Organ preservation after neoadjuvant therapy for esophageal cancer has gained significant attention. While the CROSS trial established neoadjuvant chemoradiotherapy (nCRT) followed by surgery as standard care, approximately 30% of patients achieve pathological complete response (pCR), prompting exploration of active surveillance (AS). The landmark SANO phase Ⅲ trial (2025) demonstrated non-inferior 2-year overall survival (74% AS vs. 71% surgery), with 31% of patients avoiding surgery. Multimodal assessment (endoscopic deep biopsy+endoscopic ultrasound+PET-CT) reduced residual disease misdiagnosis to 10%. The Asian-led NEEDS trial is evaluating definitive chemoradiotherapy with salvage surgery. Although immunotherapy boosts pCR rates to 40%-55%, challenges persist, including 8%-12% false-negative cCR assessments, limited long-term data, and East-West histological disparities. The 2024 NCCN guidelines conditionally recommend AS (Category 2B, prioritized for squamous cell carcinoma), emphasizing centralized implementation. Future directions involve circulating tumor DNA and radiomics for risk stratification to advance precise organ-preserving strategies.
The evidence base, technical specifications and clinical implementation conditions of organ preservation strategies after neoadjuvant therapy for esophageal cancer were systematically reviewed, to provide an integrated framework for precise clinical decision-making. Based on the SANO randomized controlled trial and a series of diagnostic accuracy studies, the evolution of active surveillance (AS), the performance of multimodal evaluation techniques, and the outcomes of salvage treatment after recurrence were summarized. The SANO trial demonstrated that patients with rigorously selected clinical complete response (cCR) who received AS had a 2-year overall survival rate of 74%, which was non-inferior to the immediate surgery group (71%; absolute difference 0%, 95%CI –7% to 7%). Thirty-one percent of patients successfully avoided esophagectomy by the end of follow-up. However, the 2-year disease-free survival rate was significantly lower in the AS group than that in the surgery group (74% vs. 92%). The locoregional recurrence rate was 48%, the 30-day mortality rate after salvage esophagectomy following definitive chemoradiotherapy reached 11%, which was 3.7-fold higher than that of elective surgery (RR=3.67, 95%CI 2.89-4.66); whereas in the SANO study, the 30-day mortality rate of salvage surgery after neoadjuvant chemoradiotherapy with active surveillance for recurrence was 4%, showing no significant difference compared with the 5% observed in the immediate surgery group. The false-negative rate of cCR assessment was 13.5%-19.2%, with a negative predictive value of only 68.7%, indicating that approximately one in three patients judged as cCR actually had residual disease. Current evidence with immature long-term survival data does not support AS as a routine recommendation. This strategy should be strictly limited to high-volume esophageal cancer centers, patients with esophageal squamous cell carcinoma, highly consistent multimodal evaluations, and fully informed and highly compliant patients. Future studies are needed to optimize risk stratification using biomarkers such as circulating tumor DNA, and to balance quality-of-life benefits and oncological safety through adaptive therapeutic strategies.
Objective To explore the safety of local excision and watch and wait (W&W) strategy in patients with mid-low rectal cancer who achieved clinical complete response (cCR) or near-cCR after neoadjuvant chemoradiotherapy (nCRT). MethodsWe retrospectively reviewed patients with mid-low rectal cancer who achieved cCR or near-cCR after nCRT at Peking Union Medical College Hospital between July 2017 and July 2023 and divided them into two groups based on their treatment strategy: local excision group (n=30) and W&W group (n=37). The primary outcome was disease free survival (DFS), and the secondary outcomes were overall survival (OS), recurrence-free survival (RFS), and metastasis-free survival. ResultsBaseline characteristics (including age, gender, and so on) were balanced and comparable between the two groups (P>0.05). Postoperative pathology in the local excision group showed ypT0 in 16 cases (53.3%), ypT1 in 3 cases (10.00%), ypT2 in 10 cases (33.3%), and ypT3 in 1 case (3.3%). Among the 10 cases of cCR in the local excision group, 7 cases (70.0%) achieved a pathological complete response. Among the 20 cases of near-cCR in the local excision group, 9 cases (45.0%) achieved pathological complete response. The median follow-up time was 38 months (range, 2 to 74 months). In the W&W group, tumor regrowth occurred in 13 cases (35.1%), distant metastasis in 7 cases (18.9%), and cancer-related death in 4 cases (10.8%); in the local excision group, local recurrence occurred in 3 cases (10.0%), distant metastasis in 6 cases (20.0%), and cancer-related death in 3 cases (10.0%). The local recurrence/relapse rate was higher in the W&W group than that in the local excision group (χ2=5.758, P=0.016), while no significant differences were found in the distant metastasis rate (χ2=0.013, P=0.911) or mortality (χ2=0.012, P=1.000). The local excision group had superior DFS (HR=0.373, P=0.031) and RFS (HR=0.238, P=0.014) compared with the W&W group. However, no significant differences were found in OS (HR=0.780, P=0.745) or metastasis-free survival (HR=1.027, P=0.962). ConclusionsIn patients with mid-low rectal cancer who achieved cCR or near-cCR after nCRT, given the limited sample size and number of events in this study, local excision showed potential advantages in improving DFS and RFS, whereas OS, distant metastasis rate, and mortality were comparable between the two groups.