KEY POINTS
- NOM-3/TNT was a prospective single-center cohort evaluating an intentional watch-and-wait strategy in 24 patients with nonmetastatic rectal adenocarcinoma accessible to digital examination. Patients had selected small or intermediate-sized tumors; circular tumors or lesions >7 cm were excluded because of their low expected probability of sustained complete response.
- Treatment consisted of 25 Gy in five consecutive 5-Gy fractions using VMAT, followed one week later by consolidation FOLFOX4 every two weeks. Enlarged lateral pelvic nodes could receive a simultaneous integrated boost of 30 or 35 Gy in five fractions.
- The key de-escalation step was assessment after the first three FOLFOX4 cycles, around six weeks of chemotherapy. Patients with <50% tumor shrinkage by digital examination were classified as poor responders and sent directly to surgery; those responding continued to six cycles, while a complete responder could enter surveillance immediately. The 50% cutoff was arbitrarily chosen and had not been validated.
- At the midpoint assessment, chemotherapy was stopped in 6/24 patients (25%): one had already achieved a clinical complete response and five poor responders proceeded to TME. Grade 3–4 acute toxicity occurred in 17% of patients receiving six weeks versus 33% among those receiving the full 12 weeks, although groups were not randomized.
- After all response assessments, 8 patients (33%) had cCR and 8 (33%) near-cCR, so 16 entered watch-and-wait. Three near-complete responses subsequently converted to cCR, producing 11/24 patients (46%) who achieved cCR at some point.
- Regrowth was frequent. 7/16 patients (44%) entering surveillance developed regrowth, all within the first year; estimated two-year regrowth incidence was 46% (95% CI 21–71%). Regrowth occurred in only 1/8 initial cCR patients (13%) but in 6/8 near-cCR patients (75%), making persistent near-cCR a particularly concerning state.
- At two years, sustained cCR was 36% (95% CI 16–56%), overall survival 88%, organ-preservation-adapted disease-free survival 66%, and stoma-free survival 53%. Five patients (21%) developed distant metastases; none occurred among the nine patients with sustained cCR at last follow-up.
CLINICAL TAKEAWAY
Mid-treatment response assessment may spare some patients unnecessary chemotherapy and move obvious nonresponders to surgery earlier, but this study does not establish that the strategy improves oncologic safety. Most importantly, persistent near-cCR behaved very differently from true cCR, with 75% regrowth in this small cohort, suggesting that prolonged surveillance of near-complete responses after this TNT schedule deserves caution.