Abstract
Inflammation-based markers, including the C-reactive protein/albumin ratio (CAR), lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), Onodera’s prognostic nutritional index (PNI), and Glasgow Prognostic Score (GPS), have been demonstrated to serve as prognostic indicators in various malignancies. This study aimed to evaluate their potential predictive value for colorectal cancer (CRC) in the elderly. We retrospectively evaluated 163 patients with CRC, aged 80 years and older, who had undergone curative surgery. The receiver operating characteristic curve analyses and the corresponding areas under the curve (AUCs) were used to determine and compare the discriminatory ability of the inflammation-based markers. Besides, the associations of inflammatory markers and clinical characteristics with overall survival (OS), relapse-free survival (RFS), and cancer-specific survival (CSS) were analyzed. The CAR had a significantly larger AUC than the GPS, PLR, NLR, and LMR (p = 0.006, 0.012, 0.018, and 0.002, respectively), except for the PNI (p = 0.052). The optimal cut-off value was 0.106 for the CAR and 44.894 for the PNI. Moreover, a CAR ≥ 0.106 turned out to be significantly associated with worse 5-year OS, RFS, and CSS compared with a CAR < 0.106. The multivariate analysis indicated that the CAR ≥ 0.106 was an independent prognostic factor for poor OS (HR = 3.596, p = 0.0006), RFS (HR = 2.945, p = 0.003), and CSS (HR = 4.411, p = 0.02). CAR is a useful and promising prognostic marker in elderly patients undergoing curative surgery for CRC.
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The datasets analysed during the current study are available from the corresponding author on reasonable request.
References
Siegel RL, Miller KD, Fedewa SA et al (2017) Colorectal cancer statistics, 2017. CA Cancer J Clin 67:177–193. https://doi.org/10.3322/caac.21395
Extermann M, Aapro M, Bernabei R et al (2005) Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol 55:241–252. https://doi.org/10.1016/j.critrevonc.2005.06.003
Diakos CI, Charles KA, McMillan DC, Clarke SJ (2014) Cancer-related inflammation and treatment effectiveness. Lancet Oncol 15:e493–e503. https://doi.org/10.1016/S1470-2045(14)70263-3
Dupré A, Malik HZ (2018) Inflammation and cancer: what a surgical oncologist should know. Eur J Surg Oncol 44:566–570. https://doi.org/10.1016/j.ejso.2018.02.209
Furman D, Campisi J, Verdin E et al (2019) Chronic inflammation in the etiology of disease across the life span. Nat Med 25:1822–1832. https://doi.org/10.1038/s41591-019-0675-0
Hashiguchi Y, Muro K, Saito Y et al (2020) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines. Int J Clin Oncol 25:1–42. https://doi.org/10.1007/s10147-019-01485-z
Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213. https://doi.org/10.1097/01.sla.0000133083.54934.ae
DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845. https://doi.org/10.2307/2531595
Song Y, Yang Y, Gao P et al (2017) The preoperative neutrophil to lymphocyte ratio is a superior indicator of prognosis compared with other inflammatory biomarkers in resectable colorectal cancer. BMC Cancer 17:744. https://doi.org/10.1186/s12885-017-3752-0
Kim HJ, Lee SY, Kim DS et al (2020) Inflammatory markers as prognostic indicators in pancreatic cancer patients who underwent gemcitabine-based palliative chemotherapy. Korean J Intern Med 35:171–184. https://doi.org/10.3904/kjim.2018.076
Fairclough E, Cairns E, Hamilton J, Kelly C (2009) Evaluation of a modified early warning system for acute medical admissions and comparison with C-reactive protein/albumin ratio as a predictor of patient outcome. Clin Med (Lond) 9:30–33. https://doi.org/10.7861/clinmedicine.9-1-30
Ranzani OT, Zampieri FG, Forte DN, Azevedo LC, Park M (2013) C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS ONE 8:e59321. https://doi.org/10.1371/journal.pone.0059321
Kinoshita A, Onoda H, Imai N et al (2015) The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma. Ann Surg Oncol 22:803–810. https://doi.org/10.1245/s10434-014-4048-0
Saito H, Kono Y, Murakami Y et al (2018) Prognostic significance of the preoperative ratio of C-reactive protein to albumin and neutrophil–lymphocyte ratio in gastric cancer patients. World J Surg 42:1819–1825. https://doi.org/10.1007/s00268-017-4400-1
Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Shibuya N, Kubota K (2016) Clinical significance of the C-reactive protein to albumin ratio for survival after surgery for colorectal cancer. Ann Surg Oncol 23:900–907. https://doi.org/10.1245/s10434-015-4948-7
Huang A, Tsavellas G (2001) Acute-phase protein, survival and tumour recurrence in patients with colorectal cancer. Br J Surg 88:1127–1128
Falconer JS, Fearon KC, Ross JA, Elton R, Wigmore SJ, Garden OJ, Carter DC (1995) Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer 75:2077–2082. https://doi.org/10.1002/1097-0142(19950415)75:8%3C2077::AID-CNCR2820750808%3E3.0.CO;2-9
Karakiewicz PI, Hutterer GC, Trinh QD et al (2007) C-reactive protein is an informative predictor of renal cell carcinoma-specific mortality: a European study of 313 patients. Cancer 110:1241–1247. https://doi.org/10.1002/cncr.22896
Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444. https://doi.org/10.1038/nature07205
Gupta D, Lis CG (2010) Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiological literature. Nutr J 9:69. https://doi.org/10.1186/1475-2891-9-69
Lai CC, You JF, Yeh CY, Chen JS, Tang R, Wang JY, Chin CC (2011) Low preoperative serum albumin in colon cancer: a risk factor for poor outcome. Int J Colorectal Dis 26:473–481. https://doi.org/10.1007/s00384-010-1113-4
Oñate-Ocaña LF, Aiello-Crocifoglio V, Gallardo-Rincón D et al (2007) Serum albumin as a significant prognostic factor for patients with gastric carcinoma. Ann Surg Oncol 14:381–389. https://doi.org/10.1245/s10434-006-9093-x
Tominaga T, Nonaka T, Hisanaga M et al (2020) Prognostic value of the preoperative prognostic nutritional index in oldest-old patients with colorectal cancer. Surg Today 50:449–459. https://doi.org/10.1007/s00595-019-01910-w
Watanabe M, Iwatsuki M, Iwagami S et al (2012) Prognostic nutritional index predicts outcomes of gastrectomy in the elderly. World J Surg 36:1632–1639. https://doi.org/10.1007/s00268-012-1526-z
Sakurai K, Tamura T, Toyokawa T et al (2016) Low preoperative prognostic nutritional index predicts poor survival post-gastrectomy in elderly patients with gastric cancer. Ann Surg Oncol 23:3669–3676. https://doi.org/10.1245/s10434-016-5272-6
McMillan DC (2013) The systemic inflammation-based Glasgow prognostic score: a decade of experience in patients with cancer. Cancer Treat Rev 39:534–540. https://doi.org/10.1016/j.ctrv.2012.08.003
Hirahara N, Matsubara T, Mizota Y et al (2016) Prognostic value of preoperative inflammatory response biomarkers in patients with esophageal cancer who undergo a curative thoracoscopic esophagectomy. BMC Surg 16:66. https://doi.org/10.1186/s12893-016-0179-5
Valiathan R, Ashman M, Asthana D (2016) Effects of ageing on the immune system: infants to elderly. Scand J Immunol 83:255–266. https://doi.org/10.1111/sji.12413
Balduini CL, Noris P (2014) Platelet count and aging. Haematologica 99:953–955. https://doi.org/10.3324/haematol.2014.106260
Shibutani M, Maeda K, Nagahara H et al (2016) Prognostic significance of the preoperative ratio of C-reactive protein to albumin in patients with colorectal cancer. Anticancer Res 36:995–1001
Fried LP, Tangen CM, Walston J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146–M156. https://doi.org/10.1093/gerona/56.3.M146
Velissaris D, Pantzaris N, Koniari I et al (2017) C-reactive protein and frailty in the elderly: a literature review. J Clin Med Res 9:461–465. https://doi.org/10.14740/jocmr2959w
Serra-Rexach JA, Jimenez AB, García-Alhambra MA et al (2012) Differences in the therapeutic approach to colorectal cancer in young and elderly patients. Oncologist 17:1277–1285. https://doi.org/10.1634/theoncologist.2012-0060
Oh BY, Huh JW, Kim HC et al (2018) Oncologic outcome of colorectal cancer patients over age 80: a propensity score-matched analysis. Int J Colorectal Dis 33:1011–1018. https://doi.org/10.1007/s00384-018-3028-4
Chang GJ, Skibber JM, Feig BW, Rodriguez-Bigas M (2007) Are we undertreating rectal cancer in the elderly? An epidemiologic study. Ann Surg 246:215–221. https://doi.org/10.1097/SLA.0b013e318070838f
Hirahara N, Tajima Y, Fujii Y et al (2018) Preoperative prognostic nutritional index predicts long-term outcome in gastric cancer: a propensity score-matched analysis. Anticancer Res 38:4735–4746. https://doi.org/10.21873/anticanres.12781
Sakurai K, Kubo N, Tamamori Y et al (2019) Long-term survival estimates in older patients with pathological stage I gastric cancer undergoing gastrectomy: duocentric analysis of simplified scoring system. J Geriatr Oncol 10:604–609. https://doi.org/10.1016/j.jgo.2019.01.003
Hashimoto T, Kurokawa Y, Mikami J et al (2019) Postoperative long-term outcomes in elderly patients with gastric cancer and risk factors for death from other diseases. World J Surg 43:2885–2893. https://doi.org/10.1007/s00268-019-05109-5
Takahashi T, Kaneoka Y, Maeda A et al (2020) The preoperative prognostic nutrition index is a prognostic indicator for survival in elderly gastric cancer patients after gastrectomy: a propensity score-matched analysis. Updates Surg 72:483–491. https://doi.org/10.1007/s13304-020-00745-2
Xishan Z, Ye Z, Feiyan M et al (2020) The role of prognostic nutritional index for clinical outcomes of gastric cancer after total gastrectomy. Sci Rep 10:17373. https://doi.org/10.1038/s41598-020-74525-8
Hirahara N, Matsubara T, Hayashi H et al (2015) Impact of inflammation-based prognostic score on survival after curative thoracoscopic esophagectomy for esophageal cancer. Eur J Surg Oncol 41:1308–1315. https://doi.org/10.1016/j.ejso.2015.07.008
Kadokura M, Ishida Y, Tatsumi A et al (2016) Performance status and neutrophil-lymphocyte ratio are important prognostic factors in elderly patients with unresectable pancreatic cancer. J Gastrointest Oncol 7:982–988. https://doi.org/10.21037/jgo.2016.06.06
Zhou YC, Chen LL, Xu HB et al (2018) Aging-related prognosis analysis of definitive radiotherapy for very elderly esophageal cancer. Cancer Med 7:1837–1844. https://doi.org/10.1002/cam4.1456
Chang JW, Jung DH, Park JC et al (2020) Long-term outcomes and prognostic factors of endoscopic submucosal dissection for early gastric cancer in patients aged nts years. Cancers (Basel) 12:3222. https://doi.org/10.3390/cancers12113222
Li Q, Huang LY, Xue HP (2020) Comparison of prognostic factors in different age groups and prognostic significance of neutrophil-lymphocyte ratio in patients with gastric cancer. World J Gastrointest Oncol 12:1146–1166. https://doi.org/10.4251/wjgo.v12.i10.1146
Hashimoto S, Tominaga T, Nonaka T et al (2020) The C-reactive protein to albumin ratio predicts postoperative complications in oldest-old patients with colorectal cancer. Int J Colorectal Dis 35:423–431. https://doi.org/10.1007/s00384-019-03491-z
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Material preparation, data collection were performed by KT, SM, YK, and SH. Analysis were performed by KT and SO. The first draft of the manuscript was written by KT and SO and all authors commented on previous version of the manuscript. All authors read and approved the final manuscript.
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Tamai, K., Okamura, S., Makino, S. et al. C-reactive protein/albumin ratio predicts survival after curative surgery in elderly patients with colorectal cancer. Updates Surg 74, 153–162 (2022). https://doi.org/10.1007/s13304-021-01011-9
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DOI: https://doi.org/10.1007/s13304-021-01011-9