Top

Published in:

01-08-2013 | Original Article

Influence of age on false positive rates of urine-based tumor markers

Authors: M. Horstmann, T. Todenhöfer, J. Hennenlotter, S. Aufderklamm, J. Mischinger, U. Kuehs, G. Gakis, A. Stenzl, C. Schwentner

Published in: World Journal of Urology | Issue 4/2013

Abstract

Introduction

Several influencing factors on false positive rates (FPRs) of urine-based tumor markers in the detection of urothelial cancer (UC) have been identified. We evaluated age as a possible influencing factor.

Methods

Urinary cytology (Cyt), UroVysion (FISH), ImmunoCyt (uCyt+) and NMP22 were determined in 1,554 patients suspicious for UC of the bladder before cystoscopy and in case of cancer detection before TURB. Additionally, upper urinary tract imaging was performed. Maker sensitivity, specificity and FPRs were evaluated in the entire cohort and in subgroups divided by age into <50, ≥50–70 and ≥70 years. Contingency tables and the Cochrane Armitage tests were used for statistical comparisons.

Results

UC was found in 377 and no UC in 1,177 (75 %) patients. A total of 336 patients were diagnosed with UC of the bladder and 41 with UC of the upper urinary tract. Overall sensitivity and specificity for Cyt were 82 and 82 %: for FISH, 73 and 79 % and for uCyt+, 79 and 75 %, respectively. For NMP22, regardless of the exclusion criteria they were 72 and 34 % and after exclusion of urinary tract infection (UTI) or prior to manipulation 46 and 86 %, respectively. Significantly higher FPRs were found with increasing age for Cyt (p = 0.001), a trend to higher FPRs for uCyt+ (p = 0.11) and almost no difference for FISH (p = 0.63). For NMP22, differences became significant after exclusion of patients with UTI or prior manipulation (p = 0.02).

Conclusions

The results of the present study give evidence that false positive rates of Cyt and NMP22 increase with age indicating that age should be respected for their correct interpretation.

Tilki D, Burger M, Dalbagni G et al (2011) Urine markers for detection and surveillance of non-muscle-invasive bladder cancer. Eur Urol 60:484–492PubMedCrossRef

Babjuk M, Oosterlinck W, Sylvester R et al (2011) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol 59:997–1008PubMedCrossRef

Lotan Y, Svatek RS, Sagalowsky AI (2006) Should we screen for bladder cancer in a high-risk population? A cost per life-year saved analysis. Cancer 1(107):982–990CrossRef

Svatek RS, Lotan Y, Karakiewizc PI, Shariat SF (2008) Screening for bladder cancer using urine-based tumor markers. Minerva Urol Nefrol 60:247–253PubMed

Hennenlotter J, Huber S, Todenhofer T et al (2011) Point-of-care tests for bladder cancer: the influencing role of hematuria. Adv Urol 2011:937561PubMedCrossRef

Pesch B, Nasterlack M, Eberle F et al (2011) The role of haematuria in bladder cancer screening among men with former occupational exposure to aromatic amines. BJU Int 108:546–552PubMedCrossRef

Todenhofer T, Hennenlotter J, Witstruk M et al (2012) Influence of renal excretory function on the performance of urine based markers to detect bladder cancer. J Urol 187:68–73PubMedCrossRef

Todenhofer T, Hennenlotter J, Tews V et al (2011) Impact of different grades of microscopic hematuria on the performance of urine-based markers for the detection of urothelial carcinoma. Urol Oncol

Shariat SF, Sfakianos JP, Droller MJ, Karakiewicz PI, Meryn S, Bochner BH (2010) The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int 105:300–308PubMedCrossRef

10.

Madeb R, Messing EM (2004) Gender, racial and age differences in bladder cancer incidence and mortality. Urol Oncol 22:86–92PubMedCrossRef

11.

Papanicolaou GN, Marshall VF (1945) Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science 18(101):519–520CrossRef

12.

Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL (2005) The 2005 international society of urological pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma. Am J Pathol 29:1228–1242CrossRef

13.

Riesz P, Lotz G, Paska C et al (2007) Detection of bladder cancer from the urine using fluorescence in situ hybridization technique. Pathol Oncol Res 13:187–194PubMedCrossRef

14.

Kipp BR, Tyner HL, Campion MB et al (2008) Chromosomal alterations detected by fluorescence in situ hybridization in urothelial carcinoma and rarer histologic variants of bladder cancer. Am J Clin Pathol 130:552–559PubMedCrossRef

15.

Mian C, Pycha A, Wiener H, Haitel A, Lodde M, Marberger M (1999) Immunocyt: a new tool for detecting transitional cell cancer of the urinary tract. J Urol 161:1486–1489PubMedCrossRef

16.

Greene KL, Berry A, Konety BR (2006) Diagnostic utility of the immunoCyt/uCyt+ test in bladder cancer. Rev Urol 8:190–197PubMed

17.

Karakiewicz PI, Benayoun S, Zippe C et al (2006) Institutional variability in the accuracy of urinary cytology for predicting recurrence of transitional cell carcinoma of the bladder. BJU Int 97:997–1001PubMedCrossRef

18.

Bubendorf L (2011) Multiprobe fluorescence in situ hybridization (UroVysion) for the detection of urothelial carcinoma—FISHing for the right catch. Acta Cytol 55:113–119PubMedCrossRef

19.

Hajdinjak T (2008) UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urol Oncol 26:646–651PubMedCrossRef

20.

Mian C, Maier K, Comploj E et al (2006) uCyt+/ImmunoCyt in the detection of recurrent urothelial carcinoma: an update on 1991 analyses. Cancer 25(108):60–65CrossRef

21.

Horstmann M, Patschan O, Hennenlotter J, Senger E, Feil G, Stenzl A (2009) Combinations of urine-based tumour markers in bladder cancer surveillance. Scand J Urol Nephrol 43:461–466PubMedCrossRef

22.

Shariat SF, Karam JA, Lotan Y, Karakiewizc PI (2008) Critical evaluation of urinary markers for bladder cancer detection and monitoring. Rev Urol 10:120–135PubMed

23.

Atsu N, Ekici S, Oge OO, Ergen A, Hascelik G, Ozen H (2002) False-positive results of the NMP22 test due to hematuria. J Urol 167:555–558PubMedCrossRef

24.

Sharma S, Zippe CD, Pandrangi L, Nelson D, Agarwal A (1999) Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat. J Urol 162:53–57PubMedCrossRef

25.

Huber S, Schwentner C, Taeger D et al (2012) Nuclear matrix protein-22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study. BJU Int

26.

Taylor JA 3rd, Kuchel GA (2009) Bladder cancer in the elderly: clinical outcomes, basic mechanisms, and future research direction. Nat Clin Pract Urol 6:135–144PubMedCrossRef

27.

Raitanen MP, Aine R, Rintala E et al (2002) Differences between local and review urinary cytology in diagnosis of bladder cancer an interobserver multicenter analysis. Eur Urol 41:284–289PubMedCrossRef

28.

Savic S, Zlobec I, Thalmann GN et al (2009) The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmuscle-invasive bladder cancer after intravesical Bacillus Calmette-Guerin therapy. Int J Cancer 15(124):2899–2904CrossRef

29.

Gofrit ON, Zorn KC, Silvestre J et al (2008) The predictive value of multi-targeted fluorescent in situ hybridization in patients with history of bladder cancer. Urol Oncol 26:246–249PubMedCrossRef

30.

Ponsky LE, Sharma S, Pandrangi L et al (2001) Screening and monitoring for bladder cancer: refining the use of NMP22. J Urol 166:75–78PubMedCrossRef

Title: Influence of age on false positive rates of urine-based tumor markers
Authors: M. Horstmann
T. Todenhöfer
J. Hennenlotter
S. Aufderklamm
J. Mischinger
U. Kuehs
G. Gakis
A. Stenzl
C. Schwentner
Publication date: 01-08-2013
Publisher: Springer Berlin Heidelberg
Published in: World Journal of Urology / Issue 4/2013
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-012-0906-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Influence of age on false positive rates of urine-based tumor markers

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2013

Pre-operative assessment of living renal transplant donors with state-of-the-art imaging modalities: computed tomography angiography versus magnetic resonance angiography in 118 patients

Periarterial papaverine improves early postoperative renal function after retroperitoneoscopic partial nephrectomy

Male chronic pelvic pain syndrome and the role of interdisciplinary pain management

A 2-year follow-up of quality of life, pain, and psychosocial factors in patients with chronic prostatitis/chronic pelvic pain syndrome and their spouses

Role of pelvic phased array magnetic resonance imaging in staging of prostate cancer specifically in patients diagnosed with clinically locally advanced tumours by digital rectal examination

Classification and treatment of men with chronic prostatitis/chronic pelvic pain syndrome using the UPOINT system