Immunotherapie-gebaseerde totale neoadjuvante therapie verbetert lymfeklierrespons en maakt lokale excisie mogelijk bij rectumcarcinoom

BACKGROUND: The immunotherapy-based total neoadjuvant therapy (iTNT) has improved response rates in locally advanced rectal cancer (LARC); however, a majority of patients do not achieve clinical complete response (cCR) and still require total mesorectal excision. High rates of ypT0-1 and particularly ypN0 in non-cCR patients suggest organ preservation via local excision (LE). This study aims to assess the feasibility of LE in LARC by comparing pathological lymph node responses after three neoadjuvant regimens. METHODS: We included 1568 LARC patients with pathological outcomes after neoadjuvant therapy in three cohorts: 238 received fluorouracil-based chemoradiotherapy (CRT); 1256 received total neoadjuvant therapy (TNT); and 74 received iTNT from the prospective TORCH trial (NCT04518280). Baseline characteristics among three cohorts were balanced using the stabilized inverse probability of treatment weighting (IPTW) method. RESULTS: After IPTW adjustment, the overall rates of positive lymph nodes after neoadjuvant therapy (ypN+) were 44.1%, 34.0%, and 13.4% in the CRT, TNT, and iTNT cohorts, respectively. Notably, pathologic complete response of lymph nodes was achieved in both ypT0 and ypT1 tumors following iTNT. In contrast, the ypN+ rates for ypT0 and ypT1 tumors remained high at 16.8% and 26.4% with CRT and 11.2% and 19.2% with TNT. Univariate regression analysis identified that ypT2-4, positive ypMRF, and positive ypEMVI were associated with higher ypN+ risk, rather than baseline clinical characteristics. CONCLUSIONS: iTNT markedly improved lymph node regression in ypT0-1 tumors compared to CRT or TNT. LE, guided by tumor response but not by baseline clinical stages, may be considered for organ preservation in near-cCR patients with LARC following iTNT.