Background
Phase II trial (CALGB 8984). 59 patients with T1 or T2 rectal adenocarcinoma within 10 cm of the anal verge, clinically N0. Received preoperative 5-FU continuous infusion for 3 days + CRT (45 Gy), then local excision (transanal resection). Exploratory analysis of sphincter preservation and recurrence in favorable low rectal cancer.
Interventions and follow up
Arm A: 5-FU 300 mg/m²/day CI + RT 45 Gy/25 fx → transanal local excision 4–6 weeks post-RT → additional 5-FU × 2 cycles postoperatively
Primary endpoint: Sphincter preservation and local recurrence
mFollow up: 60 month
Primary endpoint: Sphincter preservation and local recurrence
mFollow up: 60 month
Results
pCR: 44% (T2), 40% (T1)
5-yr OS: 85% (T1), 65% (T2)
Local recurrence (T2): 18%
Sphincter preservation: 100% (all patients — primary intent)
5-yr OS: 85% (T1), 65% (T2)
Local recurrence (T2): 18%
Sphincter preservation: 100% (all patients — primary intent)
Adverse events
Main adverse events: Grade ≥3 acute GI toxicity ~30%. Wound healing complications in 13%. Anastomotic dehiscence not applicable (local excision). Acceptable toxicity profile.
Conclusions
Preoperative CRT followed by local excision (sphincter-sparing) achieves 100% sphincter preservation in T1-T2 low rectal cancer. pCR rates of ~40–44% are achievable. Local recurrence rates of ~18% in T2 lesions are acceptable in patients unwilling or unable to undergo APR. This established the concept of downstaging prior to local excision for organ preservation.
Key Limitations
Key Limitations: Small phase 2 study — not powered for efficacy. T2 local recurrence of 18% is significantly higher than APR (standard of care). This approach is not appropriate for standard surgical candidates; reserved for patients refusing APR or with medical comorbidities. Subsequent ACOSOG Z6041 with intensified regimen also showed high local recurrence in T2 lesions (21.7%), suggesting local excision after CRT for T2 remains suboptimal unless pCR is achieved.
Clinical Context
CALGB 8984 established the investigational framework for organ-preserving surgery (local excision after CRT) in low rectal cancer. The watch-and-wait paradigm (Habr-Gama, Renehan, IWWD) represents the next step: avoiding surgery entirely in clinical complete responders. Local excision after CRT is now considered a reasonable option for carefully selected T2 patients (clinical CR or near-CR) who decline radical surgery.
References