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Original Investigation
July 16, 2020

Adjuvant Systemic Chemotherapy vs Active Surveillance Following Up-front Resection of Isolated Synchronous Colorectal Peritoneal Metastases

Author Affiliations
  • 1Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands
  • 2Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands
  • 3Department of Medical Oncology, Catharina Cancer Institute, Eindhoven, the Netherlands
  • 4Department of Surgery, University Medical Centre Groningen, Groningen, the Netherlands
  • 5Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
  • 6Department of Public Health, Erasmus University Medical Centre, Rotterdam, the Netherlands
  • 7Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
  • 8GROW-School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands
JAMA Oncol. Published online July 16, 2020. doi:10.1001/jamaoncol.2020.2701
Key Points

Question  Is adjuvant systemic chemotherapy associated with improved overall survival compared with active surveillance in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases?

Findings  In this Dutch nationwide propensity score–matched cohort study including 393 patients, adjuvant systemic chemotherapy was associated with improved overall survival (median, 39 months) compared with active surveillance (median, 25 months). This difference in survival rates was statistically significant.

Meaning  In this study, adjuvant systemic chemotherapy was associated with improved overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases; however, randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association.

Abstract

Importance  To date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases.

Objective  To assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases.

Design, Setting, and Participants  In this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates.

Exposures  Adjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively.

Main Outcomes and Measures  Overall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity.

Results  Of 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P = .006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P = .02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95).

Conclusions and Relevance  Findings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.

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