Junting Guan, Jiyuan Chen, Shengqi Pan, Qi Li, Guiyu Wang, Qingchao Tang
LRRC is not merely residual disease but an evolutionarily progressed tumor entity characterized by persistence and dominance of truncal drivers with acquisition of clinically relevant alterations. Profiling recurrent lesions may guide therapy as primary tumor profiling alone may miss potentially actionable alterations present in recurrent lesions.
BACKGROUND: Synchronous multiple primary colorectal cancer (SMPCRC) is rare and often shows molecular heterogeneity between primary lesions. Treatment decisions are particularly challenging in complex scenarios involving multiple independent lesions, distant metastasis, and advanced age with intolerance to standard chemotherapy.
CASE PRESENTATION: A 77-year-old man presented with hematochezia and was diagnosed with four independent neoplastic lesions within three months: a primary rectal lesion (pT3N1aM0), a sigmoid colon primary carcinoma, a proximal rectal adenoma with focal intramucosal carcinoma, and an adenocarcinoma of the transverse colon near the splenic flexure [resected by endoscopic submucosal dissection (ESD) three months later]. Bilateral hepatic metastases were detected six months postoperatively, with the carcinoembryonic antigen (CEA) level still within the reference range at diagnosis. Molecular testing of the two primary carcinomas revealed marked discordance: the primary rectal lesion carried mutation signals in both KRAS exon 4 and NRAS exon 2, whereas the sigmoid colon lesion was entirely RAS/RAF/PIK3CA wild-type - testing either lesion alone would have led to opposite anti-EGFR treatment decisions. Given the patient's advanced age and intolerance to standard chemotherapy, a staged, multimodal integrated strategy was adopted: synchronous surgery for three primary lesions, minimally invasive ESD of the transverse colon lesion, artificial ascites-assisted percutaneous microwave ablation (AA-MWA) for liver metastases, and individualized adjustment of chemotherapy (switched from CAPEOX to oxaliplatin plus raltitrexed because of intolerance). Over 18 months of follow-up, no radiological recurrence was observed and the patient remained in good general condition.
CONCLUSIONS: This case demonstrates that primary lesions in SMPCRC can harbor substantial molecular heterogeneity, such that single-lesion testing may be insufficient to guide treatment decisions in complex scenarios. For elderly patients intolerant to standard regimens, a staged, multimodal integrated approach (synchronous surgery + ESD + AA-MWA + individualized chemotherapy adjustment) may serve as a feasible comprehensive treatment option.