Shintaro Hashimoto, Tetsuro Tominaga, Keisuke Noda, Toshio Shiraishi, Hiroki Katayama, Shoko Tei, Taiji Hida, Kazuki Motoyama, Shoto Yamazaki, Takashi Ohnoda, Hiroshi Maruta, Yuma Takamura, Rika Ono, Nobuhito Ogata, Makoto Hisanaga, Mitsutoshi Ishii, Masaaki Moriyama, Hidetoshi Fukuoka, Kazuo To, Kaido Oishi, Takashi Nonaka, Keitaro Matsumoto
CD ≥3 complications independently worsen RFS, OS, and CSS but do not significantly affect TTR after curative resection for pStage I-III CRC. IAI complications are particularly associated with worse cancer-specific mortality. This discordance suggests that severe complications may not primarily accelerate recurrence itself, but may instead impair survival after recurrence, highlighting possible mechanisms beyond direct recurrence acceleration.
BACKGROUND: Severe postoperative complications (Clavien-Dindo [CD] grade ≥ 3) may compromise long-term oncologic outcomes after colorectal cancer (CRC) surgery, but their impact across all pathological stages remains unclear.
METHODS: We retrospectively analyzed 1990 patients who underwent curative resection for pStage I-III CRC at six hospitals (2016-2021). Multivariable Cox proportional hazards models were used to evaluate recurrence-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), and time to recurrence (TTR). Stratified analyses were performed by pathological stage and complication type (intra-abdominal infectious complications [IAI] vs. non-IAI), and a 30-day landmark analysis was conducted.
RESULTS: CD ≥3 complications occurred in 128 patients (6.4%). On multivariable analysis, CD ≥3 complications were independent adverse prognostic factors for RFS (hazard ratio [HR] 1.84, P < .001), OS (HR 2.52, P < .001), and CSS (HR 2.04, P = .024), but not for TTR (HR 1.22, P = .451). Stage-stratified analyses showed significant associations with worse RFS and OS in pStage II-III, with trends in pStage I. CSS was significantly worse in pStage III (HR 3.06, P < .001). TTR showed no significant association with CD ≥3 complications in any pStage. IAI complications were independently associated with worse CSS (HR 2.21, P = .039), whereas non-IAI complications were not. These adverse effects persisted after 30-day landmark analysis.
CONCLUSIONS: CD ≥3 complications independently worsen RFS, OS, and CSS but do not significantly affect TTR after curative resection for pStage I-III CRC. IAI complications are particularly associated with worse cancer-specific mortality. This discordance suggests that severe complications may not primarily accelerate recurrence itself, but may instead impair survival after recurrence, highlighting possible mechanisms beyond direct recurrence acceleration.