Impact of guideline therapy on survival of patients with stage I-III epithelioid mesothelioma

Our plain-English summary of Impact of guideline therapy on survival of patients with stage I-III epithelioid mesothelioma, by D.Z. Liou, Y. Wang, P. Bhandari, et al (Journal of Thoracic Disease, 2023).

The study

• Authors: D.Z. Liou, Y. Wang, P. Bhandari, J.B. Shrager, N.S. Lui, L.M. Backhus, M.F. Berry
• Journal: Journal of Thoracic Disease
• Published: 2023;15(12):6661-6673
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Modern treatment guidelines recommend multimodal therapy with at least chemotherapy and surgery for patients with potentially resectable epithelioid mesothelioma. This study evaluated guideline compliance for patients with stage I-III epithelioid mesothelioma and tested the hypothesis that guideline-concordant therapy improved survival.

Methods: The National Cancer Database was queried for patients with stage I-III epithelioid malignant pleural mesothelioma between 2004 and 2016. The impact of therapy was evaluated using logistic regression, Kaplan-Meier analysis, Cox-proportional hazards analysis, and propensity-scoring methods.

Results: During the study period, guideline-concordant therapy was used in 677 patients (19.1%), and 2,857 patients (80.8%) did not have guideline-concordant therapy. Younger age, being insured, living in a census tract with a higher income, clinical stage, and being treated at an academic or research program were all predictors of receiving guideline-concordant therapy in multivariable analysis. Guideline-concordant therapy yielded improved median survival [24.7 (22.4-26.1) vs. 13.7 (13.2-14.4) months] and 5-year survival [17.7% (14.7-21.3%) vs. 8.0% (7.0-9.3%)] (P<0.001), and continued to be associated with better survival in both multivariable analysis and propensity-matched analysis. In the patients who received guideline therapy, median survival [24.9 (21.9-27.2) vs. 24.5 (21.7-28.1) months] and 5-year survival [14.9% (10.9-20.2%) vs. 20.1% (16.0-25.4%)] was not significantly different between patients who underwent induction (n=304) versus adjuvant (n=373) chemotherapy (P=0.444).

Conclusions: Guideline-concordant therapy for potentially resectable epithelioid mesothelioma is associated with significantly improved survival but used in a minority of patients. The timing of chemotherapy with surgery in this study did not have a significant impact on overall survival.

2023 Journal of Thoracic Disease. All rights reserved.

In plain English

This study concerned mesothelioma treatment, not asbestos exposure. The authors used the US National Cancer Database to find 3,534 patients diagnosed from 2004 to 2016 with stage I–III epithelioid malignant pleural mesothelioma. Guideline-concordant therapy meant cancer-directed surgery plus chemotherapy before or after surgery. Only 677 patients (19.2%) received it. Younger age, insurance, higher neighborhood income and treatment at an academic or research program predicted receiving it. Median survival was 24.7 months (22.4 to 26.1) with guideline therapy versus 13.7 months (13.2 to 14.4) without, and 5-year survival was 17.7% (14.7 to 21.3%) versus 8.0% (7.0 to 9.3%). In adjusted analysis, the hazard ratio for death with guideline therapy was 0.66 (95% confidence interval 0.59 to 0.74). A propensity-matched comparison gave similar results. Among guideline-treated patients, survival did not differ significantly between chemotherapy before surgery (304 patients) and after (373). The authors concluded that guideline therapy is associated with better survival but used in a minority of patients. They noted that guideline-treated patients were generally younger and healthier, so selection bias may explain part of the difference.

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 database (cohort comparison of treatment groups, with multivariable and propensity-matched analyses)
• Who was studied: 3,534 patients in the US National Cancer Database with stage I–III epithelioid malignant pleural mesothelioma (pleura as primary site, known laterality and treatment, with follow-up), diagnosed 2004 to 2016
• Exposure: Not asbestos. The study looked at treatment: guideline-concordant therapy, defined as cancer-directed surgery plus induction or adjuvant chemotherapy, compared with all other treatment or no treatment. It also looked at the timing of chemotherapy relative to surgery.
• Main results:
  • Of 3,534 patients, 677 (19.2%) received guideline-concordant therapy and 2,857 (80.8%) did not
  • In multivariable analysis, younger age, being insured, higher census-tract income and treatment at an academic or research program predicted receiving guideline-concordant therapy
  • In the whole cohort, median survival was 24.7 (22.4–26.1) months with guideline therapy versus 13.7 (13.2–14.4) months without. Five-year survival was 17.7% (14.7–21.3%) versus 8.0% (7.0–9.3%), P less than 0.001.
  • In the adjusted Cox model, NCCN guideline therapy had a hazard ratio for death of 0.66 (95% confidence interval 0.59–0.74), P less than 0.001
  • In the propensity-matched groups, median survival was 24.7 (22.4–26.1) months with guideline therapy versus 15.6 (14.5–17.4) months without. Five-year survival was 17.7% (14.7–21.3%) versus 10.7% (8.3–13.8%), P less than 0.001.
  • Among guideline-treated patients, survival did not differ significantly between induction chemotherapy (304 patients) and adjuvant chemotherapy (373 patients). Median survival was 24.9 versus 24.5 months and 5-year survival 14.9% versus 20.1%, P=0.444.
  • Among patients who had surgery, 30-day mortality was 22 (9.5%) of 231 in the non-guideline group versus 12 (1.8%) of 677 in the guideline group, P less than 0.001
• The authors' conclusion: The authors concluded that most patients with potentially resectable epithelioid mesothelioma are not managed according to national guidelines. They also concluded that those who receive guideline-concordant therapy have significantly better short- and long-term outcomes, and that chemotherapy timing (before or after surgery) had no significant impact on overall survival.
• Limitations the authors state:
  • Possible selection bias: guideline-treated patients were generally younger and healthier, which could account for better survival
  • Factors such as pulmonary function, functional status, smoking history and specific co-morbidities could not be controlled for
  • The exact surgical procedure (for example extrapleural pneumonectomy versus pleurectomy/decortication) and the extent of resection could not be determined from database coding
  • The reason for not giving induction chemotherapy could not be determined
  • The analysis could not tell whether patients completed all planned chemotherapy
  • No information on disease recurrence or its treatment

Topics

Medical terms in this study, explained in our Lexicon: Epithelioid, Mesothelioma, Multimodal Therapy, Chemotherapy, Pleural Mesothelioma, Median Overall Survival, Overall Survival.

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• Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival — I.A. Elliott, H. He, et al. (2023)
• A Real-World Analysis of the Use of Systemic Therapy in Malignant Pleural Mesothelioma and the Differential Impacts on Overall Survival by Practice Pattern — K. Kerrigan, Y. Jo, et al. (2022)
• Multimodal therapy of epithelioid pleural mesothelioma: improved survival by changing the surgical treatment approach — L.V. Klotz, H. Hoffmann, et al. (2022)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)

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