Selection of Patients Requiring Elective Treatment

No parameters have been established to identify patients reliably with clinically occult lymphatic metastasis. Most investigators have adopted an arbitrary cutoff of 10 to 15% incidence of occult nodal involvement to select patients requiring elective intervention. Decision analysis, based on the data from the available medical literature, suggests that a 20% risk should be the accepted threshold for providing treatment.18

The risk of occult regional lymphatic metastasis from primary squamous cell carcinomas of the upper aerodigestive tract can be assessed on the basis of anatomic location of the primary tumor, size, T stage, and histomorphologic characteristics (Table 3-1). In general, the risk of occult nodal metastasis increases from the anterior to posterior aspect of the upper aerodigestive tract (i.e. the lips, < 5%; oral cavity, 19 to 50%; oropharynx, 22 to 66%; and hypopharynx, 38 to 77%.1-3'19-22 For tumors of the larynx and pharynx, the risk of nodal metastasis increases as one progresses from the center of the laryn-gopharyngeal compartment to the periphery.2'3'22'23 The risk of occult regional lymph node metastasis from carcinoma of the true vocal cord is exceedingly small, increasing as one progresses from the vocal cords to the false vocal cords, aryepiglottic fold (16 to 26%), pyriform sinus (38%), and pharyngeal wall (66%).2,3,22,23 Within the oral cavity, a significantly higher risk of

TABLE 3-1

Risk Factors for Micrometastasis in Head and Neck Squamous Cell Carcinomas

Anatomic location Size T stage

Depth of invasion

Type of host-tumor interface

Endophytic growth pattern occult nodal metastases occurs in floor-of-mouth (40 to 50%), gingival (19%), and oral tongue cancers (25 to 54%) than those originating from the hard palate (<5%).2,3,22,23 The risk of occult nodal metastases increases with increasing primary tumor burden at any site, as reflected by the T stage. The risk of nodal metastasis increases from < 14% for T1 lesions to 30% for T2, 45% for T3, and 55 to 75% for T4 lesions. Occult involvement increases from 19% for T1 and T2 lesions to 26 to 32% of T3 and T4.1-3^24

Certain histomorphologic features of the primary tumor also predict an increased risk of nodal metastasis. Endophytic tumors are more inclined to metastasize than are exophytic tumors. It has been well documented that for tongue and floor-of-mouth cancers, tumor thickness is related to the risk of nodal metastases, with a 7.5% prevalence of occult metastasis for tumors < 2 mm thick compared with 26% for 2-8 mm tumors and 42% for those > 8 mm in thickness25 (Table 3-2). Similarly, Fukano and his colleagues showed clinically negative necks turned out pathologically positive in 30% of cases with < 5 mm depth of invasion, compared with 43% when the tumor depth was > 5 mm.26 Poorly differentiated carcinomas are associated with a higher risk of nodal metastasis compared with well-differentiated lesions. In addition, such factors as tumor-host interface have been suggested to be predictive of risk.27

Augmentation of clinical examination with various radiologic studies, including computed tomography (CT) (66%), magnetic resonance imaging (MRI) (75%), and ultrasound examination (68%), enhances the accuracy with which those patients who have nodal metastasis can be identified.28-39 Although a 92% accuracy rate for identifying cervical metastasis is reported with the use of positron emission tomography (PET) scanning, it is tainted by sample size constraints.38 The use of sentinel node biopsy and molecular assessment for occult metastasis also remains both limited and variable in efficacy.40-43 The presence of metastasis that is missed on routine pathologic examination is confirmed in studies using supplemental subse-rial sectioning, immunohistochemistry, or molecular analysis.

An additional 8% of cases with metastasis in regional lymph nodes were identified by Ambroch and Brink44 on serial sectioning of lymph nodes reported as negative on routine pathologic

TABLE 3-2

Relationship between Tumor Thickness and Development of Lymph Node Metastasis and Survival in Patients with T1 or T2 Oral, Tongue, and Floor-of-Mouth Carcinomas

With Lymph Node Dead of Disease

examination in NO necks. Most strikingly, Brennan et al.42 identified a 21% rate on missed lymphatic metastasis, using p53 mutation analysis. Finally, mathematical models, attempting to combine all available information, and molecular studies, attempting to identify patients at increased risk of occult metastasis, have also met with variable results.19'45 Overall, even with the use of supplemental studies, no reliable methods have been identified for accurate prediction of the presence of nodal metastasis in individual patients with clinically undetectable disease. Accordingly, selection of patients for elective treatment continues to be made on the basis of arbitrary criteria.

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