Background
Phase II trial (ACOSOG Z6041). 77 patients with T2N0 distal rectal adenocarcinoma, within 8 cm from anal verge. Treated with intensified neoadjuvant CRT (capecitabine + oxaliplatin + RT) followed by local excision. Tested whether intensified neoadjuvant therapy could increase pCR rates enabling organ preservation in T2 tumors.
Interventions and follow up
Arm A: Capecitabine 825 mg/m² BID + oxaliplatin 50 mg/m²/wk + RT 54 Gy/30 fx → local transanal excision 6 weeks post-CRT
Primary endpoint: Composite 3-year survival without disease or salvage surgery
mFollow up: 56 month
Primary endpoint: Composite 3-year survival without disease or salvage surgery
mFollow up: 56 month
Results
pCR: 44.2%
3-yr survival without disease/salvage: 86.9% (T2), 97.8% if pCR
Local recurrence: 4 of 68 patients (5.9%) who underwent local excision
Salvage surgery rate: 7.4%
3-yr survival without disease/salvage: 86.9% (T2), 97.8% if pCR
Local recurrence: 4 of 68 patients (5.9%) who underwent local excision
Salvage surgery rate: 7.4%
Adverse events
Main adverse events: Grade ≥3 acute toxicity: 13.4% (diarrhea 3.9%, neuropathy 4.5%). Wound complications in 11.8%. No treatment-related deaths.
Conclusions
Intensified neoadjuvant CRT (capecitabine + oxaliplatin + 54 Gy) achieves a pCR rate of 44.2% in T2N0 distal rectal cancer. The composite endpoint was achieved in 86.9%, with low local recurrence (5.9%) after local excision. This demonstrates feasibility of organ-preserving surgery in selected T2 tumors with good neoadjuvant response.
Key Limitations
Key Limitations: Phase 2, single-arm study. Local excision was performed regardless of response — watch-and-wait not offered. Not directly comparable to standard radical surgery with TME. Local recurrence risk exists in non-pCR patients who underwent local excision (21% in ypT2 at 3 years). Oxaliplatin addition increased acute toxicity. Modern watch-and-wait approach avoids surgery entirely in cCR patients, which ACOSOG Z6041 did not test.
Clinical Context
ACOSOG Z6041 established intensified capecitabine + oxaliplatin + RT as a feasible neoadjuvant regimen for organ preservation in T2 rectal cancer. However, the watch-and-wait paradigm (IWWD) is now increasingly preferred for clinical complete responders. Local excision remains an option for partial responders when radical surgery is declined.
References