical prostatectomy specimens: lack of prediction of tumor significance for men with nonpalpable prostate cancer. J Urol. 2001. 166:104–109.

23. Lee HW, Seo SI, Jeon SS, Lee HM, Choi HY. Can we predict real T3 stage prostate cancer in patients with clinical T3 (cT3) disease before radical prostatectomy? Yonsei Med J. 2010. 51:700–707.

24. Humphrey PA, Vollmer RT. Percentage carcinoma as a measure of prostatic tumor size in radical prostatectomy tissues. Mod Pathol. 1997. 10:326–333.