Network Meta-analysis for the Diagnostic Approach to Pathologic Nipple Discharge

Abstract

Pathologic nipple discharge (PND) is one of the most common breast-related complaints for referral because of its supposed association with breast cancer. The aim of this network meta-analysis (NMA) was to compare the diagnostic efficacy of ultrasound, mammogram, cytology, magnetic resonance imaging (MRI), and ductoscopy in patients with PND, as well as to determine the best diagnostic strategy to assess the risk of malignancy as cause for PND. Cochrane Library, PubMed, and Embase were searched to collect relevant literature from the inception of each of the diagnostic methods until January 27, 2020. The search yielded 1472 original citations, of which 36 studies with 3764 patients were finally included for analysis. Direct and indirect comparisons were performed using an NMA approach to evaluate the combined odd ratios and to determine the surface under the cumulative ranking curves (SUCRA) of the diagnostic value of different imaging methods for the detection of breast cancer in patients with PND. Additionally, a subgroup meta-analysis comparing ductoscopy to MRI when conventional imaging was negative was also performed. According to this NMA, sensitivity for detection of malignancy in patients with PND was highest for MRI (83%), followed by ductoscopy (58%), ultrasound (50%), cytology (38%), and mammogram (22%). Specificity was highest for mammogram (93%) followed by ductoscopy (92%), cytology (90%), MRI (76%), and ultrasound (69%). Diagnostic accuracy was the highest for ductoscopy (88%), followed by cytology (82%), MRI (77%), mammogram (76%), and ultrasound (65%). Subgroup meta-analysis (comparing ductoscopy to MRI when ultrasound and mammogram were negative) showed no significant difference in sensitivity, but ductoscopy was statistically significantly better with regard to specificity and diagnostic accuracy. The results from this NMA indicate that although ultrasound and mammogram may remain low-cost useful first choices for the detection of malignancy in patients with PND, ductoscopy outperforms most imaging techniques (especially MRI) and cytology.

Diagnostic Accuracy of Nipple Discharge Fluid Cytology: A Meta-Analysis and Systematic Review of the Literature

“…Moreover, this is the first review to interrogate the use of nipple smear cytology to detect both benign and malignant breast disease and to compare its performance with that of other breast imaging methods. The most recently published comparable review by Filipe et al 4 considers only malignant diagnostics and independently compares other imaging methods for which only histopathology is available. In addition, their study overlooked literature from which guidelines were drawn.…”

“…Clinical investigation of patients with pathologic nipple discharge (PND), defined as spontaneous single-duct and often blood-stained discharge, includes mammography, ultrasonography, magnetic resonance imaging (MRI), and even galactography to direct visualization of the ductal system ± ductal lavage. Although a recently published meta-analysis 4 compared the diagnostic accuracy of different imaging methods used for the investigation of PND, the capacity of cytology to interrogate PND comprehensively for both benign and malignant diagnoses is yet to be reviewed systematically.…”

Detection of breast cancer precursor lesions by autofluorescence ductoscopy

“…Ductoscopy has been used as a diagnostic modality to rule out malignancy, but while some studies reported a significant correlation [57,58], others found no specific data except for gross morphological abnormalities such as papillomas [22,[59][60][61]. A recent network meta-analysis showed that white ductoscopy has a high specificity (98%) but low sensitivity (44%) for the detection of breast cancer in patients with pathological nipple discharge with no radiological suspicion for malignancy [62]. Since intraductal lesions (such as papillomas) can be removed with relative ease and histopathologically analysed [18,46], autofluoresence might not be of added value in these cases.…”

Patient-reported outcomes of ductoscopy procedures for pathologic nipple discharge

“…A meta-analysis showed that ductoscopy has a sensitivity of 94% in detecting intraductal lesions of any type, but cannot reliably discriminate between benign and malignant lesions [46]. Another network meta-analysis showed that ductoscopy has a significantly higher diagnostic accuracy than MRI for the detection of malignancy in patients with PND and negative ultrasound and/or mammography [47]. Therefore, ductoscopy is more useful when conventional imaging is negative [26].…”