Ob/Gyn Epidemiology, Brigham and Women's Hospital, Boston, Massachusetts, USA
University of Michigan, Ann Arbor, Michigan, USA.
Int J Gynecol Cancer. 2021 May;31(5):733-743. doi: 10.1136/ijgc-2019-001103. Epub 2020 Jun 2.
Triaging patients with presumptive ovarian cancer to the appropriate specialist may improve survival. Therefore, there is increasing interest in complementary diagnostic markers to the standard serum CA125. In patients with pelvic masses, we examined the ability of epidemiologic variables and preoperative differential blood counts to improve detection of ovarian cancer over CA125 alone.
From pathology reports, patients were classified as having: epithelial ovarian cancer (n=743), including fallopian tube and primary peritoneal cancer, non-epithelial ovarian cancers (n=46), non-ovarian cancers (n=122), or benign disease (1,129). From women with epithelial ovarian cancer, we excluded those who received prior neoadjuvant chemotherapy (n=19). Women were also excluded if they did not have a serum CA125 or complete blood count measured within 180 days prior to surgery (n=1099) or did not have both tests within 90 days of each other (n=13). Categorizing patients by menopausal status, we calculated Pearson correlations between differential counts or ratios and CA125, and used t tests to identity univariate predictors of malignancy and stepwise logistic regression and likelihood ratio tests to create models best distinguishing epithelial ovarian cancer from benign disease.
337 women with epithelial ovarian cancer and 365 with benign disease were included in the analysis. Compared with cancers, women with benign disease had lower average: age, 52.5 versus 58.4 years (p<0.0001); serum CA125, 20 versus 239 U/mL (p<0.0001), neutrophil-to-lymphocyte ratio, 2.4 versus 3.5 (p<0.0001); and platelet-to-lymphocyte ratio, 158 versus 222 (p<0.0001); but greater average body mass index, 28.5 versus 26.8 kg/m (p=0.004), and lymphocyte-to-monocyte ratio, 5.6 versus 3.9 (p<0.0001). Correlations between counts and ratios and serum CA125 were seen in both epithelial ovarian cancer and benign disease groups and differed by menopausal status. In premenopausal women, a multivariate model including serum CA125, smoking, family history, lymphocytes, and monocytes performed similarly to the model with lymphocyte-to-monocyte ratio replacing counts. In postmenopausal women, a model including body mass index, parity, monocytes, and basophils performed similarly to the model replacing counts with platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio. Models including epidemiologic variables and either counts or ratios were better at fitting data than models with serum CA125 and menopausal status alone. A single model applying to all women overstated performance for premenopausal women and understated performance for postmenopausal women.
Epidemiologic variables and differential counts or ratios better distinguished between benign and malignant disease when compared with serum CA125 alone using separate models for pre- and postmenopausal women.
将疑似卵巢癌患者分诊至合适的专科医生可能会提高生存率。因此，人们越来越关注 CA125 以外的补充诊断标志物。在患有盆腔肿块的患者中，我们检查了流行病学变量和术前差异血液计数是否可以提高卵巢癌的检出率，而不仅仅是 CA125。
根据病理报告，患者被分为：上皮性卵巢癌（n=743），包括输卵管和原发性腹膜癌、非上皮性卵巢癌（n=46）、非卵巢癌（n=122）和良性疾病（1129）。对于上皮性卵巢癌患者，我们排除了那些接受过新辅助化疗的患者（n=19）。如果患者在手术前 180 天内没有测量血清 CA125 或全血计数（n=1099）或两者之间没有在 90 天内测量（n=13），则将其排除在外。通过绝经状态对患者进行分类，我们计算了差异计数或比率与 CA125 之间的 Pearson 相关性，并使用 t 检验来确定恶性肿瘤的单变量预测因素，并使用逐步逻辑回归和似然比检验来创建最佳区分上皮性卵巢癌和良性疾病的模型。
在分析中纳入了 337 名上皮性卵巢癌患者和 365 名良性疾病患者。与癌症相比，良性疾病患者的平均年龄较低：52.5 岁 vs 58.4 岁（p<0.0001）；血清 CA125 较低：20 U/ml vs 239 U/ml（p<0.0001），中性粒细胞与淋巴细胞比值较低：2.4 vs 3.5（p<0.0001）；血小板与淋巴细胞比值较低：158 vs 222（p<0.0001）；但平均体重指数较高：28.5 vs 26.8 kg/m（p=0.004），淋巴细胞与单核细胞比值较高：5.6 vs 3.9（p<0.0001）。上皮性卵巢癌和良性疾病组中均可见计数和比率与血清 CA125 之间的相关性，且与绝经状态有关。在绝经前妇女中，包括血清 CA125、吸烟、家族史、淋巴细胞和单核细胞的多变量模型与包含淋巴细胞与单核细胞比率替代计数的模型表现相似。在绝经后妇女中，包括体重指数、产次、单核细胞和嗜碱性粒细胞的模型与用血小板与淋巴细胞比率和淋巴细胞与单核细胞比率替代计数的模型表现相似。包括流行病学变量和计数或比率的模型在拟合数据方面优于仅包含血清 CA125 和绝经状态的模型。适用于所有女性的单一模型夸大了绝经前女性的表现，低估了绝经后女性的表现。
与单独使用血清 CA125 相比，使用单独的绝经前和绝经后妇女模型，流行病学变量和差异计数或比率可以更好地区分良性和恶性疾病。
