Aspects on local recurrence of rectal cancer

Rectal cancer is a common malignant disease in Sweden which is diagnosed in about 1,800 patients annually. Local failure, defined as residual or recurrent disease within the pelvis, is of major concern in rectal cancer treatment. Preoperative radiotherapy and refinements in surgery have increased local control and survival during the past two decades. Since extensive surgery and radiation have documented side effects, a more individualized therapy aiming at local control and cure with a minimized risk of morbidity is sought.

The aims of this thesis were to define localization, analyze possible causes, and explore potential prognostic factors for local failure in rectal cancer, ultimately aiming at improved local control in rectal cancer treatment with minimized morbidity.

The basis for the study was a consecutive population-based cohort of abdominally operated rectal cancer patients identified from the registry of the Regional Oncologic Center in Stockholm and registers in Norrköping and Uppsala. The patients were operated upon in centers that had adopted modern principles in rectal cancer surgery, including total mesorectal excision (TME) and were treated with preoperative radiotherapy as described in regional care programs. In the studies, revision and analysis of registered data, analyses of images of the recurrent tumor and histological analysis of the invasive front of the primary tumors were performed.

It is concluded that lateral lymph node metastases are not a major cause of local failure. Partial mesorectal excision may be associated with an increased risk of local recurrence of tumors in the upper rectum. Locally recurrent tumors are situated in the lower ¾ of the pelvis, suggesting that lowering of the upper limit of the radiation could be introduced. The anal sphincter complex with surrounding tissue can be excluded from the target volume in patients with primary tumors more than 5 cm from the anal verge. It is also concluded that tumor-specific factors such as distal tumor location, advanced T and N stage, and treatment-specific factors such as omission of radiotherapy, residual disease, and treatment at a center with a lower caseload are independent risk factors for local failure. Analyses of the invasive front of the primary tumor revealed that tumor budding determined by antibody clone MNF-116 might serve as an additional predictive marker for local recurrence. Despite advances in rectal cancer management over the past decades, locally recurrent tumor growths develop in a number of patients.

This thesis provides some insights with respect to localization, clinicopathological risk factors, and biological tumor markers. Since locally recurrent rectal cancer is a condition that is often extremely difficult to treat and is so devastating for the patient, further research in this field is warranted.

List of scientific papers

I. Syk E, Torkzad MR, Blomqvist L, Ljungqvist O, Glimelius B (2006). Radiological findings do not support lateral residual tumour as a major cause of local recurrence of rectal cancer. Br J Surg. 93(1): 113-9
https://pubmed.ncbi.nlm.nih.gov/16372254

II. Syk E, Torkzad MR, Blomqvist L, Nilsson PJ, Glimelius B (2008). Local recurrence in rectal cancer: anatomic localization and effect on radiation target. Int J Radiat Oncol Biol Phys. 72(3): 658-64. Epub 2008 May 19
https://pubmed.ncbi.nlm.nih.gov/18495376

III. Syk E, Glimelius B, Nilsson PJ, (2009). Factors influencing local failure in rectal cancer: analysis of 2315 patients from a population-based cohort. [Submitted]

IV. Syk E, Lenander C, Nilsson PJ, Rubio C, Glimelius B (2009). Tumour budding correlates with local recurrence of rectal cancer. [Manuscript]