Long-term sequelae after cancer therapy—A necessary consequence of success?

Substantial progress in cancer survival was previously restricted to a few uncommon tumour types like Hodgkin’s lymphoma (HL), testicular carcinoma, and acute leukaemias in children. More recently, we have also seen improved long-term survival in several other tumours such as breast and colorectal cancer (1). These improvements are not as dramatic as those seen earlier, but as they affect much more frequent tumours they have a more substantial impact on not only population statistics but also resources. More effective treatments are the main reason for the dramatic improvements previously seen, but also explain a substantial part of the progress noted more recently in the more common types. More effective treatments have*/at least up to now*/meant both more, and more intensive, treatments. All surviving patients are thus at risk of suffering from late consequences caused by the treatments. This is of particular relevance when adjuvant treatments, or newer more intensive adjuvant treatments, are given to many patients though benefiting only a few of them. In this issue of Acta Oncologica, a review article is published on ‘Long-term sequelae after cancer therapy: survivorship after treatment for testicular cancer’, by Sophie Fosså. It is based on an Acta Oncologica lecture at the Oncologic Forum in Oslo in November 2002 (2). It gives a literature review and a description of the Norwegian experience. According to the Eurocare-3 study, age-standardized five-year survival in Norway is 96%, which in fact, numerically, is the very best among the regions/countries included in the study (3). Given the young age of patients with testicular cancer, as well as HL, and the high cure rates and intensive treatments, frequently involving both radiation therapy and chemotherapy, the knowledge about late sequelae from treatment in these tumour types is more extensive than that in other types. The most serious late toxicity of therapy is probably the development of a second malignancy. Unfortunately, other consequences are also highly relevant. Among those already recognized are late vascular events, various neurological problems, fatigue, and infertility. Psychological and cognitive problems have more recently been recognized in patients receiving adjuvant chemotherapy for breast cancer (4, 5). Precise knowledge of the mechanisms behind therapyinduced late sequelae, and how frequently they are seen, is important for a number of reasons. First of all, they may give clues as to how to modify treatments. Is it, for example, the radiation or a particular cytostatic drug that is of greatest importance, or do they interact synergistically? Although not known in all details, it is likely that chemotherapy substantially adds to the risk of solid second tumours (6). Second, follow-up routines and preventive measures, such as smoking cessation to prevent secondary lung cancer in HL survivors, may be intensified to decrease the risk to individual patients. Such routines are probably relevant for the patient’s remaining lifetime, and thus are resource demanding, particularly when affecting large patient groups. This is the case when new adjuvant treatments are given to breast and colorectal cancer patients, for example. The Nordic countries have unique possibilities to contribute to the knowledge base concerning the magnitude of risks, and also after long follow-up periods. There are many good examples of this, the presentation by S. Fosså being one of them (2). And yet, considering our opportunities, we have not fully taken up the possibilities and responsibilities. The national cancer registries are excellent sources to identify all cases, and, by linkage with other registries, many*/at least all severe events causing hospitalization*/ may be identified. However, the national registries do not contain sufficient information on stage and treatments. Many registries linked to regional, national, or Nordic clinical guidelines*/so-called care programmes*/frequently contain this information. A few of them also contain follow-up information. However, most of them suffer from many constraints, frequently due to lack of sufficient resources. These registries, which are of fundamental importance for quality control and of great relevance for research, must be an integrated part of the duties of healthcare systems. Politicians generally understand this, or at least they verbally express this to be the case, but resource allocation has not followed. Department heads and other responsible clinicians probably also understand their importance, but frequently do not give sufficient priority to allocating the necessary time. More user-friendly web-based systems will help, but the quality of many of these registries is still dependent on ‘scouting activities’ by enthusiasts. Banking of tissue materials is presently a prioritized activity for translational research activities, but EDITORIAL