Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature.

BACKGROUND Neoadjuvant long-course chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. OBJECTIVE We report an evidence-based systematic review of published data supporting the optimal time to perform surgical resection after long-course neoadjuvant therapy. DATA SOURCES A systematic literature search was undertaken of the MEDLINE and Embase electronic databases from 1995 to 2012. STUDY SELECTION English language articles were included that compared outcomes following rectal cancer surgery performed at different times after a long course of neoadjuvant radiation-based therapy. INTERVENTIONS : Patients received a long course of neoadjuvant therapy followed by radical surgical resection after an interval period. MAIN OUTCOME MEASURES The rates of tumor response, R0 resection, sphincter preservation, surgical complications, and disease recurrence were the primary outcomes measured. RESULTS Fifteen studies were identified: 1 randomized controlled trial, 1 prospective nonrandomized interventional study, and 13 observational studies. Studies compared time intervals that varied between <5 days and >12 weeks, with a large degree of variation in what the standard interval length was considered to be. Four of the 7 studies that reported rates of pathological complete response identified significantly higher rates with an extended interval between chemoradiotherapy and surgery; 3 of 8 studies demonstrated increased primary tumor downstaging with a longer interval. No significant differences have been consistently demonstrated in rates of surgical complications, sphincter preservation, or long-term recurrence and survival. LIMITATIONS Neoadjuvant regimes, indications for neoadjuvant therapy, and time intervals after chemoradiotherapy were heterogeneous between studies; consequently, meta-analysis could not be performed. CONCLUSIONS There is limited evidence to support decisions regarding when to resect rectal cancer following chemoradiotherapy. There may be benefits in prolonging the interval between chemoradiotherapy and surgery beyond the 6 to 8 weeks that is commonly practiced. However, outcomes need to be studied further in robust randomized studies.