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Original Investigation
From the American Head and Neck Society
July 29, 2021

Association of Pharyngocutaneous Fistula With Cancer Outcomes in Patients After Laryngectomy: A Multicenter Collaborative Cohort Study

Author Affiliations
  • 1Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
  • 2Department of Otolaryngology–Head & Neck Surgery, University of Toronto, Toronto, Ontario, Canada
  • 3Department of Otolaryngology–Head & Neck Surgery, Washington University School of Medicine, St Louis, Missouri
  • 4Head & Neck Cancer Care, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • 5Department of Otolaryngology–Head & Neck Surgery, Mt Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  • 6Head & Neck Service, Memorial Sloan Kettering Cancer Center, New York, New York
  • 7Department of Head & Neck Surgery, Division of Surgery, MD Anderson Cancer Center, The University of Texas, Houston
  • 8Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
JAMA Otolaryngol Head Neck Surg. Published online July 29, 2021. doi:10.1001/jamaoto.2021.1545
Key Points

Question  Is the development of pharyngocutaneous fistula (PCF) after salvage laryngectomy associated with locoregional or distant control?

Findings  This multicenter collaborative cohort study of 550 patients found that the rate of distant metastatic disease was 13% higher in patients who developed PCF after salvage laryngectomy. Multivariable analysis, controlling for chemotherapy, lymphovascular invasion, extranodal extension, primary T category, and recurrence N category showed that PCF was independently associated with a 2-fold increase in distant metastases; however, no association was observed between PCF and locoregional control, overall survival, or disease-free survival.

Meaning  Pharyngocutaneous fistula, a common complication following salvage laryngectomy, is associated with an increased risk of developing distant metastases but not locoregional failure.

Abstract

Importance  Pharyngocutaneous fistula (PCF) results in an inflammatory reaction, but its association with the rate of locoregional and distant control, disease-free survival, and overall survival in laryngeal cancer remains uncertain.

Objective  To determine if pharyngocutaneous fistula after salvage laryngectomy is associated with locoregional and distant control, disease-free survival, and/or overall survival.

Design, Setting, and Participants  A multicenter collaborative retrospective cohort study conducted at 5 centers in Canada and the US of 550 patients who underwent salvage laryngectomy for recurrent laryngeal cancer from January 1, 2000, to December 31, 2014. The median follow-up time was 5.7 years (range, 0-18 years).

Main Outcomes and Measures  Outcomes examined included locoregional and distant control, disease-free survival, and overall survival. Fine and Gray competing risk regression and Cox-proportional hazard regression models were used for outcomes. Competing risks and the Kaplan-Meier methods were used to estimate outcomes at 3 years and 5 years.

Results  In all, 550 patients (mean [SD] age, 64 [10.4] years; men, 465 [85%]) met inclusion criteria. Pharyngocutaneous fistula occurred in 127 patients (23%). The difference in locoregional control between the group of patients with PCF (75%) and the non–PCF (72%) group was 3% (95% CI, −6% to 12%). The difference in overall survival between the group with PCF (44%) and the non–PCF group (52%) was 8% (95% CI, −2% to 20%). The difference in disease-free survival between PCF and non–PCF groups was 6% (95% CI, −4% to 16%). In the multivariable model, patients with PCF were at a 2-fold higher rate of distant metastases (hazard ratio, 2.00; 95% CI, 1.22 to 3.27). Distant control was reduced in those with PCF, a 13% (95% CI, 3% to 21%) difference in 5-year distant control.

Conclusions and Relevance  This multicenter retrospective cohort study found that development of PCF after salvage laryngectomy is associated with an increased risk for the development of distant metastases.

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