The ovarian cancers in geriatric population: the validity of inflammatory markers, malignancy risk indices 1, 2, 3, 4, and CA-125 levels in malignancy discrimination of adnexal masses

Purpose: To investigate the predictive value of the Risk of Malignancy Index (RMI), CA-125, and inflammatory markers in discriminating ovarian cancers (OCs). Materials and Methods: The postmenopausal (PM) women (n = 139) with adnexal masses who underwent surgery were included. The predictive value of CA-125, RMI (1, 2, 3, and 4) and inflammatory markers [neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR)] were calculated in geriatric (G) and non-geriatric women. Results: OCs had significantly increased NLR and PLR. RMI models were highly reliable in PM (Kappa: 0.642-0.715; AUC: 0.907-0.934). CA-125 measurement alone had good accuracy and moderate reliability in PM (kappa: 0.507-0.587), excellent accuracy and moderate reliability in G, NLR, and PLR predicting OCs, showed fair agreement in the PM, while PLR had a moderate agreement with G. Conclusion: RMI algorithms were the best models for malignancy prediction. However, the rise of PLR and CA-125 levels in a G population may be used as referring adnexal masses to gynecologic oncologists.

Ovarian cancers; Risk of malignancy risk index; Adnexal masses; CA-125; cancer screening; Neutrophil lymphocyte ratio; Platelet lymphocyte ratio; Geriatric; Menopause.

[1] United Nations, Department of Economic and Social Affairs, Population

Division.: “World Population Ageing 2013”. ST/ESA/

SER.A/348. New York: United Nations Publication, 2013.

[2] Trillsch F., Woelber L., Eulenburg C., Braicu I., Lambrechts

S., Chekerov R., et al.: “Treatment reality in elderly patients with advanced

ovarian cancer: a prospective analysis of the OVCADconsortium”.

J. Ovarian Res., 2013, 6, 42.

[3] Su Z, Graybill WS, Zhu Y.: “Detection and monitoring of ovarian

cancer”. Clin. Chim. Acta, 2013, 415, 341.

[4] Jacobs I., Bast R.C. Jr.: “ The CA-125 tumor-associated antigen: a review

of the literature”. Hum. Reprod., 1989, 4, 1.

[5] Jacobs I., Oram D., Fairbanks J., Turner J., Frost C., Grudzinskas

J.G.: “A risk of malignancy incorporating CA-125, ultrasound and

menopausal status fort he accurate preoperative diagnosis of ovarian

cancer”. Br. J. Obstet. Gynecol., 1990, 97, 922.

[6] Tingulstad S., Hagen B., Skjeldestad F.E., Onsrud M., Kiserud T.,

Halvorsen T., et al.: “Evaluation of risk of malignancy index based

on serum CA-125, ultrasound findings and menopausal status in the

preoperative diagnosis of pelvic masses”. Br. J. Obstet. Gynecol.,

1996, 102, 826.

[7] Tingulstad S., Hagen B., Skjeldestad F.E., Halvorsen T., Nustad K.,

Onsrud M.: “The risk of malignancy index to evaluate potential ovarian

cancers in local hospitals”. Obstet. Gynecol., 1999, 93, 448.

[8] Yamamoto Y., Yamada R., Oguri H., Maeda N., Fukaya T.: “ Comparison

of four malignancy risk indices in the preoperative evaluation

of patients with pelvic masses”. Eur. J. Obstet. Gynecol. Reprod.

Biol., 2009, 144, 163.

[9] Terzic M., Dotlic J., Likic I., Brndusic N., Pilic I., Ladjevic N., et

al.: “Risk of malignancy index validity assessment in premenopausal

and postmenopausal women with adnexal tumors”. Taiwan J. Obstet.

Gynecol., 2013, 52, 253.

[10] Sayasneh A., Wynants L., Preisler J., Kaijser J., Jonhsın S., Stalder C.,

et al.: “Multicentre external validation of IOTA prediction models and

RMI by operators with varied training”. Br. J. Cancer, 2013, 108, 2448.

[11] Kaijser J., Sayasneh A., Van Hoorde K.,Ghaem-Maghami S., Bourne

T., Timmerman D., Van Calster B.: “Presurgical diagnosis of adnexal

tumors using mathematical models and scoring systems: a systematic

review and meta-analysis”. Hum. Reprod. Update, 2014, 20, 449.

[12] Geomini P., Kruitwagen R., Bremer G.L., Cnossen J., Mol B.W.:

“The accuracy of risk scores in predicting ovarian malignancy: a systematic

review”. Obstet. Gynecol., 2009, 113, 384.

[13] Donskov F.: “Immunomonitoring and prognostic relevance of neutrophils

in clinical trials”. Semin. Cancer Biol., 2013, 23, 200.

[14] Balkwill F., Mantovani A.: “Inflammation and cancer: back to Virchow?

” Lancet, 2001, 357, 539.

[15] Coussens L.M., Werb Z.: “Inflammation and cancer”. Nature, 2002,

420, 860.

[16] Salazar-Onfray F., Lopez M.N., Mendoza-Naranjo A.: “Paradoxical

effects of cytokines in tumor immune surveillance and tumor escape”.

Cytokine Growth Factor Rev., 2007, 18, 171–182.

[17] Stone R.L., Nick A.M., McNeish I.A., Balkwill F., Han H.D., Bottsford-

Miller J., et al.: “Paraneoplastic thrombocytosis in ovarian cancer”.

N. Engl. J. Med., 2012, 366, 610.

[18] Krenn-Pilko S., Langsenlehner U., Thurner E.M., Stojakovic

T., Pichler M., Gerger A., et al.: “The elevated preoperative plateletto-

lymphocyte ratio predicts poor prognosis in breast cancer patients”.

Br. J. Cancer, 2014, 110, 2524.

[19] Templeton A.J., McNamara M.G., Šeruga B., Vera-Badillo F.E.,

Aneja P., Ocaña A., et al.: “Prognostic role of neutrophil-tolymphocyte

ratio in solid tumors: a systematic review and metaanalysis”.

J. Natl. Cancer Inst., 2014, 106, dju124.

[20] Templeton A.J., Ace O., McNamara M.G., Al-Mubarak M., Vera-

Badillo F.E., Hermanns T., et al.: “Prognostic role of platelet to

lymphocyte ratio in solid tumors: a systematic review and metaanalysis”.

Cancer Epidemiol. Biomarkers Prev., 2014, 23, 1204.

[21] Cho H., Hur H.W., Kim S.W., Kim S.H., Kim J.H., Kim Y.T., Lee K.:

“Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial

ovarian cancer and predicts survival after treatment”. Cancer Immunol

Immunother., 2009, 58, 15.

[22] Thavaramara T., Phaloprakarn C., Tangjitgamol S., Manusirivithaya

S.: “Role of neutrophil to lymphocyte ratio as a prognostic indicator

for epithelial ovarian cancer”. J. Med. Assoc. Thai, 2011, 94, 871.

[23] Yildirim M., Demir Cendek B., Filiz Avsar A.: “Differentiation between

benign and malignant ovarian masses in the preoperative period

using neutrophil-to-lymphocyte and platelet-tolymphocyte

ratios”. Mol. Clin. Oncol., 2015, 3, 317.

[24] Asher V., Lee J., Innamaa A., Bali A.: “Preoperative platelet lymphocyte

ratio as an independent prognostic marker in ovarian cancer”.

Clin. Transl. Oncol., 2011, 13, 499.

[25] Raungkaewmanee S., Tangjitgamol S., Manusirivithaya S., Srijaipracharoen

S., Thavaramara T.: “Platelet to lymphocyte ratio as a

prognostic factor for epithelial ovarian cancer”. J. Gynecol.

Oncol., 2012, 23, 265.

[26] Kokcu A., Kurtoglu E., Celik H., Tosun M., Malatyalıoglu E.,

Ozdemir A.Z.: “ May the platelet to lymphocyte ratio be a prognostic

factor for epithelial ovarian cancer?” Asian Pac. J. Cancer Prev.,

2014, 15, 9781.

[27] American College of Obstetricians and Gynecologists.: “ACOG

Committee Opinion: number 280, December 2002. The role of the

generalist obstetrician-gynecologist in the early detection of ovarian

cancer”. Obstet. Gynecol., 2002, 100, 14, 13.

[28] Rufford B.D., Jacobs I.J. : “Green-top Guideline No. 34. Ovarian cysts

in postmenopausal women”. London, UK: Royal College of Obstetricians and Gynaecologists, 2003. Available at: http:// www.rcog.org.uk/files/rcog-corp/GTG3411022011.pdf

[29] Suh D.H., Kim H.S., Chung H.H., Kim J.W., Park N.H., Song Y.S., Kang S.B.: “Preoperative systemic inflammatory response markers in predicting lymph node metastasis in endometrioid endometrial adenocarcinoma”. Eur. J. Obstet. Gynecol. Reprod. Biol., 2012, 162, 206.

[30] Lee Y.Y., Choi C.H., Kim H.J., Kim T.J., Lee J.W., Lee J.H., et al.: “Pretreatment neutrophil: lymphocyte ratio as a prognostic factor in cervical carcinoma”. Anticancer Res., 2012, 32, 1555.

[31] Kwon H.C., Kim S.H., Oh S.Y., Lee S., Lee J.H., Choi H.J., et al.: “Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer”. Biomarkers, 2012, 17, 216.

[32] Smith R.A., Ghaneh P., Sutton R., Raraty M., Campbell F., Neoptolemos J.P.: “Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet-lymphocyte ratio”. J. Gastrointest. Surg., 2008, 12, 1422.