PhD defence L.J.X. (Louis) Giesen

Brief summary on the aim of the doctoral thesis:

Colorectal cancer (colorectal carcinoma) is a common disease in the Western world. In 2021, about 13000 patients were diagnosed with colorectal carcinoma in the Netherlands. In about 1 in 3 patients, the tumour is located in the last part of the colon (the rectum). Partly because of the differences in treatment, prognosis and tumour biology, colon and rectal carcinoma are generally considered two different entities. (1) Treatment of primary rectal carcinoma usually involves surgery to remove the rectum and surrounding fatty tissue with associated lymph nodes (TME surgery, total mesorectal excision). (2) Depending on the tumour stage, patients are sometimes pre-treated with radiotherapy (radiation) or chemoradiation (radiation combined with chemotherapy). In the Netherlands, this operation is mostly performed with keyhole surgery (laparoscopy) and nowadays increasingly with the help of a robot. The latter seems to be a safe way, but it is not yet clear whether it also offers gains for the patient compared to standard laparoscopy. (3) Potential advantages of the robot include the three-dimensional image that allows even better imaging of critical structures such as nerves, and the instruments that can articulate and therefore work accurately in a small space (such as the small pelvis in rectal surgery). Despite these surgical techniques, there is still a significant risk of developing (serious) complications and about 1 in 5 patients will end up with a permanent stoma after rectal surgery. In addition, rectal surgery is associated with a substantial deterioration in quality of life. This is caused, among other things, by bowel dysfunction, incontinence and sexual dysfunction that frequently occur after this surgery. (4) In recent years, several studies have shown that rectal resection can be omitted in some cases. In patients with an early form of rectal carcinoma, local removal, or local excision (LE), is a proven safe treatment. This rectal-sparing treatment has the advantage of preserving anorectal function and providing far fewer complications and a better quality of life compared with TME surgery. It is being investigated whether there is an oncologically safe option for rectal sparing treatment also in patients with rectal carcinoma not eligible for local excision. The STARTREC study is looking at whether these patients can first undergo radiotherapy or chemoradiation followed by local excision, or in the case of a complete response, a wait-and-see policy. (5) In addition, the TESAR study is investigating the possibility of local excision followed by radiotherapy, in both cases compared with TME surgery. (6) In patients with locally advanced-stage rectal carcinoma undergoing neoadjuvant chemoradiation, it appears that in about 20% of cases there is no tumour remnant. Here, it is also possible to opt for a wait-and-see policy, in which the patient is closely monitored (watchful waiting). In about 25% of cases, a recurrence will occur that will still require surgical treatment. (7) These aforementioned developments mean that treatment of rectal carcinoma is becoming increasingly 'tailor-made' on the basis of tumour and patient characteristics. These developments are supported by multiple randomised studies. Although randomised studies minimise the risk of confounding, their external validity is reduced. Older and high-risk patients are often inadequately represented in clinical trials. Here, population-based cohort studies come in handy because real-world data can be used to obtain a better reflection of daily clinical practice. Furthermore, they can also be used to analyse differences between hospitals, the application of new treatment techniques and guidelines. The aim of this thesis is to gain insight into and evaluate the impact of several recent developments on the (surgical) outcomes and treatment of rectal carcinoma in the Netherlands.