On treatment and prognosis in epidermoid anal cancer

Epidermoid anal cancer is an uncommon, malignant disease that is diagnosed in approximately 100 patients annually in Sweden. The incidence is increasing worldwide. Over the past 30 years, a dramatic change in the therapeutic approach has occurred leading to non-surgical treatment with radiotherapy and chemotherapy being primary options. Inter-individual variation in treatment response exists and a proportion of patients require radical surgery for cure. Treatment regimens in current use yield good survival rates, but treatment related morbidity and the need for surgery still represent a problem. Reliable prognostic markers are lacking.

The aims of this thesis are to extend present knowledge on treatment, including surgery, and to explore different potential prognostic markers for the benefit of epidermoid anal cancer patients. The basis for this thesis was a consecutive, population-based cohort of 308 anal cancer patients from Stockholm-Gotland, collected 1985-2000. Therapeutic results were reviewed and prognostic markers explored.

It is concluded that results comparable to those in clinical trials are possible to achieve in an unselected, population-based series. Adherence to pre-determined treatment protocols, centralised management of patients within a multidisciplinary team and close follow-up may be key elements in the treatment of epidermoid anal cancer patients. In locally advanced cases, treatment results appear to be superior when neoadjuvant platinum-based chemotherapy is added to radiotherapy.

Assessment of treatment response after initial radiotherapy is of great importance, as further irradiation adds morbidity, but no survival benefits in poor responders. Salvage surgery can result in >50 per cent long-time survivors, but is associated with considerable post-operative morbidity. Clinicopathological parameters should be used for prognostic information with caution; however, stage appears to be of prognostic importance.

Archived tumour material was investigated, using immunohistochemistry, with respect to potential prognostic markers. Tumour budding appears to be of prognostic importance. Furthermore, Cyclin A expression, reflecting proliferation rate, may be a marker of radio sensitivity and a valuable prognostic marker in epidermoid anal cancer. Markers related to proliferation merit further investigation.

Future challenges include definition of optimal treatment regimens with regard to locally advanced tumours, but also smaller lesions. Access to prognostic and predictive markers may lead to a more individualised therapy.

List of scientific papers

I. Nilsson PJ, Svensson C, Goldman S, Ljungqvist O, Glimelius B (2005). Epidermoid anal cancer: a review of a population-based series of 308 consecutive patients treated according to prospective protocols. Int J Radiat Oncol Biol Phys. 61(1): 92-102.
https://doi.org/10.1016/j.ijrobp.2004.03.034

II. Nilsson PJ, Svensson C, Goldman S, Glimelius B (2002). Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg. 89(11): 1425-9.
https://doi.org/10.1046/j.1365-2168.2002.02231.x

III. Nilsson PJ, Rubio C, Lenander C, Auer G, Glimelius B (2005). Tumour budding detected by laminin-5 {gamma}2-chain immunohistochemistry is of prognostic value in epidermoid anal cancer. Ann Oncol. 16(6): 893-8.
https://doi.org/10.1093/annonc/mdi179

IV. Nilsson PJ, Lenander C, Rubio C, Auer G, Ljungqvist O, Glimelius B (2005). Prognostic significance of cyclin A in epidermoid anal cancer. [Submitted]