KEY POINTS
- The prospective longitudinal cohort initially included 172 non-metastatic pMMR/MSS rectal cancer patients treated from 2021–2024 with immunotherapy-based total neoadjuvant therapy. After excluding patients with progression or death, 142 were analyzed for quality of life and 137 for anorectal function.
- The iTNT regimen used 25 Gy in five fractions, followed by 4–6 cycles of CAPOX plus a PD-1 inhibitor. Patients with a clinical complete response could enter watch-and-wait; others underwent local excision or total mesorectal excision.
- Among the QoL cohort, 57/142 patients (40.1%) achieved organ preservation, while 85 underwent TME. Complete response was substantially more common in the organ-preservation group (93.0% vs 30.6%), illustrating the major baseline and response-selection differences between the groups.
- Longitudinal EORTC assessments showed consistently better global health status, physical, emotional and social functioning with organ preservation. Treatment-by-time interactions were also significant for taste disturbance, stool frequency and embarrassment after correction for multiple comparisons.
- Anorectal recovery clearly diverged between strategies. LARS and Wexner scores improved progressively after organ preservation, whereas LARS remained largely unchanged and Wexner incontinence worsened over long-term follow-up after TME; both treatment-by-time interactions remained significant after false-discovery-rate correction.
- In multivariable analysis, undergoing TME was associated with 13.63-fold higher odds of major LARS (95% CI 3.69–50.33; P<.001). Each additional centimeter of tumor distance from the anal verge was protective, OR 0.67 (95% CI 0.53–0.81; P<.001).
- Median long-term follow-up for iTNT patient-reported outcomes was approximately 21 months. Exploratory comparison with a conventional TNT cohort suggested similar long-term function between treatment regimens among patients achieving organ preservation, while worse outcomes after iTNT were concentrated mainly among TME patients; different follow-up periods and regimens prevent causal comparison.
CLINICAL TAKEAWAY
The functional benefit of achieving organ preservation after iTNT appears substantial, especially for low rectal tumors: avoiding TME was associated with better long-term bowel function and quality of life. However, patients who achieved organ preservation had substantially more favorable disease and response characteristics, so the study supports the value of successful OP rather than proving that OP itself causes all of the observed benefit.