The Pretreatment Controlling Nutritional Status Score in Ovarian Cancer: Influence on Prognosis, Surgical Outcome, and Postoperative Complication Rate

Abstract

Introduction The Controlling Nutritional (CONUT) Status score is an established predictor of impaired prognosis in patients with solid tumors. The aim of this study was to investigate the prognostic value of the CONUT score for overall survival and perioperative complication rates in patients with epithelial ovarian cancer.

Patients In this retrospective study we assessed the data of 337 consecutive patients with ovarian cancer. The CONUT score was associated with surgical outcome, postoperative complications and clinicopathological parameters. We used univariate log-rank test and multivariable Cox regression models to evaluate the association between pretreatment CONUT scores and survival.

Results A low CONUT score (0 – 2) was associated with an early FIGO stage (p = 0.004), complete tumor resection (p < 0.001), less neoadjuvant chemotherapy (p = 0.017) and other histologies than serous cystadenocarcinoma (p = 0.006). Postoperative complications were observed in 51.4% and 60.5% of patients with a CONUT score of 0 – 2 and a score > 2, respectively (p = 0.161). A shorter overall survival was observed in patients with a CONUT score > 2 compared to patients with a low CONUT score, with 5-year overall survival rates of 31.5% and 58.7%, respectively (p < 0.001). In multivariable analysis, both advanced age (p < 0.001) and FIGO stage (p < 0.001), residual disease (p < 0.001) and a high CONUT score (p = 0.048) were independently associated with unfavorable overall survival.

Conclusion Pretreatment CONUT score is an independent prognostic marker for overall survival and associated with successful surgery. Patients with a high CONUT score might benefit from pretreatment nutritional intervention.

Zusammenfassung

Einleitung Der Controlling Nutritional (CONUT) Status Score ist ein etablierter Prädiktor für eine eingeschränkte Prognose bei Patienten mit soliden Tumoren. Ziel dieser Studie war es, den prognostischen Wert des CONUT-Scores für das Gesamtüberleben und für perioperative Komplikationsraten bei Patientinnen mit epithelialem Ovarialkarzinom zu untersuchen.

Patientinnen In dieser retrospektiven Studie wurden die Daten von 337 konsekutiv aufgenommenen Patientinnen mit Ovarialkarzinom analysiert. Der CONUT-Score war mit dem Operationsergebnis, den postoperativen Komplikationen sowie den klinisch-pathologischen Parametern assoziiert. Wir verwendeten univariate Log-Rank-Tests sowie multivariable Cox-Regressionsmodelle, um die Assoziation zwischen dem CONUT-Score vor Beginn der Behandlung und das Überleben zu evaluieren.

Ergebnisse Ein niedriger CONUT-Score (0 – 2) war mit einem frühen FIGO-Stadium (p = 0,004), einer vollständigen Resektion des Tumors (p < 0,001), weniger neoadjuvanter Chemotherapie (p = 0,017) und Tumoren, die keine seröse Zystadenokarzinome waren (p = 0,006), assoziiert. Postoperative Komplikationen traten bei 51,4% bzw. 60,5% von Patientinnen mit einem CONUT-Score von 0 – 2 bzw. einem Score von > 2 auf (p = 0,161). Patientinnen mit einem CONUT-Score von > 2 hatten ein kürzeres Gesamtüberleben verglichen mit Patientinnen mit einem niedrigen CONUT-Score, mit einer 5-Jahres-Überlebensrate von 31,5% bzw. 58,7% für die jeweilige Gruppe (p < 0,001). Die multivariable Analyse ergab, dass fortgeschrittenes Alter (p < 0,001), FIGO-Stadium (p < 0,001), Resterkrankung (p < 0,001) und hoher CONUT-Score (p = 0,048) unabhängig voneinander mit ungünstigen Überlebensraten assoziiert waren.

Schlussfolgerungen Der CONUT-Score vor Beginn der Behandlung ist ein unabhängiger prognostischer Marker für das Gesamtüberleben und ist mit dem Operationserfolg assoziiert. Patientinnen mit einem hohen CONUT-Score könnten von einer Ernährungsintervention vor Beginn der Behandlung profitieren.

Key words

ovarian cancer - ovarian neoplasms - malabsorption syndromes - postoperative complications

Schlüsselwörter

Ovarialkarzinom - ovarielle Neoplasie - Malabsorptionssyndrome - postoperative Komplikationen

Publication History

Received: 05 May 2021

Accepted after revision: 22 August 2021

Article published online:
10 January 2022

• References

• 1 Torre LA, Bray F, Siegel RL. et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108 DOI: 10.3322/caac.21262.
• 2 Ataseven B, du Bois A, Reinthaller A. et al. Pre-operative serum albumin is associated with post-operative complication rate and overall survival in patients with epithelial ovarian cancer undergoing cytoreductive surgery. Gynecol Oncol 2015; 138: 560-565 DOI: 10.1016/j.ygyno.2015.07.005.
• 3 Lafleur J, Hefler-Frischmuth K, Grimm C. et al. Prognostic Value of Serum Creatinine Levels in Patients with Epithelial Ovarian Cancer. Anticancer Res 2018; 38: 5127-5130 DOI: 10.21873/anticanres.12834.
• 4 Reiser E, Aust S, Seebacher V. et al. Preoperative C-reactive protein serum levels as a predictive diagnostic marker in patients with adnexal masses. Gynecol Oncol 2017; 147: 690-694 DOI: 10.1016/j.ygyno.2017.09.018.
• 5 Seebacher V, Aust S, DʼAndrea D. et al. Development of a tool for prediction of ovarian cancer in patients with adnexal masses: Value of plasma fibrinogen. PloS One 2017; 12: e0182383 DOI: 10.1371/journal.pone.0182383.
• 6 Aust S, Knogler T, Pils D. et al. Skeletal Muscle Depletion and Markers for Cancer Cachexia Are Strong Prognostic Factors in Epithelial Ovarian Cancer. PloS One 2015; 10: e0140403 DOI: 10.1371/journal.pone.0140403.
• 7 Kumar A, Torres ML, Cliby WA. et al. Inflammatory and Nutritional Serum Markers as Predictors of Peri-operative Morbidity and Survival in Ovarian Cancer. Anticancer Res 2017; 37: 3673-3677 DOI: 10.21873/anticanres.11738.
• 8 Yim GW, Eoh KJ, Kim SW. et al. Malnutrition Identified by the Nutritional Risk Index and Poor Prognosis in Advanced Epithelial Ovarian Carcinoma. Nutr Cancer 2016; 68: 772-779 DOI: 10.1080/01635581.2016.1159702.
• 9 Feng Z, Wen H, Ju X. et al. The preoperative prognostic nutritional index is a predictive and prognostic factor of high-grade serous ovarian cancer. BMC Cancer 2018; 18: 883 DOI: 10.1186/s12885-018-4732-8.
• 10 Chen G, Zhu L, Yang Y. et al. Prognostic Role of Neutrophil to Lymphocyte Ratio in Ovarian Cancer: A Meta-Analysis. Technol Cancer Res Treat 2018; 17: 1533033818791500 DOI: 10.1177/1533033818791500.
• 11 Gao XP, Liu YH, Liu ZY. et al. Pretreatment lymphocyte-to-monocyte ratio as a predictor of survival among patients with ovarian cancer: a meta-analysis. Cancer Manag Res 2019; 11: 1907-1920 DOI: 10.2147/CMAR.S184970.
• 12 Tian C, Song W, Tian X. et al. Prognostic significance of platelet-to-lymphocyte ratio in patients with ovarian cancer: A meta-analysis. Eur J Clin Invest 2018; 48: e12917 DOI: 10.1111/eci.12917.
• 13 Omichi C, Nakamura K, Haraga J. et al. Glasgow prognostic score is an independent marker for poor prognosis with all cases of epithelial ovarian cancer. Cancer Med 2016; 5: 1074-1080 DOI: 10.1002/cam4.681.
• 14 Ignacio de Ulibarri J, Gonzalez-Madrono A, de Villar NG. et al. CONUT: a tool for controlling nutritional status. First validation in a hospital population. Nutr Hosp 2005; 20: 38-45
• 15 Li W, Li M, Wang T. et al. Controlling Nutritional Status (CONUT) score is a prognostic factor in patients with resected breast cancer. Sci Rep 2020; 10: 6633 DOI: 10.1038/s41598-020-63610-7.
• 16 Tokunaga R, Sakamoto Y, Nakagawa S. et al. CONUT: a novel independent predictive score for colorectal cancer patients undergoing potentially curative resection. Int J Colorectal Dis 2017; 32: 99-106 DOI: 10.1007/s00384-016-2668-5.
• 17 Yoshida N, Baba Y, Shigaki H. et al. Preoperative Nutritional Assessment by Controlling Nutritional Status (CONUT) is Useful to estimate Postoperative Morbidity After Esophagectomy for Esophageal Cancer. World J Surg 2016; 40: 1910-1917 DOI: 10.1007/s00268-016-3549-3.
• 18 Zhang W, Wu Y, Zhang Z. et al. Controlling Nutritional Status score: A new prognostic indicator for patients with oligometastatic prostate cancer. Curr Probl Cancer 2019; 43: 461-470 DOI: 10.1016/j.currproblcancer.2019.02.001.
• 19 Li Y, Zhang C, Ji R. et al. Prognostic significance of the controlling nutritional status (CONUT) score in epithelial ovarian cancer. Int J Gynecol Cancer 2020; 30: 74-82 DOI: 10.1136/ijgc-2019-000865.
• 20 Colombo N, Sessa C, Bois AD. et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Int J Gynecol Cancer 2019; DOI: 10.1136/ijgc-2019-000308.
• 21 Toyokawa T, Kubo N, Tamura T. et al. The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective study. BMC Cancer 2016; 16: 722 DOI: 10.1186/s12885-016-2696-0.
• 22 Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205-213
• 23 Claussen C, Rody A, Hanker L. Treatment of Recurrent Epithelial Ovarian Cancer. Geburtshilfe Frauenheilkd 2020; 80: 1195-1204 DOI: 10.1055/a-1128-0280.
• 24 Liang Y, Hou T, Que Y. et al. Elevated Controlling Nutritional Status (CONUT) Score is Associated with Poor Long-term Survival in Patients with Low-grade Soft-tissue Sarcomas Treated with Surgical Resection. Clin Orthop Relat Res 2019; 477: 2287-2295 DOI: 10.1097/CORR.0000000000000767.
• 25 Kang M, Chang CT, Sung HH. et al. Prognostic Significance of Pre- to Postoperative Dynamics of the Prognostic Nutritional Index for Patients with Renal Cell Carcinoma Who Underwent Radical Nephrectomy. Ann Surg Oncol 2017; 24: 4067-4075 DOI: 10.1245/s10434-017-6065-2.
• 26 Secker DJ, Jeejeebhoy KN. Subjective Global Nutritional Assessment for children. Am J Clin Nutr 2007; 85: 1083-1089 DOI: 10.1093/ajcn/85.4.1083.
• 27 Kolbl H, Bartl T. Obesity in Gynecologic Oncology. Geburtshilfe Frauenheilkd 2020; 80: 1205-1211 DOI: 10.1055/a-1124-7139.
• 28 Kuroda D, Sawayama H, Kurashige J. et al. Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer 2018; 21: 204-212 DOI: 10.1007/s10120-017-0744-3.
• 29 Ge LN, Wang F. Prognostic significance of preoperative serum albumin in epithelial ovarian cancer patients: a systematic review and dose-response meta-analysis of observational studies. Cancer Manag Res 2018; 10: 815-825 DOI: 10.2147/CMAR.S161876.
• 30 Gadgil MD, Anderson CA, Kandula NR. et al. Dietary patterns are associated with metabolic risk factors in South Asians living in the United States. J Nutr 2015; 145: 1211-1217 DOI: 10.3945/jn.114.207753.
• 31 Oliver MF. Serum cholesterol–the knave of hearts and the joker. Lancet 1981; 2: 1090-1095 DOI: 10.1016/s0140-6736(81)91286-1.
• 32 Ahn J, Lim U, Weinstein SJ. et al. Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer. Cancer Epidemiol Biomarkers Prev 2009; 18: 2814-2821 DOI: 10.1158/1055-9965.EPI-08-1248.
• 33 Gooden MJ, de Bock GH, Leffers N. et al. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer 2011; 105: 93-103 DOI: 10.1038/bjc.2011.189.
• 34 Carli F, Zavorsky GS. Optimizing functional exercise capacity in the elderly surgical population. Curr Opin Clin Nutr Metab Care 2005; 8: 23-32 DOI: 10.1097/00075197-200501000-00005.
• 35 von Haehling S, Anker SD. Prevalence, incidence and clinical impact of cachexia: facts and numbers-update 2014. J Cachexia Sarcopenia Muscle 2014; 5: 261-263 DOI: 10.1007/s13539-014-0164-8.
• 36 Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev 2009; 89: 381-410 DOI: 10.1152/physrev.00016.2008.
• 37 Marin Caro MM, Laviano A, Pichard C. Nutritional intervention and quality of life in adult oncology patients. Clin Nutr 2007; 26: 289-301 DOI: 10.1016/j.clnu.2007.01.005.
• 38 Rodrigues CS, Lacerda MS, Chaves GV. Patient Generated Subjective Global Assessment as a prognosis tool in women with gynecologic cancer. Nutrition 2015; 31: 1372-1378 DOI: 10.1016/j.nut.2015.06.001.
• 39 Celik JB, Gezginc K, Ozcelik K. et al. The role of immunonutrition in gynecologic oncologic surgery. Eur J Gynaecol Oncol 2009; 30: 418-421
• 40 Minig L, Biffi R, Zanagnolo V. et al. Reduction of postoperative complication rate with the use of early oral feeding in gynecologic oncologic patients undergoing a major surgery: a randomized controlled trial. Ann Surg Oncol 2009; 16: 3101-3110 DOI: 10.1245/s10434-009-0681-4.
• 41 Nelson G, Bakkum-Gamez J, Kalogera E. et al. Guidelines for perioperative care in gynecologic/oncology: Enhanced Recovery After Surgery (ERAS) Society recommendations-2019 update. Int J Gynecol Cancer 2019; 29: 651-668 DOI: 10.1136/ijgc-2019-000356.
• 42 Yeung SE, Hilkewich L, Gillis C. et al. Protein intakes are associated with reduced length of stay: a comparison between Enhanced Recovery After Surgery (ERAS) and conventional care after elective colorectal surgery. Am J Clin Nutr 2017; 106: 44-51 DOI: 10.3945/ajcn.116.148619.
• 43 McClave SA, Taylor BE, Martindale RG. et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016; 40: 159-211 DOI: 10.1177/0148607115621863.
• 44 Gillis C, Buhler K, Bresee L. et al. Effects of Nutritional Prehabilitation, With and Without Exercise, on Outcomes of Patients Who Undergo Colorectal Surgery: A Systematic Review and Meta-analysis. Gastroenterology 2018; 155: 391-410.e4 DOI: 10.1053/j.gastro.2018.05.012.
• 45 Moran J, Guinan E, McCormick P. et al. The ability of prehabilitation to influence postoperative outcome after intra-abdominal operation: A systematic review and meta-analysis. Surgery 2016; 160: 1189-1201 DOI: 10.1016/j.surg.2016.05.014.
• 46 Bhatnagar S, Mittal A, Gupta SK. et al. TWEAK causes myotube atrophy through coordinated activation of ubiquitin-proteasome system, autophagy, and caspases. J Cell Physiol 2012; 227: 1042-1051 DOI: 10.1002/jcp.22821.
• 47 Guttridge DC, Mayo MW, Madrid LV. et al. NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 2000; 289: 2363-2366 DOI: 10.1126/science.289.5488.2363.
• 48 Fukawa T, Yan-Jiang BC, Min-Wen JC. et al. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nat Med 2016; 22: 666-671 DOI: 10.1038/nm.4093.
• 49 Fleck A, Raines G, Hawker F. et al. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet 1985; 1: 781-784
• 50 Rozga J, Piatek T, Malkowski P. Human albumin: old, new, and emerging applications. Ann Transplant 2013; 18: 205-217 DOI: 10.12659/AOT.889188.
• 51 Lindemann K, Kok PS, Stockler M. et al. Enhanced Recovery After Surgery for Advanced Ovarian Cancer: A Systematic Review of Interventions Trialed. Int J Gynecol Cancer 2017; 27: 1274-1282 DOI: 10.1097/IGC.0000000000000981.