Locally advanced rectal cancer : aspects on management, outcome and quality of life

Sammanfattning: Rectal cancer is common in Sweden, with about 1650 patients diagnosed annually. In 10-15% of the patients the tumour is locally advanced at diagnosis, i.e. the cancer is growing outside the mesorectal fascia, into adjacent organs in the pelvis. The incidence of local recurrences, after surgery for primary rectal cancer has decreased as a result of preoperative radiotherapy (RT) and improved surgical techniques, but still the local failure rate is 5-15%. Treatment of patients with locally advanced primary rectal cancer and recurrent rectal cancer remains a challenge but, with radical surgical resection 5-year survival rates up to 50-60% is reached at dedicated centres. The aim of this thesis was to analyse management, outcome and the quality of life in patients with both locally advanced primary rectal cancer and locally recurrent rectal cancer, focusing on the preoperative assessment and on multimodality treatment with a multidisciplinary approach. Two of the studies were population-based and included all patients in the Stockholm-Gotland region with respectively locally advanced primary rectal cancer and local recurrences during 1995-2005. The patients were identified by means of the colorectal cancer registry at the Regional Oncological Centre and their medical records were scrutinised. The other two studies involved patients with locally advanced rectal cancer at a single centre, the Karolinska University Hospital, and treated during 1991-2003. During 1995-2004 in the Stockholm region, 10% of all rectal cancer patients were found to have a locally advanced primary rectal cancer. In all patients with a potentially curative resection of primary rectal cancer treated during 1995-2003, a local recurrence of rectal cancer was detected in 6% by 2005. It was concluded that appropriate preoperative radiological tumour staging in patients with locally advanced rectal cancer increased both the proportion of patients who received neo-adjuvant treatment and the rate of potentially curative resections. Local control and survival were improved. Multidisciplinary team (MDT) discussions further enhanced the proportion of curative resections and local control, but no influence on survival was seen. The overall outcome for patients with locally recurrent rectal cancer was dismal, with a 5-year survival of 9%, but, in patients with a potentially curative resection, an improved estimated 5-year survival of 57% was obtained. A radical resection was necessary for cure and the proportion of curative resections had increased after improved preoperative management and refined surgery compared to an earlier study of local recurrences in Stockholm. After the introduction of a multimodality treatment programme for patients with rectal cancer, one third of the patients with locally advanced rectal cancer could be cured if a radical resection was performed. Patients with locally advanced primary rectal cancer had a higher rate of curative resections than patients with locally recurrent rectal cancer. The extensive surgery and RT led to a high morbidity. In measurements of the quality of life in disease-free patients treated for locally advanced rectal cancer several functions, such as role, social and physical function, were low compared with patients treated for primary resectable rectal cancer. This knowledge is valuable for counselling patients preoperatively and for giving adequate postoperative support. In conclusion, the management of patients with locally advanced rectal cancer can be further improved with adequate preoperative evaluation and staging and increased preoperative neoadjuvant radiochemotherapy followed by extensive surgery. The survival gain of additional adjuvant therapy remains to be studied. Multidisciplinary management of these patients is necessary.