Nodal stage is the key prognostic factor in synchronous and metachronous multiple primary colorectal adenocarcinoma after curative-intent resection: a retrospective study

Multiple primary colorectal cancer (MPCRC) is uncommon but clinically challenging, and differences between synchronous MPCRC (SMPCRC) and metachronous MPCRC (MMPCRC) remain incompletely defined. We compared clinicopathological and surgical features between SMPCRC and MMPCRC and explored prognostic factors for overall survival (OS) in MPCRC. This retrospective cohort study consecutively included patients with pathologically confirmed multiple primary colorectal adenocarcinoma who underwent curative-intent resection at our hospital. SMPCRC was defined as tumors identified within 6 months and MMPCRC as a subsequent primary diagnosed after 6 months. Clinicopathological and perioperative variables were extracted from medical records and pathology reports. Mismatch repair protein expression was assessed as an exploratory pathological variable. OS was analyzed using Kaplan–Meier methods and Cox proportional hazards regression. A total of 165 patients were included (120 SMPCRC and 45 MMPCRC) with follow-up until December 2024. Baseline characteristics were broadly comparable between groups. SMPCRC more frequently underwent laparoscopic surgery (97.5% vs 88.9%, p = 0.035) and had a higher lymph node yield (27.86 ± 13.32 vs 20.87 ± 14.07, p = 0.004). Vascular invasion was more common in SMPCRC (45.8% vs 26.7%, p = 0.026), and N-stage distribution differed between subtypes (p < 0.001). OS did not differ significantly between SMPCRC and MMPCRC. In multivariable analysis, N stage remained the only independent predictor of OS (HR 2.979, 95% CI 1.404–6.320, p = 0.004). Although SMPCRC and MMPCRC differed in several perioperative and pathological features, OS was primarily determined by N stage. N stage should be considered the key variable for prognostic stratification in resected MPCRC.