Postoperative Complications Independently Predict Cancer-Related Survival in Peritoneal Malignancies

Our plain-English summary of Postoperative Complications Independently Predict Cancer-Related Survival in Peritoneal Malignancies, by M.H.A. Choudry, Y. Shuai, H.L. Jones, et al (Annals of Surgical Oncology, 2018).

The study

• Authors: M.H.A. Choudry, Y. Shuai, H.L. Jones, R.K. Pai, J.F. Pingpank, S.S. Ahrendt, M.P. Holtzman, H.J. Zeh, D.L. Bartlett
• Journal: Annals of Surgical Oncology
• Published: 2018;25(13):3950-3959
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The authors hypothesized that postoperative complications after cytoreductive surgery-hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC) have a negative impact on perioperative and oncologic outcomes and that the novel Comprehensive Comorbidity Index (CCI) would be a better predictor of such outcomes than the traditional Clavien-Dindo classification (CDC).

Methods: The study used a prospective database of 1296 patients with peritoneal metastases (PM) undergoing CRS-HIPEC between 2001 and 2016. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with perioperative and oncologic outcomes. The Akaike information criterion and the Schwarz (Bayesian information) criterion were used to compare model fitting for CCI versus CDC.

Results: In this study, CRS-HIPEC was performed for malignant mesothelioma (12%) and PM from appendix (50%), colorectal (30%), and ovarian (8%) cancers. Major postoperative in-hospital complications (CDC grades 3-4) occurred for 24% of the patients. However, a range of CCI scores was calculated for each CDC grade because 36% of the patients experienced multiple complications. After a median follow-up period of 55 months, the median progression-free survival was 15 months, and the median overall survival was 39 months. In the multivariate Cox proportional hazards models, postoperative in-hospital complications (measured by CDC or CCI) were independent prognostic factors for 30-day post-discharge morbidity and readmission, as well as for survival. The CCI scores demonstrated higher prognostic sensitivity for these outcomes than CDC grades.

Conclusions: Reduction of postoperative complications after CRS-HIPEC is essential for optimal short- and long-term outcomes. For assessing total burden of postoperative complications per patient, CCI is superior to CDC and more sensitive for assessing surgery- and cancer-related outcomes after CRS-HIPEC.

In plain English

From a prospective database, the authors reviewed 1296 University of Pittsburgh patients treated with surgery plus heated abdominal chemotherapy (CRS–HIPEC) for cancer in the abdominal lining. Of these, 157 (12%) had malignant peritoneal mesothelioma, which starts in that lining; the rest had appendix, colorectal or ovarian cancer spread there. Asbestos is not discussed. Major in-hospital complications affected 308 patients (24%); 459 (36%) had more than one complication. Median overall survival was 39.3 months (95% CI 33.6–44.9) for all patients and 37.8 months (95% CI 24.6–50.9) for mesothelioma patients. In adjusted models, compared with no complication, overall survival was worse with grades 1–2 (hazard ratio 1.39, 95% CI 1.13–1.72) and 3–4 (hazard ratio 1.61, 95% CI 1.29–2.02) complications. Mesothelioma patients had higher odds of major complications than appendix cancer patients (odds ratio 1.9, 95% CI 1.22–2.89). The authors concluded that reducing complications is essential for short- and long-term outcomes. They judged a score summing all of a patient's complications (CCI) more sensitive than grading only the worst one (CDC). They noted a relatively small sample, a mixed patient group and retrospective bias.

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 review of a prospectively maintained single-institution database (surgical cohort)
• Who was studied: 1296 patients who had an initial CRS–HIPEC at the University of Pittsburgh, March 2001 to May 2017: appendix cancer 643 (50%), colorectal cancer 389 (30%), malignant peritoneal mesothelioma 157 (12%), ovarian cancer 107 (8%)
• Exposure: Not an asbestos exposure study. The factor studied was postoperative in-hospital complications after CRS–HIPEC. These were measured by the Clavien–Dindo classification (CDC) and by a cumulative score the article calls the Comprehensive Comorbidity Index (CCI).
• Main results:
  • Major in-hospital complications occurred in 308 of 1296 patients (24%); 459 patients (36%) had more than one complication
  • All patients: median overall survival after CRS–HIPEC was 39.3 months (95% CI 33.6–44.9), with 52% alive at 3 years and 39% at 5 years
  • Mesothelioma patients: median overall survival after CRS–HIPEC was 37.8 months (95% CI 24.6–50.9). Median progression-free survival was 13.7 months (95% CI 9.4–18.1).
  • Overall survival model across all patients, compared with no complication: hazard ratio 1.39 (95% CI 1.13–1.72) for CDC grades 1–2 and 1.61 (95% CI 1.29–2.02) for CDC grades 3–4. Using CCI instead, the hazard ratio was 1.01 (95% CI 1.01–1.02) per unit increase.
  • Progression-free survival model, compared with no complication: hazard ratio 1.32 (95% CI 1.06–1.65) for CDC grades 3–4 and 1.11 (95% CI 0.91–1.36) for CDC grades 1–2
  • Compared with appendix cancer, mesothelioma was associated with higher odds of major in-hospital complications (odds ratio 1.9, 95% CI 1.22–2.89). It was also associated with lower odds of complete macroscopic (CC-0) resection (odds ratio 0.47, 95% CI 0.29–0.75).
  • In-hospital complications predicted morbidity within 30 days after discharge: odds ratio 13.04 (95% CI 5.81–29.27) for grade 4 compared with no complication
  • For progression-free and overall survival, models using CCI fitted better than models using CDC by AIC and SBC criteria
• The authors' conclusion: The authors concluded that early postoperative complications have a negative impact on short-term outcomes and long-term cancer-related survival. They concluded that reducing complications and selecting patients carefully are essential. They also concluded that CCI assessed the total burden of complications per patient more accurately than CDC.
• Limitations the authors state:
  • Relatively small sample size, a varied (heterogeneous) patient population, and bias from the retrospective nature of the data
  • 60- or 90-day morbidity and mortality data, which may be more representative, were not available in the database
  • National Cancer Institute Toxicity Criteria data on complications were not collected

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer, Mesothelioma, Ovarian cancer, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Malignant Mesothelioma, Progression-Free Survival, Median Overall Survival.

Related studies

• Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion in Adolescent and Young Adults with Peritoneal Metastases — M. Dhir, L. Ramalingam, et al. (2017)
• Repeat Cytoreductive Surgery and HIPEC for Peritoneal Surface Malignancy and Peritoneal Carcinomatosis — J.F. Wong, G.H. Tan, et al. (2015)
• Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases — L.S. Kyang, N.A. Alzahrani, et al. (2019)
• Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy — B. Singh, G. Singh, et al. (2018)
• Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Asian patients: 100 consecutive patients in a single institution — M.C. Teo, G.H. Tan, et al. (2013)
• The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy — B. Moran, T. Cecil, et al. (2015)

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