Causes of Death After Surgery Among Cancer Patients: A Population-based Cohort Study

Abstract

Introduction: Recent advancements in surgical techniques and perioperative care have improved cancer survival rates, yet postoperative comorbidity and mortality remain a critical concern. Despite progress in cancer control, systematic analyses of long-term mortality trends and competing risks in surgery-intervened cancer populations are lacking. This study aimed to quantify temporal patterns of postoperative mortality causes across 21 solid cancers and identify dominant non-cancer risk factors to inform survivorship care strategies.

Methods: This retrospective, population-based cohort study analyzed data from 3,424,671 patients (including 2,371,058 surgical cases) diagnosed with 21 solid cancers between 1992 and 2021, sourced from the SEER database. Competing risk models were applied to assess cumulative mortality rates from index-cancer, non-index-cancer, and non-cancer causes, with stratification by cancer type. Surgical interventions were evaluated across short-term (30-day) and long-term follow-up periods, with primary outcomes focused on mortality attribution and secondary outcomes on temporal dominance shifts.

Results: In this population-based retrospective cohort study of 3,424,671 patients with 21 solid cancers (1992-2021), non-cancer deaths surpassed index-cancer mortality in 14 malignancies (e.g., prostate, breast, colorectal), accounting for 48.7% of post-surgical deaths, with cardiovascular diseases and infections as primary contributors. By the 2020s, non-cancer causes emerged as the leading mortality driver in these cancers. However, index-cancer mortality remained predominant in pancreatic, ovarian, and brain tumors, highlighting the persistent therapeutic gaps. Surgical resection significantly altered mortality profiles for cancer population, with a 95.7% increase in non-cancer mortality for lung cancer and an 87.3% increase for pancreatic cancer (P < 0.001), underscoring the critical need for enhanced postoperative comorbidity management. While 1-month post-surgical mortality improved over three decades for most solid cancers, disparities persisted in brain, biliary tract, and colorectal cancers. These findings advocate for multidisciplinary strategies prioritizing non-cancer comorbidities, particularly cardiovascular and infectious risks, to optimize long-term survival in cancer survivors.

Conclusion: This study highlights a paradigm shift in postoperative mortality, with no-cancer cause of deaths now surpassing cancer-related deaths in most solid tumors. These findings underscore the urgency of integrating multidisciplinary care targeting cardiovascular health and infection prevention into survivorship programs.