Background
Single-institution series (Wayne State, n=28) of localized anal squamous cell carcinoma treated with neoadjuvant concurrent chemoradiation, with surgery reserved for residual disease. Established the foundational sphincter-sparing paradigm in anal cancer.
Interventions and follow up
Radiotherapy: 30 Gy in 15 fractions via AP/PA fields to pelvis, medial inguinal nodes, and anal canal
Chemotherapy: 5-fluorouracil 1000 mg/m2/day ×4 days + mitomycin-C single 15 mg/m2 bolus, concurrent with RT
Surgery: abdominoperineal resection (APR), initially planned for all, later reserved as salvage
Primary endpoint: pathologic response and locoregional control; follow-up not formally reported
Chemotherapy: 5-fluorouracil 1000 mg/m2/day ×4 days + mitomycin-C single 15 mg/m2 bolus, concurrent with RT
Surgery: abdominoperineal resection (APR), initially planned for all, later reserved as salvage
Primary endpoint: pathologic response and locoregional control; follow-up not formally reported
Results
Clinical complete response: 86% (24/28 patients)
Pathologic complete response: 5/6 initial patients had no residual tumor in APR specimen, prompting a shift to salvage-only surgery
Sphincter preservation: achieved in the majority, avoiding routine APR
Pathologic complete response: 5/6 initial patients had no residual tumor in APR specimen, prompting a shift to salvage-only surgery
Sphincter preservation: achieved in the majority, avoiding routine APR
Adverse events
Dermatologic/GI: radiation dermatitis and diarrhea
Hematologic: myelosuppression from mitomycin-C and 5-FU; most events manageable and reversible after completion of therapy
Hematologic: myelosuppression from mitomycin-C and 5-FU; most events manageable and reversible after completion of therapy
Conclusions
Concurrent 5-FU/mitomycin-C chemoradiation produced high complete response rates in anal squamous cell carcinoma, leading the authors to conclude that routine abdominoperineal resection was unnecessary and could be reserved for salvage.
Key Limitations
Small, uncontrolled single-institution series with no comparator arm and no formal long-term survival follow-up. Radiation dose (30 Gy) was lower than later definitive regimens; findings were hypothesis-generating.
Clinical Context
The original Nigro regimen established definitive chemoradiation as organ-sparing primary therapy for anal cancer, superseding upfront APR. Later randomized trials (RTOG 98-11, ACT II) refined and confirmed 5-FU/mitomycin chemoradiation as the ASCO/ESMO-endorsed standard.