Familial Nasopharyngeal Carcinoma 6

138 R. Ove, R. R. Allison, and J. J. LuAnother confounding factor in analyzing resultsof historical series is that the results of modern seriesshow a substantial improvement in survival. This isquite likely due to improvements in imaging andadvances in radiotherapy technology (intensitymodulatedradiotherapy, IMRT), and increased dosewith techniques such as intracavitary brachytherapy.A substantial portion of this improvement is mostlikely due to stage migration, as more accurate stagingsecondary to improved imaging and the availabilityof positron emission tomography (PET) will tendto upstage patients formerly thought to be low risk.For carefully selected patients, radiotherapy alonecan offer excellent results. However, it is importantnot to neglect the benefits of multidisciplinary managementfor these patients, as for locally advancedcases. Attention to nutrition, swallowing function,dental issues, social support, and potential complicationsof therapy remain important. In addition, themultidisciplinary environment provides an appropriateforum for review of pathology in clinical context,and a mechanism for input from all appropriatespecialties regarding imaging and staging.10.2Evolution of StagingStaging of nasopharyngeal cancer, as with mostmalignancies, is a complex issue that evolves overtime as prognostic factors become apparent. As themanagement of the disease tends to be nonsurgical,staging is clinical rather than pathological. Severalstaging systems have been used over the past 20years, and the prognostic significance of various riskfactors is a complex issue. Early American JointCommittee on Cancer (AJCC) classifications (1977and 1992) for head and neck cancer typically resultedin a stage III or IV grouping for most nasopharyngealmalignancies, owing to the high incidence ofclinically involved neck disease (AJCC 1977, 1992). (Adetailed discussion on the staging of NPC is out ofthe scope of this chapter and is detailed in chapter 24.However, knowledge on evolution of the stagingespecially for early stage disease is partinent)In Asia, the Ho staging system (Ho 1972) is commonlyused, and may result in superior prognosticseparation of patient groups when compared with the1977 AJCC system or the 1967 Uniform InternationalCommittee on Cancer (UICC) system (Ho 1978; Teoet al. 1991). Because of the high incidence of lymphnode involvement with nasopharyngeal cancer, the Hosystem separates patients based on the level of lymphnode involvement (Table 10.1). The 1992 AJCC system,unchanged from AJCC 1977, included some patientswith N1 disease in stage III, but the remaining patientswith nodal involvement and metastases outside theneck were all grouped together into stage IV. Nodalinvolvement appears in stage II of the Ho system, andsupraclavicular metastases are represented in a separatestage IV (Table 10.1). The AJCC system now incorporatessome of the aspects of the Ho system (AJCC1998). The current AJCC system is superior to both theHo system and the previous AJCC system (Cooperet al. 1998; Au et al. 2003). Further refinement may leadto improvement in risk stratification. For example, T4patients with intracranial invasion or involvement ofthe orbit or cranial nerves have a poor prognosis (Auet al. 2003). However, the benefits of such refinementmust be weighed against the benefits of staging stabilityover time, simplicity, and accuracy of reporting.In the mid-1990s, data from several investigatorsindicated that lateral invasion into the parapharyngealspace was associated with higher risk of failure(Chua et al. 1996; Teo et al. 1996; Xiao et al. 2002).Such invasion is of increased prognostic significancein patients without other more significant risk factors,such as cranial nerve invasion or lymph nodepositivity. Parapharyngeal space invasion predicts fordecreased survival, disease-free survival, and localcontrol. The 1997 (and current) AJCC staging systemseparates T2 into T2a and T2b based on this riskstratification, and subsequent chemoradiation trialshave included T2bN0 patients. Between 75 and 90%of patients with T2 disease are stage T2b. Posteriorinvolvement of the parapharyngeal space (posteriorto the styloid process) portends a worse prognosis insome series, but this has not been consistentlyreported (Chua et al. 1996; Xiao et al. 2002). TheChinese staging system adopted in 1992 classifiesparapharyngeal involvement posterior to the styloidprocess as T3, while anterior involvement is T2 (Honget al. 2000; Ma et al. 2001). Retropharyngeal lymphnode involvement does not appear to be an independentrisk factor for recurrence (Chua et al. 1997).In reviewing the various staging systems, withregard to their impact on the definition of early stagedisease, one sees that the current AJCC system is similarto the Ho and Chinese system. The older AJCC systemswould classify patients with nasal cavity ororopharyngeal involvement as T3, while this is classifiedas T2 in the other systems. Thus, patients withsuch involvement treated on older trials using the