Prognostic factors for recurrence and survival in anal cancer: generating hypotheses from the mature outcomes of the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I)

Cancer. 2013 Feb 15;119(4):748-55. doi: 10.1002/cncr.27825. Epub 2012 Sep 25.


Background: Only 2 prospective studies have previously reported prognostic factors for anal cancer, European Organization for Research and Treatment of Cancer trial 22861 (EORTC 22861) and Radiation Therapy Oncology Group trial 98-11 (RTOG 98-11). Both of those trials reported that clinically positive lymph nodes and male sex predicted poorer overall survival (OS). The EORTC 22861 trial indicated that the same factors were prognostic for locoregional control. In the current report, the authors investigated potential prognostic factors from the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I), in which patients were randomized to receive either radiotherapy alone or chemoradiation (CRT) with concurrent 5-fluorouracil/mitomycin C.

Methods: In the ACT I trial, associations between several baseline characteristics and 3 endpoints were investigated: locoregional failure (LRF), anal cancer death (ACD), and OS. The analyses were restricted to 292 patients who received CRT, which subsequently became standard treatment. A score was derived using multivariable Cox regression to identify the set of factors that, together, had the best prognostic performance. This score was then validated with a large, independent prospective trial (the ACT II trial).

Results: Palpable, clinically positive lymph nodes were associated with LRF (P = .012), a greater risk of ACD (P = .031), and decreased OS (P = .006) in multivariable analyses. Men had worse outcomes than women for LRF (P = .036), ACD (P = .039), and OS (P = .008). On average, a lower hemoglobin level had an adverse effect on ACD (P = .008), and a higher white blood cell count had an adverse effect on OS (P = .001). However, external validation of the score was poor for LRF (area under the curve [AUC] = 54%) but was better for ACD (AUC = 67%) and OS (AUC = 63%).

Conclusions: The results from this analysis of the ACT I trial supported evidence for palpable lymph nodes and male sex as prognostic factors for LRF and OS, and lower hemoglobin levels and a higher white blood cell count were identified as prognostic factors for ACD and OS, respectively.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols
  • Anus Neoplasms / drug therapy*
  • Anus Neoplasms / mortality*
  • Anus Neoplasms / pathology
  • Anus Neoplasms / radiotherapy*
  • Chemoradiotherapy
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Hemoglobins / analysis
  • Humans
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage
  • Prognosis
  • Prospective Studies
  • Recurrence
  • Survival Rate
  • Treatment Outcome
  • United Kingdom


  • Hemoglobins
  • Mitomycin
  • Fluorouracil