Validation of biomarkers and clinical scores for the detection of uterine leiomyosarcoma: a case-control study with an update of pLMS

Background: The diagnosis of rare uterine leiomyosarcoma (uLMS) remains a challenge given the high incidence rates of benign uterine tumors such as leiomyoma (LM). In the last decade, several clinical scores and blood serum markers have been proposed. The aim of this study is to validate and update the pLMS clinical scoring system, evaluating the accuracy of the scoring system by Zhang et al. and examining the discriminatory ability of blood markers such as serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR).

Methods: In a case-control study, 90 new uLMS from the DKSM consultation registry and 659 prospectively recruited LM cases from the Saarland University Hospital were used for validation. Welch's t-test and Hedges' g were used to evaluate blood markers and optimal thresholds and diagnostic odds ratios were calculated. Scoring systems were compared using receiver operating characteristics and proposed diagnostic cut-offs were reviewed. Missing values were imputed by random forest imputation to create the updated scoring system 'pLMS2' using penalized logistic regression based on the pooled data sets of 384 uLMS and 1485 LM.

Results: pLMS achieved an AUC of 0.97 on the validation data, but sensitivity and specificity varied at the proposed thresholds due to a shift in the score distributions. 43 uLMS and 578 LM were included in the comparison of pLMS with Zhang's scoring system, with pLMS being superior (AUC 0.960 vs 0.845). LDH, NLR, and PLR achieved a diagnostic odds ratios of 18.03, 8.64 and 4.81, respectively. pLMS2 is based on subscores for menopausal status interacting with age, tumor diameter, intermenstrual bleeding, hypermenorrhea, dysmenorrhea, postmenstrual bleeding, rapid tumor growth, and suspicious sonography.

Conclusions: Validation of the pLMS shows stable discriminatory ability as expressed by AUC, although caution should be taken with cut-off values, as sensitivity and specificity may vary. Data collection of the updated clinical score pLMS2 remains simple and convenient, with no additional cost. The proposed thresholds of 1.5 and 5.5 can be used as a guide to avoid unnecessary or inappropriate surgery and to make the use of further diagnostic measures cost-effective. LDH, NLR and PLR provide further evidence to differentiate uLMS from LM in conjunction with clinical data.