Squamous cell carcinoma antigen: a potentially useful prognostic marker in squamous cell carcinoma of the anal canal and margin.

BACKGROUND: The objective of this retrospective study was to investigate the predictive value of pretreatment serum squamous cell carcinoma antigen (SCCAg) levels in 174 patients with squamous cell carcinoma of the anus who received concurrent chemoradiation between 1997 and 2010. METHODS: Pretreatment serum SCCAg measurements in patients with histologically diagnosed squamous cell carcinoma of the anal canal and margin who received chemoradiation were compared with clinical tumor classification and lymph node status for prognostic/predictive ability, including 1) tumor response after the completion of chemoradiation treatment, 2) disease recurrence, and 3) overall survival. Clinical measurements and scores were compared using Spearman rank tests, and survival was assessed in both univariate and multivariate survival analyses. RESULTS: The median pretreatment levels of SCCAg according to clinical tumor classification and clinical lymph node status were 0.8 µg/L in T1 tumors, 1.90 µg/L in T2 tumors, 2.5 µg/L in T3 tumors, 3.8 µg/L in T4 tumors, 1.35 µg/L in patients with N0 status, and 3.05 µg/L in patients with N0+ status (correlation coefficient: T-classification, 0.43; lymph node status, 0.38; both P < .00001). Of the patients who had normal SCCAg levels, 95% achieved a complete response after initial treatment; and, of those who had elevated SCCAg levels, 86% achieved a complete response (P = .05). Overall survival (hazard ratio, 2.5; P = .007) and disease-free survival (hazard ratio, 2.2; P = .058) were worse for those who had elevated pretreatment serum SCCAg concentrations. CONCLUSIONS: Pretreatment SCCAg levels in patients with squamous cell carcinoma of the anal canal and margin were correlated with clinical tumor classification and clinical lymph node status. Elevated levels of SCCAg were associated with a reduced chance of achieving a complete response and an increased chance of recurrence and death. The authors recommend further studies to determine the prognostic value of SCCAg in anal squamous cell carcinoma and suggest the potential use of SCCAg as a stratification factor in future trials.

Anal cancer: is neoadjuvant cisplatin chemotherapy or chemoradiotherapy friend or foe?

This Practice Point commentary discusses the findings of the Intergroup RTOG 98-11 trial, which aimed to investigate both the potential role of cisplatin as neoadjuvant chemotherapy, and also its role concurrently in combination with radiotherapy, for anal-canal carcinoma. Although chemoradiotherapy has had an important effect on the treatment of anal cancer, and allows preservation of anorectal function with survival rates similar to or better than those of surgical treatment, overall survival rates for advanced tumors are still in the region of 50-60% at 5 years. A strong theoretical rationale for cisplatin-based treatment in anal cancer exists; several phase II trials have demonstrated a high response rate with reduced colostomy rates. The Intergroup results are disappointing in that neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, followed by cisplatin-based chemoradiotherapy did not improve overall survival, disease-free survival and locoregional control when compared with the standard treatment of combined 5-fluorouracil and mitomycin chemoradiotherapy.

Can histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival?

PURPOSE: This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6-12 weeks later by surgical excision. The CRM rate and incidence, site, and pattern of local and systemic recurrences were recorded. The median follow-up was 25 months. RESULTS: The overall median survival was 37 months, with a 5-year overall survival rate of 34%. Of the 150 patients, 122 underwent curative resection; 12% had a complete pathologic response, and downstaging to pT1-T2 occurred in an additional 16%. A negative CRM (R0) was achieved in 65% overall (98 of 150). Local recurrence occurred in 10% of those with R0 resection and 62% of those with R1-R2 resections. Distant metastases occurred in 29% of those with R0 resections and 75% of those with R1-R2 resections. The 3-year disease-free and 3-year overall survival rate was 9% and 25% and 52% and 64%, respectively, for patients with and without a histologically positive CRM. CONCLUSION: After 5-fluorouracil-based CRT, a positive CRM predicted for a high risk of subsequent local recurrence and a 3-year disease-free survival rate of only 9%. For this reason, the CRM should be considered a major prognostic factor and should be validated in future trials as an early alternative clinical endpoint.