Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups

Our plain-English summary of Baseline predictors of negative and incomplete pleural cytology in patients with suspected pleural malignancy - Data supporting 'Direct to LAT' in selected groups, by S. Tsim, S. Paterson, D. Cartwright, et al (Lung Cancer, 2019).

The study

• Authors: S. Tsim, S. Paterson, D. Cartwright, C.J. Fong, L. Alexander, C. Kelly, J. Holme, M. Evison, K.G. Blyth
• Journal: Lung Cancer
• Published: 2019;133:123-129
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Negative effusion cytology is more common in certain forms of Malignant Pleural Effusion (MPE) and results in pathway delay. Local Anaesthetic Thoracoscopy (LAT) is extremely sensitive and safe but cannot be offered to all. A stratified pathway, including 'Direct to LAT' in selected cases could enhance patient experience but requires reliable baseline predictors of unhelpful cytology, including both negative (no malignant cells) and incomplete results (malignant cells identified but predictive markers failed), since pleural biopsies will be required in the latter for optimal management. This retrospective analysis of a prospective multi-centre study, sought to identify baseline features for pathway rationalization.

Materials And Methods: 363/638 (57%) of patients recruited to the DIAPHRAGM study (ISRCTN10079972) were included. Prospective data, including final diagnoses, asbestos exposure and fluid cytology results were supplemented by retrospective Computed Tomography (CT) and predictive marker reports. Independent predictors of negative and incomplete cytology were determined by multivariable logistic regression. Contingency tables were used to assess diagnostic value of cytology in associated phenotypes.

Results: 238/363 (66%) patients were diagnosed with MPE (18 tumour types). Fluid cytology was negative in 151/238 (63%) and independently associated with asbestos-exposure (Odds Ratio (OR) 5.34) and a malignant CT (OR 2.25). When both features were recorded the sensitivity and negative predictive value of fluid cytology were 19% (95% CI 11-30%) and 9% (95% CI 4-20%)), respectively. Cytology was incomplete in 34/238 (14%), i.e. 47% of positive cytology cases) but was not associated with any baseline feature. ORs for incomplete cytology in Ovarian, Breast, Renal and Lung Cancer were 83, 22, 21 and 9, respectively.

Conclusion: Negative cytology is extremely likely in patients with asbestos exposure and a malignant CT report. A 'Direct-to-LAT' approach may be appropriate in this setting. No baseline predictors of incomplete cytology were identified.

Copyright © 2019 Elsevier B.V. All rights reserved.

In plain English

This study re-examined 363 patients with suspected malignant pleural effusion (cancer-related fluid around the lung), recruited in Glasgow and South Manchester between December 2013 and December 2016 to a larger study, DIAPHRAGM. The authors looked for early features predicting unhelpful fluid tests. Of 238 finally diagnosed with malignant pleural effusion, 151 (63%) had no cancer cells detected in their fluid. Asbestos exposure (odds ratio 5.34, 95% CI 2.71 to 10.52) and a CT report suggesting cancer (odds ratio 2.25, 95% CI 1.25 to 4.06) were independently associated with these negative results. Of 64 patients with both features, 53 had malignant pleural effusion and 48 of these had negative fluid tests. Of the 64, 41 had mesothelioma, which fluid testing identified in no patient. In 34 of 73 positive cases needing tumour marker tests, the fluid sample was insufficient. The authors found no reliable predictor of this, though one table links asbestos exposure to lower odds of it. The authors concluded going directly to local anaesthetic thoracoscopy (camera-guided biopsy) may be appropriate for asbestos-exposed patients with a cancer-suggesting CT report.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of data from a prospective multi-centre diagnostic study (DIAPHRAGM), supplemented by retrospective review of CT reports and predictive marker results
• Who was studied: 363 of 466 potentially eligible patients with suspected malignant pleural effusion, recruited consecutively to DIAPHRAGM in Glasgow (404) and South Manchester (62) between December 2013 and December 2016. 238 were diagnosed with malignant pleural effusion: 92 with malignant pleural mesothelioma and 146 with secondary pleural malignancy.
• Exposure: History of asbestos exposure, recorded prospectively and analysed as a yes/no predictor alongside CT report and other clinical features. 161 patients were recorded as asbestos exposed. No fiber types, products or jobs are described.
• Main results:
  • Among 238 patients with proven malignant pleural effusion, fluid cytology was negative (no malignant cells identified) in 151 (63%).
  • On multivariable analysis, asbestos exposure was independently associated with negative fluid cytology: OR 5.34 (95% CI 2.71 to 10.52), p less than 0.0001.
  • A malignant CT report was also independently associated with negative fluid cytology: OR 2.25 (95% CI 1.25 to 4.06), p = 0.007.
  • In the 64 patients with both a malignant CT report and asbestos exposure, 53 had malignant pleural effusion and 48 of these (91%) had negative cytology. Of the 64, 41 (64%) had mesothelioma.
  • For this same group, the article reports a cytology sensitivity of 19% (95% CI 11 to 30%) and a negative predictive value of 9% (95% CI 4 to 20%). These figures conflict with the article's own counts (see text problems).
  • Cytology was positive in none of the mesothelioma patients in that group.
  • Predictive marker testing was recommended for 73 cases with malignant cytology. The fluid specimen was insufficient in 34 of these 73 (47%), equal to 14% of the 238 MPE patients.
  • The authors reported finding no reliable baseline features that predicted incomplete cytology.
  • Table 3, however, lists asbestos exposure on multivariable analysis as associated with a lower likelihood of incomplete cytology: OR 0.391 (95% CI 0.169 to 0.906), p = 0.028. The text states this feature failed to show an independent association.
  • A final diagnosis of ovarian cancer was strongly associated with incomplete cytology (OR 83.09, 95% CI 11.26 to 613.12). Marker testing failed in all 6 ovarian cancer cases with positive cytology. Breast (OR 22.43), renal (OR 21.25) and non-small cell lung cancer (OR 9.7) were also associated.
  • The volume of pleural fluid sent was not significantly associated with negative cytology.
  • Patients with negative cytology had a longer median time to diagnosis than those with positive cytology: 30 days (IQR 20 to 53) versus 13 days (IQR 9 to 17), p less than 0.0001.
• The authors' conclusion: The authors concluded that negative effusion cytology is extremely likely in patients with asbestos exposure and a malignant CT report, and that a 'Direct-to-LAT' approach may be appropriate in that setting. They found no reliable baseline predictors of incomplete cytology. They stated that 'Direct to LAT' may be justifiable in patients with a high pre-test probability of certain tumour types, but that this needs further study.
• Limitations the authors state:
  • CT reports and predictive marker results were reviewed retrospectively, introducing potential recall and omission bias.
  • Mesothelioma prevalence in the cohort was relatively high, so results are less generalisable to populations with limited asbestos exposure.
  • Patient numbers for the analysis of incomplete cytology were low, resulting in wide confidence intervals around the odds ratios.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Cytology, Pleural Effusion, Thoracoscopy, Diaphragm, Asbestos Exposure, Fluid Cytology, Odds Ratio, Lung Cancer.

Related studies

• The diagnostic performance of routinely acquired and reported computed tomography imaging in patients presenting with suspected pleural malignancy — S. Tsim, D.B. Stobo, et al. (2017)
• Early Contrast Enhancement: A novel magnetic resonance imaging biomarker of pleural malignancy — S. Tsim, C.A. Humphreys, et al. (2018)
• EZH2, a unique marker of malignancy in effusion cytology — H. Jiang, R. Gupta, et al. (2014)
• Pleural fluid cytology samples in cases of suspected lung cancer: An experience from a tertiary care centre — G. Kaur, R. Nijhawan, et al. (2017)
• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)
• Positive pleural cytology is an indicator for visceral pleural invasion in metastatic pleural effusions — M.E. Froudarakis, J. Plojoux, et al. (2018)

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