PURPOSE: The De Ritis ratio (aspartate aminotransferase/alanine aminotransferase, DRR) has been linked to oncological outcomes in several cancers. We aimed to assess the association of DRR with recurrence-free survival (RFS) and progression-free survival (PFS) in patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a retrospective analysis of 1117 patients diagnosed with NMIBC originating from an established multicenter database. To define the optimal pretreatment DRR cut-off value, we determined a value of 1.2 as having a maximum Youden index value. The overall population was therefore divided into two De Ritis ratio groups using this cut-off (lower, < 1.2 vs. higher, ≥ 1.2). Univariable and multivariable Cox regression analyses were used to investigate the association of DRR with RFS and PFS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). RESULTS: Overall, 405 (36%) patients had a DRR ≥ 1.2. On univariable Cox regression analysis, DRR was significantly associated with RFS (HR: 1.23, 95% CI 1.02-1.47, p = 0.03), but not with PFS (HR: 0.96, 95% CI 0.65-1.44, p = 0.9). On multivariable Cox regression analysis, which adjusted for the effect of established clinicopathologic features, DRR ≥ 1.2 remained significantly associated with worse RFS (HR:1.21, 95% CI 1.00-1.46, p = 0.04). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.683 vs. C-index = 0.681). On DCA the inclusion of DRR did not improve the net-benefit of the prognostic model. CONCLUSION: Despite the statistically significant association of the DRR with RFS in patients with NMIBC, it does not seem to add any prognostic or clinical benefit beyond that of currently available clinical factors.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Comprehensive Cancer Center Vienna General Hospital Medical University of Vienna Währinger Gürtel 18 20 1090 Vienna Austria

Department of Urology Ehime University Graduate School of Medicine Ehime Japan

Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Hospital of Tours Tours France

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

European Association of Urology Research Foundation Arnhem The Netherlands

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

King Faisal Medical City Abha Saudi Arabia

Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran

The National Center for Diabetes Endocrinology and Genetics The University of Jordan Amman Jordan

Zobrazit více v PubMed

Babjuk M, Oosterlinck W, Sylvester R (2019) European association of urology guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). 2019 Edition. Presented at the EAU annual congress, Barcelona, 2019; European Association Urology Guidelines Office. ISBN 978-94-92671-07-3

Xylinas E, Kent M, Kluth L, Pycha A, Comploj E, Svatek RS, Lotan Y, Trinh QD, Karakiewicz PI, Holmang S, et al. Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder. Br J Cancer. 2013;109(6):1460–1466. doi: 10.1038/bjc.2013.372. PubMed DOI PMC

Gontero P, Sylvester R, Pisano F, Joniau S, Vander Eeckt K, Serretta V, Larre S, Di Stasi S, Van Rhijn B, Witjes AJ, et al. Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients. Eur Urol. 2015;67(1):74–82. doi: 10.1016/j.eururo.2014.06.040. PubMed DOI

Svatek RS, Shariat SF, Novara G, Skinner EC, Fradet Y, Bastian PJ, Kamat AM, Kassouf W, Karakiewicz PI, Fritsche HM, et al. Discrepancy between clinical and pathological stage: external validation of the impact on prognosis in an international radical cystectomy cohort. BJU Int. 2011;107(6):898–904. doi: 10.1111/j.1464-410X.2010.09628.x. PubMed DOI

D’Andrea D, Hassler MR, Abufaraj M, Soria F, Ertl IE, Ilijazi D, Mari A, Foerster B, Egger G, Shariat SF. Progressive tissue biomarker profiling in non-muscle-invasive bladder cancer. Expert Rev Anticancer Ther. 2018;18(7):695–703. doi: 10.1080/14737140.2018.1474104. PubMed DOI

Soria F, D'Andrea D, Pohar K, Shariat SF, Lotan Y. Diagnostic, prognostic and surveillance urinary markers in nonmuscle invasive bladder cancer: any role in clinical practice? Curr Opin Urol. 2018;28(6):577–583. doi: 10.1097/MOU.0000000000000545. PubMed DOI

D'Andrea D, Moschini M, Gust K, Abufaraj M, Ozsoy M, Mathieu R, Soria F, Briganti A, Roupret M, Karakiewicz PI, et al. Prognostic role of neutrophil-to-lymphocyte ratio in primary non-muscle-invasive bladder cancer. Clin Genitourin Cancer. 2017;15(5):e755–e764. doi: 10.1016/j.clgc.2017.03.007. PubMed DOI

Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP. Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology. 2003;61(6):1140–1145. doi: 10.1016/S0090-4295(03)00236-X. PubMed DOI

Wu J, Chen L, Wang Y, Tan W, Huang Z. Prognostic value of aspartate transaminase to alanine transaminase (De Ritis) ratio in solid tumors: a pooled analysis of 9400 patients. Onco Targ Therap. 2019;12:5201–5213. doi: 10.2147/OTT.S204403. PubMed DOI PMC

Bezan A, Mrsic E, Krieger D, Stojakovic T, Pummer K, Zigeuner R, Hutterer GC, Pichler M. The preoperative AST/ALT (De Ritis) ratio represents a poor prognostic factor in a cohort of patients with nonmetastatic renal cell carcinoma. J Urol. 2015;194(1):30–35. doi: 10.1016/j.juro.2015.01.083. PubMed DOI

Nishikawa M, Miyake H, Fujisawa M. De Ritis (aspartate transaminase/alanine transaminase) ratio as a significant predictor of recurrence-free survival in patients with upper urinary tract urothelial carcinoma following nephroureterectomy. Urol Oncol. 2016;34(9):e419–e417. doi: 10.1016/j.urolonc.2016.04.001. PubMed DOI

Wang H, Fang K, Zhang J, Jiang Y, Wang G, Zhang H, Chen T, Shi X, Li Y, Duan F, et al. The significance of De Ritis (aspartate transaminase/alanine transaminase) ratio in predicting pathological outcomes and prognosis in localized prostate cancer patients. Int Urol Nephrol. 2017;49(8):1391–1398. doi: 10.1007/s11255-017-1618-7. PubMed DOI

Gorgel SN, Akin Y, Koc EM, Kose O, Ozcan S, Yilmaz Y. Impact of increased aspartate aminotransferase to alanine aminotransferase (De Ritis) ratio in prognosis of testicular cancer. Invest Clin Urol. 2019;60(3):169–175. doi: 10.4111/icu.2019.60.3.169. PubMed DOI PMC

Shariat SF, Milowsky M, Droller MJ. Bladder cancer in the elderly. Urol Oncol. 2009;27(6):653–667. doi: 10.1016/j.urolonc.2009.07.020. PubMed DOI PMC

Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–1033. doi: 10.1126/science.1160809. PubMed DOI PMC

Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell. 2008;134(5):703–707. doi: 10.1016/j.cell.2008.08.021. PubMed DOI

Sookoian S, Pirola CJ. Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine. World J Gastroenterol. 2015;21(3):711–725. doi: 10.3748/wjg.v21.i3.711. PubMed DOI PMC

Ha YS, Kim SW, Chun SY, Chung JW, Choi SH, Lee JN, Kim BS, Kim HT, Yoo ES, Kwon TG, et al. Association between De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) and oncological outcomes in bladder cancer patients after radical cystectomy. BMC Urol. 2019;19(1):10. doi: 10.1186/s12894-019-0439-7. PubMed DOI PMC

Shariat SF, Lotan Y, Vickers A, Karakiewicz PI, Schmitz-Drager BJ, Goebell PJ, Malats N. Statistical consideration for clinical biomarker research in bladder cancer. Urol Oncol. 2010;28(4):389–400. doi: 10.1016/j.urolonc.2010.02.011. PubMed DOI PMC

Shariat SF, Kattan MW, Vickers AJ, Karakiewicz PI, Scardino PT. Critical review of prostate cancer predictive tools. Future Oncol. 2009;5(10):1555–1584. doi: 10.2217/fon.09.121. PubMed DOI PMC

Kluth LA, Black PC, Bochner BH, Catto J, Lerner SP, Stenzl A, Sylvester R, Vickers AJ, Xylinas E, Shariat SF. Prognostic and prediction tools in bladder cancer: a comprehensive review of the literature. Eur Urol. 2015;68(2):238–253. doi: 10.1016/j.eururo.2015.01.032. PubMed DOI

Shariat SF, Semjonow A, Lilja H, Savage C, Vickers AJ, Bjartell A. Tumor markers in prostate cancer I: blood-based markers. Acta Oncol. 2011;50(Suppl 1):61–75. doi: 10.3109/0284186X.2010.542174. PubMed DOI PMC

Canat L, Ataly HA, Agalarov S, Alkan I, Altunrende F. The effect of AST/ALT (De Ritis) ratio on survival and its relation to tumor histopathological variables in patients with localized renal cell carcinoma. Int Braz J Urol Off J Braz Soc Urol. 2018;44(2):288–295. doi: 10.1590/s1677-5538.ibju.2017.0173. PubMed DOI PMC

Ha H, Chung JW, Ha YS, Choi SH, Lee JN, Kim BS, Kim HT, Kim TH, Yoon GS, Kwon TG, et al. Clinical significance of the De Ritis ratio for detecting prostate cancer in a repeat prostate biopsy. Invest Clin Urol. 2019;60(6):447–453. doi: 10.4111/icu.2019.60.6.447. PubMed DOI PMC

Bruchbacher A, Soria F, Hassler M, Shariat SF, D’Andrea D. Tissue biomarkers in nonmuscle-invasive bladder cancer: any role in clinical practice? Curr Opin Urol. 2018;28(6):584–590. doi: 10.1097/MOU.0000000000000546. PubMed DOI

Vartolomei MD, Porav-Hodade D, Ferro M, Mathieu R, Abufaraj M, Foerster B, Kimura S, Shariat SF. Prognostic role of pretreatment neutrophil-to-lymphocyte ratio (NLR) in patients with non-muscle-invasive bladder cancer (NMIBC): a systematic review and meta-analysis. Urol Oncol. 2018;36(9):389–399. doi: 10.1016/j.urolonc.2018.05.014. PubMed DOI

Mbeutcha A, Shariat SF, Rieken M, Rink M, Xylinas E, Seitz C, Lucca I, Mathieu R, Roupret M, Briganti A, et al. Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer. Urol Oncol. 2016;34(11):e417–e424. doi: 10.1016/j.urolonc.2016.05.013. PubMed DOI

Kimura S, Soria F, D’Andrea D, Foerster B, Abufaraj M, Vartolomei MD, Karakiewicz PI, Mathieu R, Moschini M, Rink M, et al. Prognostic value of serum cholinesterase in non-muscle-invasive bladder cancer. Clin Genitourin Cancer. 2018;16(6):e1123–e1132. doi: 10.1016/j.clgc.2018.07.002. PubMed DOI

Bensalah K, Montorsi F, Shariat SF. Challenges of cancer biomarker profiling. Eur Urol. 2007;52(6):1601–1609. doi: 10.1016/j.eururo.2007.09.036. PubMed DOI

Prognostic value of the systemic immune-inflammation index in non-muscle invasive bladder cancer