Impact of Detecting Occult Pathologic Nodal Disease During Resection for Malignant Pleural Mesothelioma

Our plain-English summary of Impact of Detecting Occult Pathologic Nodal Disease During Resection for Malignant Pleural Mesothelioma, by V. Verma, R.E. Wegner, J.M. Stahl, et al (Clinical Lung Cancer, 2020).

The study

• Authors: V. Verma, R.E. Wegner, J.M. Stahl, A.R. Barsky, D. Raghavan, T.E. Busquets, B.S. Hoppe, S. Grover, J.S. Friedberg, C.B. Simone
• Journal: Clinical Lung Cancer
• Published: 2020;21(4):e274-e285
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Lymph node (LN) involvement is a poor prognostic factor for malignant pleural mesothelioma (MPM). However, to our knowledge, postresection outcomes of node-negative (cN0/pN0), occult pathologic nodal disease (cN0/pN+), and clinical node-positive disease (cN+) have not been compared to date.

Patients And Methods: The National Cancer Data Base was queried for newly diagnosed, resected MPM with known clinical/pathologic LN information. Three cohorts were compared: cN0/pN0, cN+, and cN0/pN+. Multivariable logistic regression examined predictors of pathologic nodal upstaging. Kaplan-Meier analysis with propensity matching assessed overall survival (OS); multivariate Cox proportional hazards modeling examined predictors thereof.

Results: Of 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) cN+, and 225 (16%) cN0/pN+ disease. Median follow-up was 29 months. In patients with cN0 disease, factors associated with pathologic nodal upstaging were younger age, greater number of examined LNs, and nonsarcomatoid histology (P < .05 for all). Relative to pN0 cases, occult LN involvement (65% being pN2) was associated with 51% higher hazard of mortality on multivariate analysis (P = .005). Following propensity matching, the OS of cN0/pN+ was similar to cN+ cases (P = .281). On multivariate analysis, the number of involved LNs (continuous variable, P = .013), but not nodal tumor, node, metastasis (TNM) classification or LN ratio (P > .05 for both), was associated with OS.

Conclusion: Detecting occult nodal disease during resection for cN0 MPM is associated with poorer prognosis, with similar survival as cN+ cases, underscoring the importance of routine preoperative pathologic nodal assessment for potentially resectable MPM. The number of involved LNs (rather than current location-based classification) may provide more robust prognostic stratification for future TNM staging.

Copyright © 2020 Elsevier Inc. All rights reserved.

In plain English

This retrospective study used the US National Cancer Data Base (2004 to 2013) to look at 1369 patients with newly diagnosed malignant pleural mesothelioma, without distant spread, who had surgery. Asbestos exposure was not reported. Patients were grouped by lymph node findings. 687 had no node involvement found before or after surgery. 457 had node involvement seen before surgery. 225 had no node involvement seen before surgery but had cancer found in nodes removed during surgery ("occult" disease). Compared with the no-node group, occult node disease was associated with a higher hazard of death (hazard ratio 1.507, 95% confidence interval 1.134-2.002). Node involvement seen before surgery was also associated with a higher hazard (1.361, 1.036-1.788). After statistical matching, survival was similar in the occult and seen-before-surgery groups. A higher number of cancer-containing nodes was associated with poorer survival. Node-location staging and the share of nodes involved were not. The authors concluded that occult node disease is associated with poorer prognosis, and they supported routine node testing before surgery. They noted that the database lacked information on preoperative staging tests.

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 a national cancer registry (National Cancer Data Base), using multivariable logistic regression, Kaplan-Meier survival analysis with 1:1 propensity matching, and multivariable Cox proportional hazards modeling
• Who was studied: 1369 patients in the US National Cancer Data Base with newly diagnosed, nonmetastatic malignant pleural mesothelioma, diagnosed 2004-2013. All had surgical resection and known clinical and pathologic lymph node status. 687 (50%) were cN0/pN0 (no node involvement found clinically before surgery or on pathology after surgery). 457 (33%) were cN+ (node disease seen clinically before surgery). 225 (16%) were cN0/pN+ (no node disease seen clinically, but nodal disease found on pathology after surgery).
• Exposure: Not asbestos. The study compared lymph node status groups among patients who had extrapleural pneumonectomy or pleurectomy/decortication. Asbestos exposure is not reported in the article.
• Main results:
  • Of the 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) had cN+, and 225 (16%) had cN0/pN+ disease. 65% of the cN0/pN+ group had pN2 disease.
  • Among patients with no node disease seen before surgery (cN0), older age and more advanced T classification were associated with a lower likelihood of finding occult node disease. Nonsarcomatoid histology and more lymph nodes dissected were associated with a higher likelihood (P less than .05 for each).
  • In unadjusted analysis, median survival was 17.5 months (95% CI 16.2-19.4) for cN0/pN0 patients and 16.3 months (95% CI 13.9-21.2) for cN0/pN+ patients (P = .740). Propensity matching of these two groups could not be completed because of persistent imbalances.
  • In a subgroup analysis, cN0/pN0 patients had higher overall survival than cN0/pN+ patients (P less than .001) when 14 or more lymph nodes were dissected. The difference was equivocal (P = .214) when fewer than 14 were removed.
  • Median survival in the cN+ group was 13.4 months (95% CI 12.5-14.7). Before matching, the cN0/pN+ group had higher overall survival than the cN+ group (P = .040). This difference did not persist after propensity matching (P = .281).
  • In the multivariate Cox model, compared with cN0/pN0, the hazard ratio for death was 1.507 (95% CI 1.134-2.002, P = .005) for cN0/pN+ and 1.361 (95% CI 1.036-1.788, P = .027) for cN+.
  • The number of positive lymph nodes, analyzed as a continuous variable, was associated with overall survival (hazard ratio 1.040, 95% CI 1.008-1.073, P = .013). The location-based nodal classification was not predictive. The lymph node ratio was not significant (P = .816).
  • Other factors associated with poorer overall survival in the multivariate model were older age, male gender, treatment at community facilities, nonepithelioid histology, and not receiving chemotherapy or radiotherapy.
• The authors' conclusion: The authors concluded that discovering occult nodal disease in malignant pleural mesothelioma is associated with poorer prognosis and with survival similar to clinically node-positive disease. They wrote that this supports guidelines for routine preoperative pathologic nodal assessment in surgical candidates. They also suggested, as hypothesis-generating, that the number of involved nodes may be more prognostic than node location for future staging.
• Limitations the authors state:
  • The database lacked information on preoperative staging by PET scan and on preoperative pathologic nodal assessment, so some truly clinically node-positive patients may have been classified as cN0/pN+.
  • Imbalances between the cN0/pN0 and cN0/pN+ groups could not be adequately corrected by propensity matching.
  • The 14-node threshold used to define a thorough dissection is questionable, because there is no recommended optimal node yield in malignant pleural mesothelioma.
  • The database does not provide the specific locations or stations of lymph nodes.
  • The database lacks performance status, pulmonary function tests, chemotherapy agents and salvage therapies, any of which could confound the results. It also lacks cancer-specific survival.
  • Only Commission on Cancer-accredited facilities contribute data, so the findings may not represent the entire US population.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Node-negative, Overall Survival, Histology, Multivariate Analysis, Metastasis, Prognosis, TNM Staging.

Related studies

• Survival by Histologic Subtype of Malignant Pleural Mesothelioma and the Impact of Surgical Resection on Overall Survival — V. Verma, C.A. Ahern, et al. (2018)
• Malignant Mesothelioma of the Tunica Vaginalis Testis: Outcomes Following Surgical Management Beyond Radical Orchiectomy — P. Recabal, B. Rosenzweig, et al. (2017)
• CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative — D. Roife, B.D. Powers, et al. (2020)
• Extrapleural pneumonectomy in the treatment of epithelioid malignant pleural mesothelioma: novel prognostic implications of combined N1 and N2 nodal involvement based on experience in 529 patients — D.J. Sugarbaker, W.G. Richards, et al. (2014)
• Treatment of malignant pleural mesothelioma with chemotherapy preceding versus after surgical resection — V. Verma, C.A. Ahern, et al. (2019)
• Retroperitoneal lymph node dissection in malignant mesothelioma of tunica vaginalis testis — J.J. Smith, M.J. Malone, et al. (1990)

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