Changing concepts in the surgical management of the cervical node metastasis

TY - JOUR

T1 - Changing concepts in the surgical management of the cervical node metastasis

AU - Ferlito, Alfio

AU - Rinaldo, Alessandra

AU - Robbins, K. Thomas

AU - Leemans, C. René

AU - Shah, Jatin P.

AU - Shaha, Ashok R.

AU - Andersen, Peter E.

AU - Kowalski, Luiz P.

AU - Pellitteri, Phillip K.

AU - Clayman, Gary L.

AU - Rogers, Simon N.

AU - Medina, Jesus E.

AU - Byers, Robert M.

N1 - Funding Information: Alfio Ferlito a ∗ a.ferlito@dsc.uniud.it Alessandra Rinaldo a K. Thomas Robbins b C. René Leemans c Jatin P. Shah d Ashok R. Shaha d Peter E. Andersen e Luiz P. Kowalski f Phillip K. Pellitteri g Gary L. Clayman h Simon N. Rogers i Jesus E. Medina j Robert M. Byers h a Department of Otolaryngology—Head and Neck Surgery, University of Udine, Policlinico Universitario, Piazzale S. Maria della Misericordia, I-33100, Udine, Italy b Gainesville, FL, USA c Department of Otolaryngology—Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands d Head and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA e Department of Otolaryngology, Oregon Health and Science University, Portland, OR, USA f Head and Neck Surgery and Otorhinolaryngology Department, Centro de Tratamento e Pesquisa Hospital do Cancer A. C. Camargo, São Paulo, Brazil g Department of Otolaryngology-Head and Neck Surgery, Geisinger Medical Center, Danville, PA, USA h Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA i Department of Oral and Maxillofacial Surgery, University Hospital Aintree and Liverpool University Dental Hospital, Liverpool, UK j Department of Otolaryngology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA ∗ Corresponding author. Tel.: +39-0432-559302; fax: +39-0432-559339 The management of regional lymph nodes in the neck is an important subject since the presence of clinically palpable cervical lymph node metastasis decreases the overall survival in head and neck squamous cell carcinoma (HNSCC) by approximately 50%. 1–5 With the exception of distant metastases, the presence of cervical lymph node metastasis is the single most adverse independent prognostic factor in HNSCC. Cervical lymph node metastases may be subdivided into two categories: overt nodal disease (clinical metastases) and non-overt nodal disease (occult or subclinical metastases). There are two classes of occult metastases. 6 The first consists of occult metastases identified by “established” or traditional methods. These are metastatic deposits small enough to evade detection on clinical or radiographic examination using the most sensitive and technologically advanced procedures, 7–9 but that are detected by light microscopy. The incidence of these established occult metastases varies with the location, size and thickness 10 of the primary tumor. A second class of occult metastases may be designated “subpathological” or “submicroscopic”, because they are too small to be detected by light microscopy on hematoxylin and eosin-stained slides, 6 but may be detected in the pathologically dissected lymph nodes by means of immunohistochemistry and/or molecular analysis. 11–16 These newer techniques are capable of converting the status of nodes from negative (as assessed by conventional microscopy and sampling) to positive (as previously undetected micrometastases are revealed by way of these more sensitive detection methods). 8 Even though these techniques are not used in regular clinical practice, there appears to be tremendous interest in these approaches to enhance detection. It is yet to be determined what, if any, impact the detection of submicroscopic occult lymph node metastases will have on the recurrence rates or survival in patients with HNSCC, and whether patients with such disease should have adjuvant treatment with radiation therapy. It is possible that the presence of submicroscopic occult nodal metastasis explains the curious and frustrating clinical scenario of the patient who is initially staged N0 both clinically and pathologically yet subsequently suffers recurrence in the dissected neck. The use of newer and more sensitive means of evaluation and serial sections of lymph nodes have led to varied interpretations and different applications of the TNM system. 15 This topic deserves further investigation. Historically, the treatment of patients with clinically palpable metastatic disease (overt nodal disease) in the neck has been radical neck dissection (RND). This procedure involves the removal of all lymph nodes in the dissected side of the neck along with sternocleidomastoid muscle, internal jugular vein, spinal accessory nerve, submandibular salivary gland, tail of parotid gland and cutaneous branches of the cervical plexus as described by Crile 17 nearly 100 years ago and later popularized by Martin et al. 18 Although Crile 17 stated that “… an incomplete operation disseminates and stimulates the growth, shortens the life, and diminishes comfort… the logical technique is that of a “block” operation… as Halsted operation…” , in the series reported, only 46 patients had radical block dissections and 86 had more selective procedures, similar to a supraomohyoid neck dissection. However, this time-honored surgical procedure produces significant postoperative morbidity with typical shoulder dysfunction and limitations in its application to bilateral cervical fields. 19 Ward and Robben 20 were possibly the first to describe in the 1950s that the neck dissection could be modified by sparing the spinal accessory nerve whenever possible to prevent postoperative shoulder drop. Later, Saunders et al. 21 compared the functional results of cases that underwent neck dissection with sacrifice, preservation or reconstruction (cable graft) of the spinal accessory nerve, demonstrating that shoulder symptoms were only mild or moderate in more than 80% of the patients that had the nerve preserved or cable grafted. A significant problem is the treatment of patients with bilateral neck metastasis at diagnosis. Severe complications that can be fatal can be reduced by performing this operation in two stages. A recent publication of a series of 192 patients that underwent bilateral neck dissections with preservation of one or both internal jugular veins showed that the complication rates are acceptable and postoperative mortality can be reduced to 2.7%. In this paper it was shown that the preservation of the internal jugular vein in selected cases does not jeopardize the prognosis. 22 The preservation of the internal jugular vein has been performed and encouraged specially in patients submitted to microvascular reconstruction. In those cases, not only the internal jugular vein but usually the thyrolingual branch is preserved to facilitate the venous anastomosis. Currently there is mounting evidence to indicate that RND should not be the only surgical option for the clinically positive neck. 23 Functional neck dissection (FND), described in the early 1960s by Suárez, 24 and modified radical neck dissection (MRND) 1 are adequate surgical options for metastatic lymph nodes without gross extranodal extension of metastatic disease. Although the two procedures are quite similar, level I is typically preserved in the FND. 25 The efficacy of these types of neck dissections is comparable to that of RND, particularly when combined with postoperative radiation therapy. 26 In the 1980s, approaches to the management of the cervical lymphatics broadened to include further modifications of neck dissection. These limited neck dissections are termed selective neck dissections and constitute a further development of FND. One of the initial proponents of selective neck dissection (SND) was Ballantyne, 27 from M.D. Anderson Cancer Center, University of Texas, Houston. SND refers to cervical lymphadenectomy in which there is resection of select group of lymph nodes, leaving other nodes behind that are routinely removed in the RND. 28 The lymph node groups removed are based on the pattern of metastases, which are predictable relative to the primary site of cancer. Therefore, various SNDs are described in the updated classification proposed by the American Head and Neck Society and the American Academy of Otolaryngology—Head and Neck Surgery. 28,29 Kuntz and Weymuller 30 analyzed quality of survival of patients that underwent RND, MRND or SND. One year after the operation, the quality of life of the patients submitted to a MRND were similar to those submitted to a SND, and both groups had a better outcome than the patients submitted to a RND. The support for application of SND depends on the concept that classic anatomic, pathologic and clinical investigations 31–41 and recent prospective studies 42,43 have demonstrated that cervical lymph node metastases occur in predictable patterns in HNSCC. The absence of retrograde flow from the jugular nodes into the spinal chain may explain why metastatic spread to the posterior triangle is uncommon. The lack of drainage to the posterior cervical triangle has been postulated to be due to the presence of lymphatic valves in the cervical lymphatics. 44,45 A review of 1277 patients undergoing RND for HNSCC at Memorial Sloan-Kettering Cancer Center in New York identified positive lymph nodes in the posterior triangle in only 3% of instances, with a slight increase to only 5% when clinically positive lymph nodes were evident. 46 The compartmentalization of the cervical lymphatics and the concept that HNSCC tends to metastasize to the cervical lymphatics in a predictable fashion does not support the routine removal of all cervical lymph node groups, as performed in MRND and RND. Clinically, SND has been most utilized for elective treatment of the regional lymphatics when the risk of metastases is high. Results of this strategy indicate that regional control and survival rates are similar to those of more extensive neck dissections. 42,43,47–56 There is substantial evidence that micrometastases cannot be detected at present by non invasive methods, 7 so it is essential to dissect the neck in order to reduce the rate of regional recurrence and its related mortality. SND thus also serves as a staging procedure and can be used for decision making regarding the need for adjuvant postoperative radiation therapy. This type of surgical dissection appears to be supported by pathological, subpathological and clinical data. 57 Even microscopic extracapsular spread is of critical importance 58 and must be sought especially in small volume metastatic disease. 59 Pathological studies of lymph node metastases suggest that it is also logical to use SND in some patients with clinically obvious cervical lymph node metastasis. 44,50,52,55 When indicated, application of postoperative radiation therapy further reduces the rate of regional failure in patients following SND. Combining reports of SND in the N+ neck gives a mean recurrence rate of 8.3% (5.5–11.1%). 28,60 These data are comparable to reported recurrence rates after MRND or RND 1,61–66 although absolute comparison is difficult because the SND patients represented a more selected sample. 57 The use of SND for the clinically positive neck remains controversial but its efficacy has recently been demonstrated in HNSCC in a retrospective review by German authors. 67 With respect to regional control, their results with SND with or without postoperative radiotherapy were comparable to the results reported after MRND or RND with or without postoperative radiotherapy. With respect to overall survival, it seems possible that the addition of postoperative radiotherapy does improve the survival of patients with a generally poor prognosis. In 2002, Andersen et al. 44 reported a 10-year multi-institutional retrospective review of pooled data from 106 previously untreated clinically and pathologically node-positive patients undergoing 129 SNDs and followed for a minimum of 2 years or until patient death. Regional metastasis was clinically staged as N1 in 58 patients (57.7%), N2a in 5 (4.7%), N2b in 28 (26.4%), N2c in 14 (13.2%), and N3 in 1 (0.9%). Extracapsular extension of the tumor was detected pathologically in 36 patients (34.0%), and postoperative radiation therapy was administered to 76 patients (71.7%). Overall, nine patients experienced disease recurrence in the neck. Six of these recurrences were in the areas of the neck that had been dissected during the SND, for a regional control rate of 94.3%. The authors concluded that these results support the use of SND in carefully selected patients with clinically positive nodal metastasis from HNSCC. Regional control rates comparable to those achieved with comprehensive neck dissections could be achieved in appropriately selected patients. The main advantages of the use of SND are that surgical time is shortened and morbidity, especially with regard to shoulder dysfunction, is decreased. SND is now the preferred surgical management in elective treatment of cervical lymph nodes. In a select group of patients with N+ disease, the SND is also rapidly gaining similar support. 68 Of course, classical SND is not indicated in the presence of macroscopic extracapsular spread and infiltration of the fascial compartments of the neck or when there is evidence of fixed massive adenopathy to the common carotid artery. Among patients previously treated with radiotherapy or other types of neck surgery, 44,69,70 most surgeons prefer to perform more RNDs when salvage surgery is feasible. However, there are also some recent data to support the use of SND as part of the planned treatment for patients with bulky neck disease who received definitive radiation therapy or chemoradiation. 71,72 Nigauri et al. 73 failed to find evidence of skip metastases outside levels II–III among 217 patients with squamous cell carcinoma of the oropharynx treated with radiation therapy. These authors recommended SND for patients with N1 disease whereas MRND or RND was recommended for patients with N2-3 disease. Boyd et al. 74 analyzed 25 patients with squamous cell carcinoma of the oropharynx, nasopharynx, hypopharynx, and supraglottic larynx treated with radiation therapy. Among the 28 necks dissected (all but one had N2-3 disease), only 1/28 had tumor outside levels II–IV. Based on this, the authors recommended SND for patients of all pharyngeal sites requiring salvage/planned neck surgery following radiation therapy. Efficacy of targeted chemoradiation and planned SND to control bulk nodal disease in advanced neck cancer has been reported by Robbins et al. 75 Also, Clayman et al. 76 have used SND after chemoradiotherapy for oropharyngeal cancer in patients with advanced nodal disease. Thus, it may be that in the future SND will play a more definitive role in the overall management of patients with initial bulky neck node disease with head and neck cancer treated with non-surgical modalities but further evidence is warranted. 73 A potentially powerful adjunct to surgical treatment of the neck is lymphoscintigraphy and sentinel lymph node biopsy. This technique, which was pioneered by Morton et al. 77 for use in detecting lymphatic spread of cutaneous melanoma, capitalizes on the ability of nuclear radiography to identify primary, secondary and tertiary echelons of lymphatic drainage basins and to identify the index or “sentinel” lymph node associated with primary regions within the head and neck. It is minimally invasive and possesses the capacity to accurately stage the clinically occult neck in a number of different neoplasms. 78 Linking this diagnostic/staging modality to lymphadenectomy or other elective treatment of the neck in HNSCC represents an attractive concept which has recently been explored by Pitman et al. 79 at the University of Pittsburgh. These investigators examined the feasibility of identifying the sentinel lymph node in primary echelons of drainage from known HNSCC primary neoplasms though lymphoscintigraphy and sentinel lymph node biopsy, thus enabling one to stage the N0 neck in a minimally invasive manner and direct elective neck therapy accordingly. Based upon findings with both N0 and N+ patients, the investigators felt that lymphoscintigraphy and sentinel lymph node biopsy would offer not only the ability to stage neck disease but would also provide information as to the presence of atypical basins of lymphatic flow from upper aerodigestive tract primary sites which are not predictable and would not typically be addressed by the more classic anatomic regions outlined for SND. Accordingly, patients undergoing this procedure would have lymphatic flow patterns uniquely defined according to neck anatomy and the effects of previous treatment. Further, findings from the study suggested that lymphoscintigraphy in the N+ or previously treated neck demonstrated the potential for defining unpredictable cervical nodal levels at risk for metastasis. Studies such as this indicate that the use of sentinel lymph node biopsy in the treatment of HNSCC may ultimately provide the surgeon with the ability to adequately stage the N0 neck and direct elective therapy or assess the neck with recurrence in a minimally invasive manner in order to determine the extent of salvage required. The place of sentinel lymph node biopsy—in terms of avoiding a neck dissection at all—remains inadequately defined at this time in terms of therapeutic efficacy, practical application, and health-related quality of life. Sentinel lymph node biopsy in HNSCC is probably best considered an investigational technique—as such, it has not yet achieved the status of “standard of care” for the treatment of head and neck carcinoma patients. 80 The philosophy of neck dissection is changing or evolving 81–85 as surgeons realize that more extensive surgery does not equate to a better oncologic outcome. The goal will be to understand that less can often mean more. Of course, this is not always possible but we have to make every effort to focus on quality of life issues and to target our surgical expertise to only eradicate the cancer. Patients with head and neck cancer represent a unique challenge in terms of our ability to preserve cosmetic appearance and function while, at the same time, integrating multidisciplinary therapy. 69 Contemporary approaches to neck surgery have evolved to include modifications of classical RND involving preservation of non-lymphatic structures and avoiding dissection of lymph node groups not at risk of having metastases. 86 Although there is subjective morbidity following RND 30 and the dysfunction following a SND, as is relatively less important as other head and neck domains such as chewing, speech and swallowing, 87 survival is the primary concern of patients. 88,89 In the treatment of head and neck cancer patients pursuit for cure and survival is paramount and the majority of patients cope and come to terms with side-effects of treatment. 90 From the quality of life perspective conservative management that promotes quality of life must be weighed against survival considerations. The philosophy of management of metastatic disease in the neck has changed considerably over the last few decades with a better understanding of the patterns of nodal metastasis, understanding of the importance of extranodal spread, subclassification of the levels of the lymph node metastasis such as Ia, Ib, IIa, IIb, and Va and Vb, understanding of SND and MRND and special reference to preservation of the spinal accessory nerve for better functional outcome. The RND which was a standard of care for almost three quarters of a century has been essentially replaced by SND and MRND with appropriate use of postoperative radiation therapy. Clearly, the issues of quality of life and function have played an important role in the overall management of head and neck cancers. 91 Our concepts of surgical management of cervical node metastasis have changed considerably over the last quarter of a century and still these concepts are evolving. The role of ultrasound, ultrasound-guided needle biopsy, and sentinel node biopsy are still being evaluated. 80,92 Whether these special techniques will make a major impact in the overall management of cervical node metastasis remains to be seen. The current indications for classical RND are patients with N3 neck disease 93 not allowing the preservation of the spinal accessory nerve, multiple positive lymph nodes involving the spinal accessory nerve and/or the internal jugular vein, extensive residual or recurrent neck disease after radiotherapy and grossly extranodal spread. Modifications such as preservation or cable grafting of the spinal accessory nerve are done very frequently in most institutions, but the preservation of the internal jugular vein is considered critical only when performing a simultaneous bilateral neck dissection in patients with extensive bilateral disease. Prospective randomized studies of clinical outcomes of SND with and without postoperative radiation therapy from several large centers will be an exciting and desirable undertaking. The integration of immunohistochemical and molecular pathologic analysis into contemporary pathologic staging will determine the biologic impact of these new observations as we continue to increase our understanding of metastases and their management.

PY - 2003/7

Y1 - 2003/7

UR - http://www.scopus.com/inward/record.url?scp=0037566882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037566882&partnerID=8YFLogxK

U2 - 10.1016/S1368-8375(03)00010-1

DO - 10.1016/S1368-8375(03)00010-1

M3 - Review article

C2 - 12747966

AN - SCOPUS:0037566882

SN - 1368-8375

VL - 39

SP - 429

EP - 435

JO - Oral Oncology

JF - Oral Oncology

IS - 5

ER -