Risk Factors of Tumour Recurrence and Reduced Survival in Rectal Cancer

Sammanfattning: In Sweden, 2000 patients are diagnosed with rectal cancer annually. In 1995, the Swedish Rectal Cancer Registry (SRCR) was launched to supervise and assure the quality of the management of rectal cancer. Advances in the management of rectal cancer have reduced the local recurrence (LR) rate and improved survival. To improve the outcome further, identification of prognostic and predictive factors is important for optimal, personalised neoadjuvant/adjuvant treatment and follow-up strategies. This thesis identifies potential risk factors of tumour recurrence and reduced survival – i.e., surgery-related and tumour biology-related prognostic factors – in a cohort of patients registered in the SRCR between 1995 and 1997 with 5-year follow-up. SRCR data were used and for subgroups additional data from the original medical records were retrieved. In addition, SRCR data were validated. In Paper I, preoperative radiotherapy (RT) significantly reduced the LR rate irrespective of the tumour height. Moreover, preoperative RT and rectal washout reduced the LR rate after incidental perforation. Preoperative RT prolonged time to LR. LR was an isolated tumour manifestation in 39% of the patients with LR. Paper II showed that anastomotic leakage had no impact on the oncological outcome. In Paper III, incidental perforation was a significant risk factor of increased LR and overall recurrence rates as well as reduced overall and cancer-specific 5-year survival. In Paper I-III, the validity of SRCR data was acceptable. In Paper IV, high immunohistochemical expression of the tumour marker ezrin in primary tumours from patients with LR correlated to earlier occurrence of LR. A linkage of high ezrin expression and aggressive biological behaviour is suggested.