Colorectal Surgery

Tumor–stroma ratio refines ctDNA and pTN-based risk in stage III colon cancer

In 206 stage III colon cancer patients receiving adjuvant chemotherapy, postsurgery ctDNA positivity was the strongest predictor of recurrence. Three-year recurrence risk was substantially higher for ctDNA-positive than ctDNA-negative patients, with a reported hazard ratio of 6.1. Stroma-high tumors independently carried recurrence risk comparable to pT4/pN2 disease in multivariable analyses. Among ctDNA-negative patients, combining pT stage, nodal status, and tumor–stroma ratio defined low-, intermediate-, and high-risk groups with widely separated three-year recurrence rates. Roughly one-third of patients lacked all high-risk features, suggesting potential for adjuvant de-escalation. Conversely, ctDNA-negative patients with pT4/N2 and stroma-high tumors may warrant treatment escalation despite undetectable ctDNA. 1

Organ-sparing after TNT in rectal cancer: watch-and-wait versus local excision

Total neoadjuvant therapy has increased clinical and pathological complete response rates in rectal cancer, expanding organ-preservation opportunities. Watch-and-wait after apparent complete response shows local regrowth rates around 20–30%, with worse distant metastasis-free and overall survival. These data underscore persistent uncertainty in defining true clinical complete response with current imaging and endoscopic tools. Local excision after TNT can confirm pathological response, remove residual resistant clones, and refine selection for durable organ preservation. The review highlights local excision as a diagnostic–therapeutic bridge between non-operative management and completion total mesorectal excision. 2

Late (5–10 year) recurrence in older colorectal cancer survivors is uncommon but stage-dependent

This SEER-Medicare cohort included 17,329 colon and 4,427 rectal cancer survivors aged 66 or older with stage I–III disease. All patients remained recurrence-free and without second primaries for at least five years post-diagnosis before analysis. Between years 5 and 10, late treated recurrence incidence was 4.4% for colon and 8.0% for rectal cancer survivors. More advanced initial stage predicted shorter time to late recurrence, with absolute differences between stage I and III most pronounced in rectal cancer among colorectal sites. Across cohorts, other-cause mortality exceeded cancer-specific mortality during years 5–10. These findings support tailoring extended surveillance intensity to initial stage while considering high competing non-cancer mortality in older survivors. 3

ASCEND-CRC: longitudinal profiling to intercept metastatic colorectal cancer resistance

ASCEND-CRC, within the ARPA-H ADAPT program, aims to synchronize metastatic colorectal cancer therapy with real-time tumor evolution. The trial uses repeated, multimodal profiling to capture transient adaptive states that precede overt clinical resistance. It moves beyond single pre-treatment biomarkers toward dynamic biomarker sets intended to directly guide treatment decisions over time. The program seeks to define scalable platforms for early detection of evolutionary escape routes and timely therapeutic redirection in metastatic colorectal cancer. 4