title: Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy.
abstract: OBJECTIVE
  To evaluate the prognostic value of the posttreatment TNM stage as a predictor of outcome in locally advanced rectal cancers treated with preoperative chemotherapy and radiotherapy.
  
  
  METHODS
  Between 1993 and 2000, 128 patients with tethered (103) or fixed (25) rectal cancers were treated with 50 Gy preoperative pelvic radiotherapy and two cycles of concurrent 5-fluorouracil infusion (20 mg/kg/d) and leucovorin (200 mg/m(2)/d) chemotherapy on Days 1-4 and 22-25 and a single bolus mitomycin C injection (8 mg/m(2)) on Day 1. Of the 128 patients, 111 had Stage T3 and 17 Stage T4 according to the rectal ultrasound or CT findings and clinical evaluation. All 128 patients underwent surgery 8 weeks after chemoradiotherapy. Postoperatively, the disease stage was determined according to the surgical and pathologic findings using the American Joint Committee on Cancer TNM staging system.
  
  
  RESULTS
  Of the 128 patients, 32 had postchemoradiotherapy (pCR) Stage 0 (T0N0M0), 37 pCR Stage I, 26 pCR Stage II, 28 pCR Stage III, and 5 pCR Stage IV disease. Of the 128 patients, 79 had pCR Stage T0-T2, 35 pCR Stage T3, and 14 pCR Stage T4. The rate of T stage downstaging was 66% (84 of 128). Of the 128 patients, 25% achieved a pathologic complete response, and 31 (24%) had positive nodal disease. Lymphovascular or perineural invasion was found in 13 patients (10%). The 5-year disease-specific survival rate was 97% for pCR Stage 0, 88% for pCR Stage I, 74% for pCR Stage II, 44% for pCR Stage III, and 0% for pCR Stage IV (p = 0.0000059). The 5-year relapse-free survival rate was 97% for pCR Stage 0, 80% for pCR Stage I, 72% for pCR Stage II, 42% for pCR Stage III, and 0% for pCR Stage IV (p < 0.000001). In univariate analysis, the pretreatment tumor status (fixed vs. tethered tumors), the pCR TNM stage, T stage downstaging, pathologic T4 tumors, node-positive disease after chemoradiotherapy, and lymphovascular or perineural invasion were statistically significant prognosticators of disease-specific survival and relapse-free survival. pCR Stage T4 disease was a strong predictor of local recurrence. The 5-year local control rate was 98% for pCR T0-T2, 89% for pCR T3, and 65% for pCR T4 disease (p = 0.00044). In multivariate analysis, the pCR TNM stage was the most statistically significant independent predictor of survival (p = 0.003) and relapse-free survival (p < 0.001).
  
  
  CONCLUSIONS
  For patients who underwent preoperative chemoradiotherapy for locally advanced rectal cancer, the pCR TNM stage was a strong prognosticator of recurrence and survival. It can be used to identify high-risk patients for additional postoperative therapy.
authors.affiliation: Department of Radiation Oncology, Tom Baker Cancer Center, 1331 29th Street NW, Calgary, Alberta T2N 4N2, Canada. alexc@cancerboard.ab.ca
authors.forename: Alexander K P
authors.initials: AK
authors.lastname: Chan
authors.forename: Alfred
authors.initials: A
authors.lastname: Wong
authors.forename: Daryl
authors.initials: D
authors.lastname: Jenken
authors.forename: John
authors.initials: J
authors.lastname: Heine
authors.forename: Donald
authors.initials: D
authors.lastname: Buie
authors.forename: Douglas
authors.initials: D
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging / Q000379:methods*; D016017:Odds Ratio; D011379:Prognosis; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy; D012008:Recurrence; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D016685:Mitomycin; D002955:Leucovorin; D005472:Fluorouracil