|
|
|
| Diagnostic accuracy of cystoscopic biopsy for tumour grade in outpatients with urothelial carcinoma of the bladder and the risk factors of upgrading |
Junjie Fana,b,Hua Liangc,Jinhai Fana,Lei Lia,Guanjun Zhangc,Xinqi Peia,Tao Yanga,Dalin Hea,Kaijie Wua,*( )
|
a Department of Urology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
b Department of Urology, Baoji Center Hospital, Baoji, China
c Department of Pathology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China |
|
|
|
|
Abstract Objective: To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour (TURBT) and explore the risk factors of upgrading. Methods: The medical records of 205 outpatients who underwent diagnostic cystoscopic biopsy before initial TURBT were retrospectively reviewed. Comparative analysis of the tumour grade of biopsy and operation specimens was performed. Tumour grade changing from low-grade to high-grade with or without variant histology was defined as upgrading. Logistic regression analyses were performed to identify the risk factors of upgrading. Results: For the 205 patients, the concordance of tumour grade between specimens obtained from biopsy and operation was 0.639. The concordance for patients who were preoperatively diagnosed with low-grade and high-grade was 0.504 and 0.912, respectively. Univariate and multivariate logistic regression analyses showed that older age, tumour multifocality, high neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte-to-monocyte ratio (LMR) were significantly associated with upgrading (odds ratio ranging from 0.412 to 4.364). The area under the curve of the different multivariate models was improved from 0.752 to 0.821, and decision curve analysis demonstrated a high net benefit when NLR, LMR, and PLR were added. Conclusion: Diagnostic cystoscopic biopsy may not accurately represent the true grade of primary bladder cancer, especially for outpatients with low-grade bladder cancer. Moreover, older age, tumour multifocality, high NLR, PLR, and low LMR are risk factors of upgrading, and systemic inflammatory markers improve the predictive ability.
|
|
Received: 07 July 2020
Available online: 20 January 2023
|
|
Corresponding Authors:
Kaijie Wu
E-mail: kaijie_wu@163.com
|
|
|
| Cystoscopic biopsy (tumour grade) | Postoperative tumour grade, n | Total, n | | Non-tumour | Papillary lesions | PUNLMP | LG | HG | HG with glandular differentiation | HG with squamous differentiation | Sarcoma | Malignant melanoma | | LG | 1 | 0 | 1 | 69 | 61 | 4 | 0 | 1 | 0 | 137 | | HG | 0 | 1 | 0 | 1 | 62 | 2 | 1 | 0 | 1 | 68 | | Total | 1 | 1 | 1 | 70 | 123 | 6 | 1 | 1 | 1 | 205 |
|
|
Concordance of tumour grade between cystoscopic biopsy and TURBT.
|
| Characteristic | Cohort (n=134a) | Group A (n=69) | Group B (n=65) | p-Value | | Age, median (range), year | 63 (25-84) | 59 (25-82) | 65 (28-84) | 0.001 | | Sex, n (%) | 0.547 | | Female | 28 (20.9) | 13 (18.8) | 15 (23.1) | | | Male | 106 (79.1) | 56 (81.2) | 50 (76.9) | | | Smoking status, n (%) | 0.499 | | Never | 70 (52.2) | 38 (55.1) | 32 (49.2) | | | Ever/current | 64 (47.8) | 31 (44.9) | 33 (50.8) | | | Operative methods, n (%) | 0.549 | | Bipolar TURBT | 98 (73.1) | 52 (75.4) | 46 (70.8) | | | KTP laser | 36 (26.9) | 17 (24.6) | 19 (29.2) | | | Tumour number, n (%) | 0.001 | | Single | 76 (56.7) | 50 (72.5) | 26 (40.0) | | | Multiple | 58 (43.2) | 19 (27.5) | 39 (60.0) | | | Tumour diameter, median (range), cm | 2.00 (0.50-4.00) | 1.50 (0.50-3.80) | 2.00 (0.50-4.00) | 0.286 | | NLR, n (%) | 0.004 | | <3.73 | 115 (85.8) | 65 (94.2) | 50 (76.9) | | | ≥3.73 | 19 (14.2) | 4 (5.8) | 15 (23.1) | | | PLR, n (%) | 0.001 | | <123.94 | 79 (59.0) | 50 (72.5) | 29 (44.6) | | | ≥123.94 | 55 (41.0) | 19 (27.5) | 36 (55.4) | | | LMR, n (%) | 0.001 | | <4.96 | 50 (37.3) | 16 (23.2) | 34 (52.3) | | | ≥4.96 | 84 (62.7) | 53 (76.9) | 31 (47.7) | |
|
|
Characteristics of patients who were preoperatively diagnosed with LG and the comparison between Group A (tumour grade unchanged) and Group B (tumour upgrading).
|
| Characteristic | Univariable | Multivariable | | OR | 95% CI | p-Value | OR | 95% CI | p-Value | | Age (continuous) | 1.056 | 1.020-1.093 | 0.002 | 1.049 | 1.005-1.095 | 0.027 | | Sex (female vs. male) | 0.774 | 0.336-1.783 | 0.547 | 0.967 | 0.291-3.213 | 0.957 | | Smoking status (never vs. ever/current) | 1.264 | 0.641-2.493 | 0.499 | 1.595 | 0.640-3.977 | 0.316 | | Operative methods (bipolar TURBT vs. KTP laser) | 1.263 | 0.588-2.716 | 0.549 | 2.385 | 0.868-6.551 | 0.092 | | Tumour number (single vs. multiple) | 3.947 | 1.912-8.148 | 0.001 | 3.757 | 1.583-8.919 | 0.003 | | Tumour diameter (continuous) | 1.290 | 0.768-2.169 | 0.336 | 1.677 | 0.860-3.271 | 0.129 | | NLR (<3.73 vs. ≥3.73) | 4.875 | 1.524-15.596 | 0.008 | 4.364 | 1.068-17.833 | 0.040 | | PLR (<123.94 vs. ≥123.94) | 3.267 | 1.590-6.710 | 0.001 | 3.578 | 1.474-8.685 | 0.005 | | LMR (<4.96 vs. ≥4.96) | 0.275 | 0.131-0.578 | 0.001 | 0.412 | 0.172-0.990 | 0.047 |
|
|
Univariable and multivariate analyses for the association between Group A (tumour grade unchanged) and Group B (tumour upgrading).
|
| Model | AUC | Improvement | p-Value | | Base modela | 0.752 | | | | Base model + NLR | 0.777 | 0.025 | 0.227 | | Base model + PLR | 0.790 | 0.038 | 0.173 | | Base model + LMR | 0.788 | 0.036 | 0.122 | | Base model + NLR + PLR + LMR | 0.821 | 0.069 | 0.036 |
|
|
Improvement in the predictive accuracy of models when adding systemic inflammatory markers to the base model.
|
|
|
Decision curve analysis of the predictive model. Lateral axis line: assumes no patients have upgrading. Grey line: assumes all patients have upgrading. Red line: the base model with age, sex, smoking status, operative methods, tumour diameter, and tumour number. Blue line: the base model adding NLR, PLR, and LMR. The graph gives the expected net benefit per patient relative to the base model with age, sex, smoking status, operative methods, tumour diameter, and tumour number (“treat none”). The unit is the benefit associated with one upgraded patient evaluated with the base model adding NLR, PLR, and LMR. LMR, lymphocyte-to-monocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio.
|
|
|
A nomogram to predict the tumour upgrading of LG diagnosed by cystoscopic biopsy before first-time TURBT. Directions: age, tumour number, NLR, PLR, and LMR positive for an individual patient. A line is drawn upwards to the number of points in each category. The points are totalled, and then a line is drawn downwards to find the probability of upgrading before the first TURBT in patients who were diagnosed with LG by preoperative cystoscopic biopsy. When the total points are over 0.9 or below 0.1 of the probability, this indicates extremely high (over 0.9) or low risk (below 0.1), respectively. LG, low-grade; LMR, lymphocyte-to-monocyte ratio; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; TURBT, transurethral resection of bladder tumour.
|
|
|
Calibration curves of nomogram performance. The bias-corrected calibration plots showed only a limited departure from the ideal predictions. The mean absolute error was 0.03.
|
| [1] |
Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A, Bray F. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 2017; 71:96e108.
doi: S0302-2838(16)30280-9
pmid: 27370177
|
| [2] |
Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet 2009; 374:239e49.
doi: 10.1016/S0140-6736(09)60491-8
pmid: 19520422
|
| [3] |
Rubben H, Lutzeyer W, Fischer N, Deutz F, Lagrange W, Giani G. Natural history and treatment of low and high risk super?cial bladder tumors. J Urol 1988; 139:283e5.
doi: 10.1016/S0022-5347(17)42387-1
|
| [4] |
Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016; 196:1021e9.
doi: 10.1016/j.juro.2016.06.049
pmid: 27317986
|
| [5] |
Miyamoto H, Miller JS, Fajardo DA, Lee TK, Netto GJ, Epstein JI. Non-invasive papillary urothelial neoplasms: the 2004 WHO/ISUP classi?cation system. Pathol Int 2010; 60:1e8.
doi: 10.1111/j.1440-1827.2009.02477.x
pmid: 20055945
|
| [6] |
Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 2005; 66(6 Suppl 1):4e34.
|
| [7] |
Iida S, Kondo T, Kobayashi H, Hashimoto Y, Goya N, Tanabe K. Clinical outcome of high-grade non-muscle-invasive bladder cancer: a long-term single center experience. Int J Urol 2009; 16:287e92.
doi: 10.1111/j.1442-2042.2008.02239.x
pmid: 19207115
|
| [8] |
Nishiyama N, Kitamura H, Maeda T, Takahashi S, Masumori N, Hasegawa T, et al. Clinicopathological analysis of patients with non-muscle-invasive bladder cancer: prognostic value and clinical reliability of the 2004 WHO classi?cation system. Jpn J Clin Oncol 2013; 43:1124e31.
doi: 10.1093/jjco/hyt120
pmid: 23980236
|
| [9] |
Babjuk M, Burger M, Comperat EM, Gontero P, Mosta?d AH, Palou J, et al. European association of urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ)d2019 update. Eur Urol 2019 ; 76:639e57.
doi: S0302-2838(19)30660-8
pmid: 31443960
|
| [10] |
Herr HW, Donat SM. Quality control in transurethral resection of bladder tumours. BJU Int 2008; 102(9 Pt B):1242e6.
|
| [11] |
Li K, Lin T; Chinese Bladder Cancer Consortium; Xue W, Mu X, Xu E, et al. Current status of diagnosis and treatment of bladder cancer in Chinadanalyses of Chinese Bladder Cancer Consortium database. Asian J Urol 2015; 2:63e9.
|
| [12] |
Cheng L, Neumann RM, Nehra A, Spotts BE, Weaver AL, Bostwick DG. Cancer heterogeneity and its biologic implica-tions in the grading of urothelial carcinoma. Cancer 2000; 88: 1663e70.
pmid: 10738225
|
| [13] |
Billis A, Carvalho RB, Mattos AC, Negretti F, Nogueira CR, Oliveira MC, et al. Tumor grade heterogeneity in urothelial bladder carcinomadproposal of a system using combined numbers. Scand J Urol Nephrol 2001; 35:275e9.
pmid: 11676351
|
| [14] |
Bircan S, Candir O, Serel TA. Comparison of WHO Comparison of WHO 1973, WHO/ISUP 1998, WHO 1999 grade and combined scoring systems in evaluation of bladder carcinoma. Urol Int 2004; 73:201e8.
doi: 10.1159/000080828
|
| [15] |
Warrick JI, Sjodahl G, Kaag M, Raman JD, Merrill S, Shuman L, et al. Intratumoral heterogeneity of bladder cancer by mo-lecular subtypes and histologic variants. Eur Urol 2019; 75: 18e22.
doi: S0302-2838(18)30653-5
pmid: 30266310
|
| [16] |
Amin MB, Smith SC, Reuter VE, Epstein JI, Grignon DJ, Hansel DE, et al. Update for the practicing pathologist: the International Consultation on Urologic Disease-European as-sociation of urology consultation on bladder cancer. Mod Pathol 2015; 28:612e30.
doi: 10.1038/modpathol.2014.158
|
| [17] |
Shariat SF, Sfakianos JP, Droller MJ, Karakiewicz PI, Meryn S, Bochner BH. The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int 2010; 105:300e8.
doi: 10.1111/j.1464-410X.2009.09076.x
pmid: 19912200
|
| [18] |
Benson Jr RC, Tomera KM, Kelalis PP. Transitional cell carci-noma of the bladder in children and adolescents. J Urol 1983; 130:54e5.
doi: 10.1016/s0022-5347(17)50950-7
pmid: 6864914
|
| [19] |
Linn JF, Sesterhenn I, Mosto? FK, Schoenberg M. The molec-ular characteristics of bladder cancer in young patients. J Urol 1998; 159:1493e6.
doi: 10.1097/00005392-199805000-00022
pmid: 9554340
|
| [20] |
Janisch F, Yu H, Vetterlein MW, Dahlem R, Engel O, Fisch M, et al. Do younger patients with muscle-invasive bladder can-cer have better outcomes? J Clin Med 2019; 8:1459. https: //doi.org/10.3390/jcm8091459.
doi: 10.3390/jcm8091459
|
| [21] |
Shapur N, Pode D, Katz R, Shapiro A, Yutkin V, Pizov G, et al. Predicting the risk of high-grade bladder cancer using nonin-vasive data. Urol Int 2011; 87:319e24.
doi: 10.1159/000328635
|
| [22] |
Lotan Y, Boorjian SA, Zhang J, Bivalacqua TJ, Porten SP, Wheeler T, et al. Molecular subtyping of clinically localized urothelial carcinoma reveals lower rates of pathological upstaging at radical cystectomy among luminal tumors. Eur Urol 2019; 76:200e6.
doi: S0302-2838(19)30352-5
pmid: 31092337
|
| [23] |
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646e74.
doi: 10.1016/j.cell.2011.02.013
pmid: 21376230
|
| [24] |
Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001; 357:539e45.
doi: 10.1016/S0140-6736(00)04046-0
pmid: 11229684
|
| [25] |
Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Canc 2004:71e8.
|
| [26] |
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140:883e99.
doi: 10.1016/j.cell.2010.01.025
pmid: 20303878
|
| [27] |
Tang X, Wang S, An C, Du P, Yang Y. Preoperative high neutrophil-to-lymphocyte ratio is associated with high-grade bladder cancer. Anticancer Res 2017; 37:4659e63.
pmid: 28739768
|
| [28] |
Rajwa P, Zyczkowski M, Paradysz A, Bujak K, Bryniarski P. Evaluation of the prognostic value of LMR, PLR, NLR, and dNLR in urothelial bladder cancer patients treated with radical cys-tectomy. Eur Rev Med Pharmacol Sci 2018; 22:3027e37.
|
| [29] |
Azab B, Camacho-Rivera M, Taioli E. Average values and racial differences of neutrophil lymphocyte ratio among a nationally representative sample of United States subjects. PloS One 2014; 9:e112361. https://doi.org/10.1371/journal.pone.0112361.
doi: 10.1371/journal.pone.0112361
|
| [1] |
Victor Chalfant,Michael L. BluteJr.,Peter Silberstein. Treatment trends of muscle invasive bladder cancer: Evidence from the Surveillance, Epidemiology, and End Results database, 1988 to 2013[J]. Asian Journal of Urology, 2023, 10(1): 9-18. |
| [2] |
Chinna Babu Dracham,Narendra Kumar,Santosh Kumar,Arun Elangovan,Budhi Singh Yadav,Ravimohan S. Mavuduru,Anupam Lal,Pramod K. Gupta,Rakesh Kapoor. A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer[J]. Asian Journal of Urology, 2022, 9(3): 318-328. |
| [3] |
Yuvaraja B. Thyavihally,Preetham Dev,Santosh Waigankar,Abhinav Pednekar,Nevitha Athikari,Abhijit Raut,Archan Khandekar,Naresh Badlani,Ashishkumar Asari. Intravesical bacillus Calmette-Guerin (BCG) in treating non-muscle invasive bladder cancer—analysis of adverse effects and effectiveness of two strains of BCG (Danish 1331 and Moscow-I)[J]. Asian Journal of Urology, 2022, 9(2): 157-164. |
| [4] |
Lexiaochuan Wen,Cameron J. Britton,Rohan Garje,Benjamin W. Darbro,Vignesh T. Packiam. The emerging role of somatic tumor sequencing in the treatment of urothelial cancer[J]. Asian Journal of Urology, 2021, 8(4): 391-399. |
| [5] |
Marcio Covas Moschovas,Kulthe Ramesh Seetharam Bhat,Cathy Jenson,Vipul R. Patel,Gabriel Ogaya-Pinies. Robtic-assisted radical cystectomy: Literature review[J]. Asian Journal of Urology, 2021, 8(1): 14-19. |
| [6] |
Hugo Otaola-Arca,Rafael Coelho,Vipul R. Patel,Marcelo Orvieto. Totally intracorporeal robot-assisted urinary diversion for bladder cancer (Part 1). Review and detailed characterization of ileal conduit and modified Indiana pouch[J]. Asian Journal of Urology, 2021, 8(1): 50-62. |
| [7] |
Hugo Otaola-Arca,Kulthe Ramesh Seetharam Bhat,Vipul R. Patel,Marcio Covas Moschovas,Marcelo Orvieto. Totally intracorporeal robot-assisted urinary diversion for bladder cancer (part 2). Review and detailed characterization of the existing intracorporeal orthotopic ileal neobladder[J]. Asian Journal of Urology, 2021, 8(1): 63-80. |
| [8] |
Abhishek Tripathi,Shilpa Gupta. Androgen receptor in bladder cancer: A promising therapeutic target[J]. Asian Journal of Urology, 2020, 7(3): 284-290. |
| [9] |
Weibin Xie,Junming Bi,Qiang Wei,Ping Han,Dongkui Song,Lei Shi,Dingwei Ye,Yijun Shen,Xin Gou,Weiyang He,Shaogang Wang,Zheng Liu,Jinhai Fan,Kaijie Wu,Zhiwen Chen,Xiaozhou Zhou,Chuize Kong,Yang Liu,Chunxiao Liu,Abai Xu,Baiye Jin,Guanghou Fu,Wei Xue,Haige Chen,Tiejun Pan,Zhong Tu,Tianxin Lin,Jian Huang. Survival after radical cystectomy for bladder cancer: Multicenter comparison between minimally invasive and open approaches[J]. Asian Journal of Urology, 2020, 7(3): 291-300. |
| [10] |
Sunny Goel,Rahul J. Sinha,Ved Bhaskar,Ruchir Aeron,Ashish Sharma,Vishwajeet Singh. Role of gemcitabine and cisplatin as neoadjuvant chemotherapy in muscle invasive bladder cancer: Experience over the last decade[J]. Asian Journal of Urology, 2019, 6(3): 222-229. |
| [11] |
Ka Wing Wong, Terence Chun-ting Lai, Ada Tsui-lin Ng, Brian Sze-ho Ho, James Hok-leung Tsu, Chiu Fung Tsang, W. K. Ma, Ming Kwong Yiu. Anterior perineal hernia after anterior exenteration[J]. Asian Journal of Urology, 2017, 4(4): 253-255. |
| [12] |
Yu Guang Tan, Ernest Eu, Weber Lau Kam On, Hong Hong Huang. Pretreatment neutrophil-to-lymphocyte ratio predicts worse survival outcomes and advanced tumor staging in patients undergoing radical cystectomy for bladder cancer[J]. Asian Journal of Urology, 2017, 4(4): 239-246. |
| [13] |
David J. McConkey, Woonyoung Choi, Andrea Ochoa, Colin P. N. Dinney. Intrinsic subtypes and bladder cancer metastasis[J]. Asian Journal of Urology, 2016, 3(4): 260-267. |
| [14] |
Thomas Y. Hsueh, Allen W. Chiu. Narrow band imaging for bladder cancer[J]. Asian Journal of Urology, 2016, 3(3): 126-129. |
| [15] |
Wei Wang, Haitao Liu, Shujie Xia. Thulium laser treatment for bladder cancer[J]. Asian Journal of Urology, 2016, 3(3): 130-133. |
|
|
|
|
