Leukocytosis and thrombocytosis as prognostic factors for women with uterine cervical cancer

Purpose of Investigation: The aim of this study was to evaluate whether leukocytosis and thrombocytosis prior to treatment was associated with the prognosis of women with uterine cervical cancer. Materials and Methods: The authors assessed 2,267 women who were diagnosed as having FIGO Stages I-IV uterine cervical cancer and were followed up for at least five years. The age, clinical stage, histology, leukocytosis, and thrombocytosis at the initial diagnosis were evaluated for overall survival (OS). Results: Leukocytosis and thrombocytosis were identified in 315 and in 134 women, respectively. Fifty-eight had both conditions. Multivariable analysis revealed that age [hazard ratio (HR) 1.7, p < 0.001], advanced FIGO Stage (4.8, p < 0.001), histology (2.0, p < 0.001), leukocytosis (1.5, p < 0.01), and thrombocytosis (2.0, p < 0.01) were independent factors for decreased OS. OS of women with both thrombocytosis and leukocytosis was the worst (p < 0.01). Conclusion: Leukocytosis and thrombocytosis were independently associated with decreased OS in women with uterine cervical cancer.

Cervical cancer; Leukocytosis; Thrombocytosis; Prognosis.

[1] Boyce J.G., Fruchter R.G., Nicastri A.D., DeRegt R.H., Ambiavagar P.C., Reinis M., et al.: “Vascular invasion in Stage I carcinoma of the cervix”. Cancer, 1984, 53, 1175.

[2] Zreik T.G., Chambers J.T., Chambers S.K.: “Parametrial involvement, regardless of nodal status: a poor prognostic factor for cervical cancer”. Obstet. Gynecol., 1996, 87, 741.

[3] Delgado G., Bundy B., Zaino R., Sevin BU., Creasman WT., Major F.: “Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study”. Gynecol Oncol., 1990, 38, 352.

[4] Sevin B.U.., Lu Y., Bloch D.A., Nadji M., Koechli O.R., Averette H.E.: “Surgically defined prognostic parameters in patients with early cervical carcinoma. Amultivariate survival tree analysis”. Cancer, 1996, 78, 1438.

[5] Kamura T., Tsukamoto N., Tsuruchi N., Saito T., Matsuyama T., Akazawa K., Nakano H.: “Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy”. Cancer, 1992, 69, 181.

[6]Estape R.E., Angioli R., Madrigal M., Janicek M., Gomez C., Penalver M., Averette H.: “Close vaginal margins as a prognostic factor after radical hysterectomy”. Gynecol. Oncol., 1998, 68, 229.

[7]Maione P., Rossi A., Di Maio M., Gridelli C.: “Tumor-related leukocytosis and chemotherapy-induced neutropenia: linked or independent prognostic factors for advanced non-small cell lung cancer? ”. Lung Cancer., 2009, 66, 8.

[8]Holgersson G., Hoye E., Bergqvist M., Ekman S., Nyman J., Helsing M.et al.: “Swedish Lung Cancer Radiation Study Group: predictive value of age at diagnosis for radiotherapy response in patients with non-small cell lung cancer”. Acta Oncol., 2012, 51, 759.

[9]Mabuchi S., Matsumoto Y., Isohashi F., Yoshioka Y., Ohashi H., Morii E.et al.: “Pretreatment leukocytosis is an indicator of poor prognosis in patients with cervical cancer”. Gynecol Oncol., 2011, 122, 25.

[10]Mabuchi S., Matsumoto Y., Kawano M., Minami K., Seo Y., Sasano T., et al.: “Uterine cervical cancer displaying tumor-related leukocytosis: a distinct clinical entity with radioresistant feature”. J. Natl. Cancer Inst., 2014, 106, 147.

[11] Qiu M.Z., Xu R.H., Ruan D.Y., Li Z.H., Luo H.Y., Teng K.Y., et al.: “Incidence of anemia, leukocytosis, and thrombocytosis in patients with solid tumors in China”. Tumour Biol., 2010, 31, 633.

[12] Mabuchi S., Matsumoto Y., Hamasaki T., Kawano M., Hisamatsu T., Mutch DG., Kimura T.: “Elevated white blood cell count at the time of recurrence diagnosis is an indicator of short survival in patients with recurrent cervical cancer”. Int. J. Gynecol. Cancer, 2012, 22, 1545.

[13] Levin J., Conley C.L.: “Thrombocytosis associated with malignant disease”. Arch. Intern. Med., 1964, 114, 497.

[14] Cheng J., Zeng Z., Ye Q., Zhang Y., Yan R., Liang C., et al.: “The association of pretreatment thrombocytosis with prognosis and clinicopathological significance in cervical cancer: a systematic review and meta-analysis”. Oncotarget, 2017, 8, 24327.

[15] Schernberg A., Huguet F., Moureau-Zabotto L., Chargari C., Rivin Del Campo E., MichelSchlienger M., et al.: “External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.”. Radiother Oncol., 2017, 124, 110.

[16] Schernberg A., Moureau-Zabotto L., Rivin Del Campo E., Escande A., Ducreux M., Nguyen F., et al.: “Leukocytosis and neutrophilia predict outcome in locally advanced esophageal cancer treated with definitive chemoradiation”. Oncotarget, 2017, 8, 11579.

[17] Kozak M.M., von Eyben R., Pai J.S., Anderson E.M., Welton M.L., Shelton A.A., et al.: “The Prognostic Significance of Pretreatment Hematologic Parameters in Patients Undergoing Resection for Colorectal Cancer”. Am. J. Clin. Oncol., 2017, 40, 405.

[18] 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.

[19] Matsumoto Y., Mabuchi S., Muraji M., Morii E., Kimura T.: “Squamous cell carcinoma of the uterine cervix producing granulocyte colony-stimulating factor: a report of 4 cases and a review of the literature”. Int. J. Gynecol. Cancer, 2010, 20, 417.

[20] Gutschalk C.M., Herold-Mende C.C., Fusenig N.E., Mueller M.M.: “Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor promote malignant growth of cells from head and neck squamous cell carcinomas in vivo”. Cancer Res., 2006, 66, 8026.

[21] Labelle M., Begum S., Hynes R.O.: “Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis”. Cancer Cell, 2011, 20, 576.

[22] Srivani R., Nagarajan B.: “A prognostic insight on in vivo expression of interleukin-6 in uterine cervical cancer”. Int. J. Gynecol. Cancer, 2003, 13, 331.