Objective. This study assesses the role of preoperative serum CA125 levels in the planning treatment options for women diagnosed with uterine cancer. Material and Method. Ninety five consecutive patients diagnosed with uterine cancer during a four-year period were identified. Age ranged from 35 to 89 years with a mean age of 69 years. The preoperative CA125 levels were dichotomised at 28?U/mL (using ROC analysis to identify the best discriminating threshold for 5-year survival). This level was then correlated with preoperative prognostic indicators: patient age, tumour grade, and histopathological tumour cell type. Survival data was plotted using Kaplan-Meier curves and analysed using the log-rank test. Univariate and multivariate analysis were performed to identify the predictors of overall survival. Results. The mean age of patients was 69 years (range: 35–89). On univariate analysis, the use of preoperative CA125 levels of greater or less than 28?U/mL correlated significantly with age , the grade of disease and unfavourable tissue type . This threshold CA125 level had a sensitivity of 75%, specificity of 76%, positive predictive value of 35% and negative predicative value of 96.25%, and a likelihood ratio of 3.12 for predicting nodal disease. Using a threshold of preoperative CA125 level of 28?U/mL (area under curve: 0.60) was also a significant predictor of 5-year survival (log-rank test, ). Using Cox multivariate survival analysis to identify predictive preoperative factors overall, unfavourable cell type was the strongest predictor of survival (Chi square?=?36.5, df?=?4, and ), followed by preoperative CA125 level (CA125?>?28?U/mL, ) and unfavourable preoperative grade ( ). Amongst patients with a favourable histological tissue type (endometrioid), preoperative CA125 levels predicted overall survival (Chi square?=?6.039, df?=?2, ); however unfavourable preoperative grade did not ( ). Overall, at five-year follow-up, while there were no deaths among the women with preoperative serum CA125 less than 12?U/mL, eleven of the twenty-three deaths (47.82%) in the study occurred in women with a preoperative CA125 more than 28?U/mL. Conclusions. A preoperative CA125 assay for women with uterine cancer is a relatively inexpensive, reproducible, and objective test which provides valuable information regarding the risk of metastatic disease and overall likelihood of long term survival. Patients with a low likelihood of metastatic/nodal disease (favourable tissue type and CA125 level?<?28?U/mL) and significant comorbidities may benefit from avoiding an extended
References
[1]
Statistics OfN, Cancer Statistics Registrations: Registrations of Cancer Diagnosed in 2008, England, 2010.
[2]
Unit WCIaS, Cancer Incidence in Wales 2005–2009, edited by Unit WCIaS, 2011.
[3]
ISD Online NHS Scotland IaSD, Cancer Incidence, Mortality and Survival data, 2010.
[4]
P. D. Sasieni, J. Shelton, N. Ormiston-Smith, C. S. Thomson, and P. B. Silcocks, “What is the lifetime risk of developing cancer: the effect of adjusting for multiple primaries,” British Journal of Cancer, vol. 105, no. 3, pp. 460–465, 2011.
[5]
M. P. Coleman, B. Rachet, L. M. Woods et al., “Trends and socioeconomic inequalities in cancer survival in England and Wales up to 2001,” British Journal of Cancer, vol. 90, no. 7, pp. 1367–1373, 2004.
[6]
W. J. Louwman, M. J. Aarts, S. Houterman, F. J. van Lenthe, J. W. W. Coebergh, and M. L. G. Janssen-Heijnen, “A 50% higher prevalence of life-shortening chronic conditions among cancer patients with low socioeconomic status,” British Journal of Cancer, vol. 103, no. 11, pp. 1742–1748, 2010.
[7]
S. M. Ueda, D. S. Kapp, M. K. Cheung et al., “Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths,” American Journal of Obstetrics and Gynecology, vol. 198, no. 2, pp. 218.e1–218.e6, 2008.
[8]
International Agency for Reseach on Cancer, GLOBOCAN 2008 v, IARC, European age-standardised rates calculated by the Statistical Information Team at Cancer Research UK, 2011.
[9]
W. Creasman, “Revised FIGO staging for carcinoma of the endometrium,” International Journal of Gynaecology & Obstetrics, vol. 105, no. 2, p. 109, 2009.
[10]
G. Plataniotis, M. Castiglione, and ESMO Guidelines Working Group, “Endometrial cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up,” Annals of Oncology, vol. 21, supplement 5, pp. v41–v5, 2010.
[11]
R. Woolas and D. Oram, “Current developments in the management of endometrial cancer,” in The Year Book of the RCOG, pp. 181–193, 1994.
[12]
J. V. Bokhman, “Two pathogenetic types of endometrial carcinoma,” Gynecologic Oncology, vol. 15, no. 1, pp. 10–17, 1983.
[13]
H. B. Salvesen, S. L. Carter, M. Mannelqvist et al., “Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 12, pp. 4834–4839, 2009.
[14]
W. T. Creasman, M. F. Kohler, F. Odicino, P. Maisonneuve, and P. Boyle, “Prognosis of papillary serous, clear cell, and grade 3 stage I carcinoma of the endometrium,” Gynecologic Oncology, vol. 95, no. 3, pp. 593–596, 2004.
[15]
C. P. Morrow, B. N. Bundy, R. J. Kurman et al., “Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a gynecologic oncology group study,” Gynecologic Oncology, vol. 40, no. 1, pp. 55–65, 1991.
[16]
C. L. Creutzberg, W. L. J. van Putten, C. C. Wárláin-Rodenhtiis et al., “Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the postoperative radiation therapy in endometrial carcinoma trial,” Journal of Clinical Oncology, vol. 22, no. 7, pp. 1234–1241, 2004.
[17]
R. Manfredi, P. Mirk, G. Maresca et al., “Local-regional staging of endometrial carcinoma: role of MR imaging in surgical planning,” Radiology, vol. 231, no. 2, pp. 372–378, 2004.
[18]
K. Kinkel, Y. Kaji, K. K. Yu et al., “Radiologic staging in patients with endometrial cancer: a meta-analysis,” Radiology, vol. 212, no. 3, pp. 711–718, 1999.
[19]
T. D. Barwick, A. G. Rockall, D. P. Barton, and S. A. Sohaib, “Imaging of endometrial adenocarcinoma,” Clinical Radiology, vol. 61, no. 7, pp. 545–555, 2006.
[20]
A. N. Gordon, A. C. Fleischer, B. S. Dudley et al., “Preoperative assessment of myometrial invasion of endometrial adenocarcinoma by sonography (US) and magnetic resonance imaging (MRI),” Gynecologic Oncology, vol. 34, no. 2, pp. 175–179, 1989.
[21]
E. Steiner, O. Eicher, J. Sagemüller et al., “Multivariate independent prognostic factors in endometrial carcinoma: a clinicopathologic study in 181 patients: 10 years experience at the department of obstetrics and gynecology of the mainz university,” International Journal of Gynecological Cancer, vol. 13, no. 2, pp. 197–203, 2003.
[22]
A. Sanjuán, T. Cobo, J. Pahisa et al., “Preoperative and intraoperative assessment of myometrial invasion and histologic grade in endometrial cancer: role of magnetic resonance imaging and frozen section,” International Journal of Gynecological Cancer, vol. 16, no. 1, pp. 385–390, 2006.
[23]
G. H. Eltabbakh, J. Shamonki, and S. L. Mount, “Surgical stage, final grade, and survival of women with endometrial carcinoma whose preoperative endometrial biopsy shows well-differentiated tumors,” Gynecologic Oncology, vol. 99, no. 2, pp. 309–312, 2005.
[24]
G. Vorgias, J. Lekka, M. Katsoulis, E. Varhalama, N. Kalinoglou, and T. Akrivos, “Diagnostic accuracy of prehysterectomy curettage in determining tumor type and grade in patients with endometrial cancer,” Medscape General Medicine, vol. 5, no. 4, 2003.
[25]
X. Wang, Z. Huang, W. Di, and Q. Lin, “Comparison of D&C and hysterectomy pathologic findings in endometrial cancer patients,” Archives of Gynecology and Obstetrics, vol. 272, no. 2, pp. 136–141, 2005.
[26]
A. Thanachaiviwat, C. Thirapakawong, C. Leelaphatanadit, and T. Chuangsuwanich, “Accuracy of preoperative curettage in determining tumor type and grade in endometrial cancer,” Journal of the Medical Association of Thailand, vol. 94, no. 7, pp. 766–771, 2011.
[27]
J. Mitchard and L. Hirschowitz, “Concordance of FIGO grade of endometrial adenocarcinomas in biopsy and hysterectomy specimens,” Histopathology, vol. 42, no. 4, pp. 372–378, 2003.
[28]
T. G. Stovall, G. J. Photopulos, W. M. Poston, F. W. Ling, and L. G. Sandles, “Pipelle endometrial sampling in patients with known endometrial carcinoma,” Obstetrics and Gynecology, vol. 77, no. 6, pp. 954–956, 1991.
[29]
A. G. Daniel and W. A. Peters, “Accuracy of office and operating room curettage in the grading of endometrial carcinoma,” Obstetrics and Gynecology, vol. 71, no. 4, pp. 612–614, 1988.
[30]
L. A. Hardesty, J. H. Sumkin, M. E. Nath et al., “Use of preoperative MR imaging in the management of endometrial carcinoma: cost analysis,” Radiology, vol. 215, no. 1, pp. 45–49, 2000.
[31]
I. B. Engelsen, I. M. Stefansson, L. A. Akslen, and H. B. Salvesen, “GATA3 expression in estrogen receptor α-negative endometrial carcinomas identifies aggressive tumors with high proliferation and poor patient survival,” American Journal of Obstetrics and Gynecology, vol. 199, no. 5, pp. 543.e1–543.e7, 2008.
[32]
I. B. Engelsen, I. Stefansson, L. A. Akslen, and H. B. Salvesen, “Pathologic expression of p53 or p16 in preoperative curettage specimens identifies high-risk endometrial carcinomas,” American Journal of Obstetrics and Gynecology, vol. 195, no. 4, pp. 979–986, 2006.
[33]
M. B. Silverman, P. C. Roche, R. M. Kho, G. L. Keeney, H. Li, and K. C. Podratz, “Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma,” Gynecologic Oncology, vol. 77, no. 1, pp. 1–7, 2000.
[34]
S. Oreskovic, D. Babic, D. Kalafatic, D. Barisic, and L. Beketic-Oreskovic, “A significance of immunohistochemical determination of steroid receptors, cell proliferation factor Ki-67 and protein p53 in endometrial carcinoma,” Gynecologic Oncology, vol. 93, no. 1, pp. 34–40, 2004.
[35]
J. Trovik, E. Wik, I. Stefansson et al., “Stathmin is superior to AKT and phospho-AKT staining for the detection of phosphoinositide 3-kinase activation and aggressive endometrial cancer,” Histopathology, vol. 57, no. 4, pp. 641–646, 2010.
[36]
I. B. Engelsen, I. M. Stefansson, R. Beroukhim et al., “HER-2/neu expression is associated with high tumor cell proliferation and aggressive phenotype in a population based patient series of endometrial carcinomas,” International Journal of Oncology, vol. 32, no. 2, pp. 307–316, 2008.
[37]
E. Wik, J. Trovik, O. E. Iversen et al., “Deoxyribonucleic acid ploidy in endometrial carcinoma: a reproducible and valid prognostic marker in a routine diagnostic setting,” American Journal of Obstetrics and Gynecology, vol. 201, no. 6, pp. 603.e1–603.e7, 2009.
[38]
R. C. Bast, T. L. Klug, E. S. John, et al., “A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer,” New England Journal of Medicine, vol. 309, no. 15, pp. 883–887, 1983.
[39]
R. C. Bast, M. Feeney, H. Lazarus, L. M. Nadler, R. B. Colvin, and R. C. Knapp, “Reactivity of a monoclonal antibody with human ovarian carcinoma,” The Journal of Clinical Investigation, vol. 68, no. 5, pp. 1331–1337, 1981.
[40]
A. Berchuck, A. P. Soisson, D. L. Clarke-Pearson et al., “Immunohistochemical expression of CA 125 in endometrial adenocarcinoma: correlation of antigen expression with metastatic potential,” Cancer Research, vol. 49, no. 8, pp. 2091–2095, 1989.
[41]
J. M. Niloff, T. L. Klug, E. Schaetzl, V. R. Zurawski, R. C. Knapp, and R. C. Bast, “Elevation of serum CA125 in carcinomas of the fallopian tube, endometrium, and endocervix,” American Journal of Obstetrics and Gynecology, vol. 148, no. 8, pp. 1057–1058, 1984.
[42]
M. Santala, A. Talvensaari-Mattila, and A. Kauppila, “Peritoneal cytology and preoperative serum CA 125 level are important prognostic indicators of overall survival in advanced endometrial cancer,” Anticancer Research, vol. 23, no. 3, pp. 3097–3103, 2003.
[43]
J. L. Powell, K. A. Hill, B. C. Shiro, S. J. Diehl, and W. H. Gajewski, “Preoperative serum CA-125 levels in treating endometrial cancer,” The Journal of Reproductive Medicine, vol. 50, no. 8, pp. 585–590, 2005.
[44]
Y. Todo, N. Sakuragi, R. Nishida et al., “Combined use of magnetic resonance imaging, CA 125 assay, histologic type, and histologic grade in the prediction of lymph node metastasis in endometrial carcinoma,” American Journal of Obstetrics and Gynecology, vol. 188, no. 5, pp. 1265–1272, 2003.
[45]
V. Kukura, G. Zovko, S. Ciglar et al., “Serum CA-125 tumor marker in endometrial adenocarcinoma,” European Journal of Gynaecological Oncology, vol. 24, no. 2, pp. 151–153, 2003.
[46]
S. Ginath, J. Menczer, Y. Fintsi, E. Ben-Shem, M. Glezerman, and I. Avinoach, “Tissue and serum CA125 expression in endometrial cancer,” International Journal of Gynecological Cancer, vol. 12, no. 4, pp. 372–375, 2002.
[47]
D. J. Dotters, “Preoperative CA 125 in endometrial cancer: is it useful?” American Journal of Obstetrics and Gynecology, vol. 182, no. 6, pp. 1328–1334, 2000.
[48]
H. Jhang, L. Chuang, P. Visintainer, and G. Ramaswamy, “CA 125 levels in the preoperative assessment of advanced-stage uterine cancer,” American Journal of Obstetrics and Gynecology, vol. 188, no. 5, pp. 1195–1197, 2003.
[49]
N. Takeshima, Y. Shimizu, S. Umezawa et al., “Combined assay of serum levels of CA125 and CA19-9 in endometrial carcinoma,” Gynecologic Oncology, vol. 54, no. 3, pp. 321–326, 1994.
[50]
A. Yildiz, H. Yetimalar, B. Kasap, et al., “Preoperative serum CA 125 level in the prediction of the stage of disease in endometrial carcinoma,” European Journal of Obstetrics, Gynecology, and Reproductive Biology, vol. 164, no. 2, pp. 191–195, 2012.
[51]
C.-H. Hsieh, C.-C. ChangChien, H. Lin et al., “Can a preoperative CA 125 level be a criterion for full pelvic lymphadenectomy in surgical staging of endometrial cancer?” Gynecologic Oncology, vol. 86, no. 1, pp. 28–33, 2002.
[52]
J. T. Soper, A. Berchuck, G. J. Olt, A. P. Soisson, D. L. Clarke-Pearson, and R. C. Bast, “Preoperative evaluation of serum CA 125, TAG 72, and CA 15-3 in patients with endometrial carcinoma,” American Journal of Obstetrics and Gynecology, vol. 163, no. 4, pp. 1204–1209, 1990.
[53]
H. S. Kim, C.-Y. Park, J.-M. Lee et al., “Evaluation of serum CA-125 levels for preoperative counseling in endometrioid endometrial cancer: a multi-center study,” Gynecologic Oncology, vol. 118, no. 3, pp. 283–288, 2010.
[54]
B. P. Goksedef, H. Gorgen, S. Y. Baran, M. Api, and A. Cetin, “Preoperative serum CA 125 level as a predictor for metastasis and survival in endometrioid endometrial cancer,” Journal of Obstetrics and Gynaecology Canada, vol. 33, no. 8, pp. 844–850, 2011.
[55]
I. Takac and B. Gorisek, “Serum CA 125 levels and lymph node metastasis in patients with endometrial cancer,” Wiener Klinische Wochenschrift, vol. 118, no. 2, supplement, pp. 62–65, 2006.
[56]
N. P. Koper, L. F. Massuger, C. M. Thomas, L. A. Kiemeney, and A. L. Verbeek, “Serum CA 125 measurements to identify patients with endometrial cancer who require lymphadenectomy,” Anticancer Research, vol. 18, no. 3, pp. 1897–1902, 1998.
[57]
A. K. Sood, R. E. Buller, R. A. Burger, J. D. Dawson, J. I. Sorosky, and M. Berman, “Value of preoperative CA 125 level in the management of uterine cancer and prediction of clinical outcome,” Obstetrics and Gynecology, vol. 90, no. 3, pp. 441–447, 1997.
[58]
S. M. Smith and M. S. Hoffman, “The role of vaginal hysterectomy in the treatment of endometrial cancer,” American Journal of Obstetrics and Gynecology, vol. 197, no. 2, pp. 202.e1–202.e7, 2007.
[59]
J. K. Chan, Y. G. Lin, B. J. Monk, K. Tewari, J. D. Bloss, and M. L. Berman, “Vaginal hysterectomy as primary treatment of endometrial cancer in medically compromised women,” Obstetrics and Gynecology, vol. 97, no. 5, part 1, pp. 707–711, 2001.
[60]
W. T. Creasman, C. P. Morrow, B. N. Bundy, H. D. Homesley, J. E. Graham, and P. B. Heller, “Surgical pathologic spread patterns of endometrial cancer: a gynecologic oncology group study,” Cancer, vol. 60, supplement 8, pp. 2035–2041, 1987.
[61]
G. A. Viani, B. F. Patia, A. C. Pellizzon et al., “High-risk surgical stage 1 endometrial cancer: analysis of treatment outcome,” Radiation Oncology, vol. 1, article 24, 2006.
[62]
E. L. Trimble, C. Kosary, and R. C. Park, “Lymph node sampling and survival in endometrial cancer,” Gynecologic Oncology, vol. 71, no. 3, pp. 340–343, 1998.
[63]
H. Watari, Y. Todo, M. Takeda, Y. Ebina, R. Yamamoto, and N. Sakuragi, “Lymph-vascular space invasion and number of positive para-aortic node groups predict survival in node-positive patients with endometrial cancer,” Gynecologic Oncology, vol. 96, no. 3, pp. 651–657, 2005.
[64]
C. V. Lutman, L. J. Havrilesky, J. M. Cragun et al., “Pelvic lymph node count is an important prognostic variable for FIGO stage I and II endometrial carcinoma with high-risk histology,” Gynecologic Oncology, vol. 102, no. 1, pp. 92–97, 2006.
[65]
Y. Yokoyama, H. Maruyama, S. Sato, and Y. Saito, “Indispensability of pelvic and paraaortic lymphadenectomy in endometrial cancers,” Gynecologic Oncology, vol. 64, no. 3, pp. 411–417, 1997.
[66]
M. N. Barnes and L. C. Kilgore, “Complete surgical staging of early endometrial adenocarcinoma: optimizing patient outcomes,” Seminars in Radiation Oncology, vol. 10, no. 1, pp. 3–7, 2000.
[67]
K. W. Lo, T. H. Cheung, M. Y. Yu, S. F. Yim, and T. K. Chung, “The value of pelvic and para-aortic lymphadenectomy in endometrial cancer to avoid unnecessary radiotherapy,” International Journal of Gynecological Cancer, vol. 13, no. 6, pp. 863–869, 2003.
[68]
T. O. Wilson, K. C. Podratz, T. A. Gaffey, G. D. Malkasian, P. C. O'Brien, and J. M. Naessens, “Evaluation of unfavorable histologic subtypes in endometrial adenocarcinoma,” American Journal of Obstetrics and Gynecology, vol. 162, no. 2, pp. 418–426, 1990.
[69]
T. W. Burke, P. B. Heller, J. E. Woodward, S. A. Davidson, W. J. Hoskins, and R. C. Park, “Treatment failure in endometrial carcinoma,” Obstetrics and Gynecology, vol. 75, no. 1, pp. 96–101, 1990.
[70]
P. G. Rose, R. M. Sommers, F. R. Reale, R. E. Hunter, L. Fournier, and B. E. Nelson, “Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma,” Obstetrics and Gynecology, vol. 84, no. 1, pp. 12–16, 1994.
[71]
J. M. Duk, J. G. Aalders, G. J. Fleuren, and H. W. de Bruijn, “CA 125: a useful marker in endometrial carcinoma,” American Journal of Obstetrics and Gynecology, vol. 155, no. 5, pp. 1097–1102, 1986.
[72]
B. Patsner, W. J. Mann, H. Cohen, and M. Loesch, “Predictive value of preoperative serum CA 125 levels in clinically localized and advanced endometrial carcinoma,” American Journal of Obstetrics and Gynecology, vol. 158, no. 2, pp. 399–402, 1988.
[73]
P. L. Cherchi, S. Dessole, G. A. Ruiu et al., “The value of serum CA 125 and association CA 125/CA 19-9 in endometrial carcinoma,” European Journal of Gynaecological Oncology, vol. 20, no. 4, pp. 315–317, 1999.
[74]
T. Alagoz, R. E. Buller, M. Berman, B. Anderson, A. Manetta, and P. Disaia, “What is a normal CA125 level?” Gynecologic Oncology, vol. 53, no. 1, pp. 93–97, 1994.
[75]
A. Sebastianelli, M. C. Renaud, J. Grégoire, M. Roy, and M. Plante, “Preoperative CA 125 tumour marker in endometrial cancer: correlation with advanced stage disease,” Journal of Obstetrics and Gynaecology Canada, vol. 32, no. 9, pp. 856–860, 2010.