The recent recognition that the addition of concurrent chemotherapy to definitive radiation can improve locoregional control, organ preservation, and survival in patients with squamous cell head and neck cancer has had a significant impact on our management choices. Chemoradiotherapy data from metaanalyses, cooperative group trials, and large tertiary care institutions now suggest that there is a realistic potential for cure in almost all patients with locoregionally confined disease, and the focus has increasingly shifted toward the impact of our treatments on longterm function. In the past, control of neck node involvement often required a comprehensive neck dissection, a procedure associated with some degree of long-term morbidity. In this review, Kutler, Patel, and Shah address the important question of whether the neck dissection should be a planned component in the management of patients treated with definitive concurrent chemoradiotherapy.
Choosing Appropriate Patients
Their answer, and mine, is a clear yes. The problem, however, is choosing the appropriate patients. It seems quite clear, for example, that patients with clinically negative necks at presentation will not require neck dissection after definitive chemoradiotherapy and have little chance of regional recurrence. Similarly, patients with N1 disease who experience aclinical complete response to chemoradiotherapy will also rarely recur in the neck. On the other hand, if a patient has residual evidence of clinical disease in the neck after completion of nonoperative therapy, a neck node dissection is clearly indicated. This is the case despite the recognition that the majority of these patients have no residual pathologic evidence of disease at the time of surgery.
For the patient with truly bulky (N3) lymph node involvement at presentation, most investigators agree that a planned neck dissection will be required, particularly since the majority of these patients do not experience clinical clearing of their tumor after chemoradiotherapy. There are still, however, a large number of patients who present with an intermediate amount of neck involvement (N2a, b, or c) and who experience complete tumor clearance after chemoradiotherapy. Should a neck dissection be planned in their management?
Our data from the Cleveland Clinic Foundation[1] and data from other institutions,[ 2,3] would suggest that all such patients should undergo a planned neck dissection. In our experience, 25% of the patients who achieve a clinical complete response in the neck still have pathologic evidence of disease at the time of surgery. Furthermore, among those who achieve a clinical complete response in the neck and have not undergone neck dissection, the incidence of regional recurrence and death was 12%. We were unable to identify any clinical predictors for the achievement of a pathologic complete response in the neck, suggesting that the safest approach to recommend would be a neck dissection for all.
Another Perspective
The counterargument however, has also been made. The discordance between the pathologic positivity in theclinically negative neck (25% in our series) and the incidence of regional failure in the undissected patient (12% in our series) has been pointed out and attributed to the difference between pathologically visible and biologically viable tumor. While it is likely that the pathologist does identify "disease" in a specimen, which may not have the potential to result in tumor recurrence, this phenomenon does not help the clinician. At the present time, one can only assume that pathologically identified cancer left in situ poses a significant risk to the patient.
It has also been argued that it might be better to closely follow patients who achieve a complete clinical response, reserving a neck dissection for salvage at the time of regional recurrence. Unfortunately, this strategy has proven flawed. Patients experiencing regional failure after concurrent chemoradiotherapy have rarely been salvaged. Edema and scarring from chemoradiotherapy can be significant and will seriously hamper the accuracy of a clinical examination, thus hindering early detection of nodal recurrence. Clearly, we will do better if we can identify the patients most likely to recur in the neck who could benefit most from a planned neck dissection.
Clinical Predictors
What are the potential clinical predictors? The experienced clinician will note the radiosensitivity of a tonsil cancer and suggest that patients with a complete clinical response in the neck after chemoradiotherapy for a tonsil cancer can safely be observed. Our experience is that the primary tumor site was not a useful predictor of a pathologic complete response. Others have suggested that the size of the neck nodes is of value. Patients with N2 disease are clearly a heterogeneous group. Bilateral 1-cm lymph nodes from a mid-line pharyngeal primary (N2c) represent a very different clinical situation than multiple 4- to 5-cm ipsilateral nodes (N2b). The possible value of positron-emission tomography (PET) scanning and the potential role of molecular markers are of considerable interest and merit further investigation.
It should also be pointed out that the implication of a clinical complete response in the neck occurring after single-modality induction chemotherapy is very different than a complete response after concurrent chemoradiotherapy. A complete response to chemotherapy is a favorable prognostic sign for subsequent radiosensitivity.[ 4] The patient achieving a complete neck response to induction chemotherapy who then undergoes radiation is similar to the clinically N0 patient treated with definitive radiation therapy alone. Concurrent chemoradiotherapy is very different. Independent prognostic information about chemotherapy (and therefore radiation) responsiveness cannot be abstracted from such an approach.
Practical Considerations
The morbidity from a neck dissection remains a significant concern. However, the morbidity of the neck dissection reflects the extent of the neck dissection. It is currently unknown whether patients achieving a clinical complete response after concurrent chemoradiotherapy require a comprehensive neck dissection orwhether a more limited, selective dissection might be reasonable. Although the clinically negative neck may prove pathologically positive, the residual disease is rarely extensive and usually only microscopic.
Kutler et al propose that the neck dissection be accomplished 6 to 8 weeks following chemoradiotherapy in patients who achieve a complete response. There are several practical considerations here. Concurrent chemoradiotherapeutic regimens produce significant mucosal toxicity, complicating the evaluation for residual primary site disease. Ideally, the neck dissection should be accomplished at a time when a formal evaluation of the primary site can also be performed. If residual primary site disease is identified, the residual tumor and the neck can be addressed at the same time. Unfortunately, residual mucositis may well persist beyond the 6- to 8-week guideline suggested by these authors.
Conclusions
The authors have carefully summarized the relevant issues here. One cannot stress enough, however, the importance of the word "planned" in this discussion. Decisions about neck dosing for the radiation therapist are often based on the surgeon's plan for the neck. If surgery in the neck is not anticipated, the neck will be boosted. This boost will result in additional toxicity and can only increase morbidity if neck surgery is anticipated. Decisions about a neck dissectionshould be made at the time the original treatment plan is outlined and not at the time of response assessment.
Our concern about who merits a neck dissection after concurrent chemoradiotherapy reflects a welcome byproduct of our treatment success. Nonoperative approaches can now reproducibly result in long-term disease control in many of these patients, and our focus has shifted toward minimizing the morbidity of our interventions. Efforts must be directed toward identifying more reliable clinical or biologic markers for those clinical complete responders likely to benefit from neck surgery after concurrent chemoradiotherapy.
Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
