Sur®ng prognostic factors in head and neck cancer at the Millennium F. Chiesa a,d, *, S. Mauri a,e , N. Tradati a , L. Calabrese a , G. Giugliano a , M. Ansarin a , J. Andrle a,f , S. Zurrida b , R. Orecchia c , C. Scully a,d a Head and Neck Division, European Institute of Oncology, Milan, Italy b Scienti®c Director's Oce, European Institute of Oncology, Milan, Italy c Radiotherapy Division, European Institute of Oncology and University of Milan, School of Medicine, Milan, Italy d Eastman Dental Institute, University College, London, UK e ENT Clinic, School of Medicine, University of Pavia, Italy f Department of Otorhinolaryngology and Head and Neck Surgery, 1st Medical Faculty of Charles University, Prague, Czech Republic Received 10 May 1999; accepted 17 May 1999 Abstract The ability to reliably predict cancer outcome could tailor therapy to the aggressiveness of the tumour to achieve the best results in terms of loco-regional control, overall survival and quality of life. Retrospective and prospective clinical trials involving large series of patients have validated some predictive clinical and pathological factors, whereas the utility of many other prognostic factors has not been established. This has led to some confusion in clinical practice. In order to clarify the signi®cance, role and cost of these prognostic factors we carried out a Medline search of all papers published between 1993 and 1998 concerning the reliability and cost of markers with prognostic signi®cance, in head and neck squamous cell carcinoma, and assessed the results according to a number of criteria relating to reliability and cost. Regarding reliability we classi®ed prognostic factors into: (1) those with a proven signi®cance based on the fact that they were unanimously reported as having an independent statistical correlation with outcome and prognosis; and (2) those for which results were not unanimous, and which signi®cance is still controversial. Cost analysis showed a substantial dierence between validated tests which are of low cost and experimental tests which are expensive. Based on these data regarding both the reliability and cost of each prognostic factor, we propose guidelines for their use in clinical practice in the year 2000. # 1999 Elsevier Science Ltd. All rights reserved. Keywords: Head and neck cancer; Prognostic factors; Biomarkers; Cost analysis; Reliability; Clinical practice 1. Introduction The ability to reliably predict cancer outcome is highly desirable. On the basis of such information, therapy could possibly be tailored to the aggressiveness of the tumour to achieve the best results in terms of loco-regional control, overall survival and quality of life. The considerable world-wide interest in this area of head and neck cancer is shown by the fact that, over the past 5 years, almost 2000 papers on prognostic factors have been published. Retrospective and prospective clinical trials involving large series of patients have validated some of these factors whereas, unfortunately, the utility of many others has not been established. Furthermore, most of the new pathological, biological and molecular markers have not been suciently tested on adequate numbers of patients. This has led to confusion in clinical practice. Another aspect leading to confusion is the indis- criminate use of terms such as prognostic factor, risk factor, marker, etc., in the literature; some authors using these terms more or less synonymously, others with more speci®c meanings. Furthermore, it has been the authors' experience from many centres that clinical records do not always record all the information derived from such investigation, even those which may be considered of established value. Inappropriate use of these data in planning treatment, far from improving patient care may indeed at the very least increase costs and even worsen prognosis. Thus, there is a need to clarify the reliability and signi®cance, 1368-8375/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S1368-8375(99)00043-3 Oral Oncology 35 (1999) 590±596 www.elsevier.com/locate/oraloncology * Corresponding author. Tel.: +39-02-57489490; fax: +39-02- 57489491. E-mail address: fchiesa@ieo.it (F. Chiesa)