Factors predicting recurrence in rectal cancer

Sammanfattning: Background: Rectal cancer treatment has improved through important incremental surgical and oncological developments over the past decades. Localized disease is highly treatable with multimodal surgical and oncological therapy. Prognosis is dependent on several factors with tumour stage at diagnosis being the most important. Furthermore, curative treatment is highly dependent on radical surgical resection. Positive circumferential resection margin (CRM), lateral lymph node metastases and tumour deposits are examples of high-risk clinical situations associated with increased risk of recurrence and subsequently impaired long-term outcome and are investigated in this thesis.Aims: Paper I & II, to investigate CRM-positive resections in rectal cancer and effect on local recurrence and distant metastasis risk. Paper III, to describe MRI-positive lateral lymph nodes – investigating therapy and outcome in high-risk rectal cancer. Paper IV, to investigate the prognostic significance of tumour deposits as a risk factor and in comparison with lymph node involvement in rectal cancer.Method: Paper I-II & IV are retrospective national cohort studies. Paper III is a retrospective regional cohort study. Patient data was gathered from the Swedish ColoRectal Cancer Registry, medical records and the Swedish Cause of Death registry. Patients for paper I & II were between 2005 – 2013, for paper III between 2009 – 2014 and för paper IV between 2011 – 2014.Main outcome measures: Paper I, local recurrence. Paper II, distant metastasis. Paper III, descriptive tumour characteristics, overall survival, local recurrence and distant metastasis. Paper IV, local recurrence, distant metastasis, overall and relative survival.Results and conclusions: Exact CRM was associated with increased local recurrence risk. Neoadjuvant radiotherapy does not decrease risk of local recurrence in CRM-positive patients. Only a subset of patients with R1-resection (CRM 0.0 mm) suffered local recurrence during follow-up. Exact CRM equal to or less than 1.0 mm may be a risk factor for distant metastasis. However, several other factors likely contribute to increased risk of distant metastasis in CRM-positive patients. MRI-positive lateral lymph nodes were associated with synchrounous distant metastasis. Neoadjuvant (chemo)radiotherapy, abdominal rectal resection and selective lymph node dissection may be a useful approach in patients with MRI-positive lateral lymph nodes. Tumour deposits increased risk of both local recurrence and distant metastasis and decreased survival. The prognosis of patients with tumour deposits were comparable to pN1a-b stage mesorectal lymph node involvement.