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REVIEW ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 3  |  Page : 1114-1116

Management of the neck in early oral cancers: Is the verdict out?


1 Department of Surgical Oncology, HCG Cancer Center, Head and Neck Services, Bengaluru, Karnataka, India
2 Department of ENT-Head Neck Surgery, Jawaharlal Nehru Medical College, KLE University, Belgaum, Karnataka, India
3 Department of Surgical Oncology, St. John's Medical College, Bengaluru, Karnataka, India

Date of Web Publication4-Jan-2017

Correspondence Address:
Vishal U. S. Rao
Department of Surgical Oncology, HCG Cancer Center, Head and Neck Services, #8 HCG Towers, P. Kalinga Rao Road, Sampangiram Nagar, Bengaluru - 560 078, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.164705

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 > Abstract 

The management of patients with the clinically negative neck (N0) in early oral cancers awaits a clear mandate despite growing evidence favoring elective neck dissection. Having a general policy of operating all N0 neck may indeed increase the number of unnecessary neck dissection in the true pathological N0 necks, a more commonly encountered scenario. This controversy needs to be looked beyond statistical evidence to address a larger question to “does the neck truly harbor disease,” thus, refining the early age old debate. This article highlights the feasibility of wait and watch policy, while elaborating a stringent algorithm to judiciously select patients in whom the neck may be safely observed.

Keywords: Metastasis, neck, oral cancer


How to cite this article:
Rao VU, Patil PH, Rajaram B V. Management of the neck in early oral cancers: Is the verdict out?. J Can Res Ther 2016;12:1114-6

How to cite this URL:
Rao VU, Patil PH, Rajaram B V. Management of the neck in early oral cancers: Is the verdict out?. J Can Res Ther [serial online] 2016 [cited 2017 Mar 22];12:1114-6. Available from: http://www.cancerjournal.net/text.asp?2016/12/3/1114/164705


 > Introduction Top


Treatment of the neck in oral cancer patients with clinically involved neck nodes is essential and well established. However, the treatment of patients with the clinically negative neck (N0) in early oral cancers remains controversial. The controversy is whether to treat the neck electively or to adopt a wait and watch policy followed by therapeutic neck dissection in the event of nodal recurrence. Therapeutic neck dissection is an attractive treatment option as up to 70% of the early oral cancers does not harbor disease in the nodes.[1] Therefore, these patients would not be subjected to an additional surgical procedure and the added morbidity and cost.

The proponents of elective neck dissection (END) have put forward the argument that surgery of the neck can lead to better disease control and improve survival with acceptable surgical morbidity.[2] END also provides better pathological staging, prognostication and can help in deciding adjuvant treatment.[3] The evidence for such an approach until now was mainly based on retrospective studies.

The recent meta-analysis by Fasunla et al.[4] has reignited this debate presenting more robust evidence to support END. Despite having certain drawbacks in this study (as discussed by D'Cruz and Dandekar), this study has provided a strong case to consider END over wait and watch policy.[5] Does this mandate that all early oral cancers need neck management despite a N0 neck?

We believe that there needs to be a change in the title of the debate from “whether the neck should be operated” to “does the neck truly harbor disease” thus refining the early age old debate. Having a general policy of operating all N0 neck may indeed increase the number of unnecessary neck dissection in the true pathological N0 necks. This article highlights the feasibility of wait and watch policy, while elaborating a stringent algorithm to judiciously select patients in whom the neck may be safely observed. Our discussion is elaborated under three headings:

  • Vigilant detection of clinical N0 neck using adjunct techniques
  • Incidence of neck metastasis in early oral cancers
  • Cautions with wait and watch policy and ideal follow-up algorithm.



 > Vigilant Detection of Clinical N0 Neck Using Adjunct Techniques Top


The quest toward more accurate detection of subclinical focus has led investigators to explore newer means to improve the rate of detecting this subclinical focus which include advanced imaging technologies, sentinel node biopsy coupled with molecular markers, or perform a staging neck dissection.

Sentinel node biopsy has been a novel tool in this regard with high rates of accuracy and a pickup rate of up to 90% and above when molecular markers were used.[6],[7] However, this technique is limited by its availability and costs, hence not making it an universally acceptable diagnostic tool.

Various imaging modalities have been evaluated which include the ultrasound (US), computed tomography (CT) scan, magnetic resonance imaging, positron emission tomography scan, and the US guided fine needle aspiration cytology (US-FNAC). A recent meta-analysis to evaluate the ideal imaging modality concluded US-FNAC to be the investigation of choice with high sensitivity, specificity, and diagnostic odds ratio.[8] Hence, it is obvious that most desirable option would be to determine if the clinically N0 neck harbors a subclinical focus of nodal metastasis.

With the existing options, US-FNAC balances the accuracy with cost and availability and could be the investigation of choice followed by sentinel node biopsy.


 > Incidence of Neck Metastasis in Early Oral Cancers Top


Weiss et al. based on a mathematical model suggested elective neck treatment for patients where the propensity for neck metastasis was more than 20%.[9] To predict this probability, several parameters have been used which include high-risk sites (oropharynx, hypopharynx), stage, adverse tumor features (lymphovascular emboli, perineural invasion). Although the above parameters do predict biological aggressiveness of the tumor, they fail to accurately predict the percentage probability.

However, the data from the four randomized control trials (RCTs) on early oral cancers with N0 neck clearly shows that the nodal failure rates in the observation arm in these studies were (53%, 58%, 39%, and 37%, respectively).[10],[11],[12],[13] Unfortunately, the incidence of positive necks in clinical N0 necks in neck dissection specimens may not give us the true rate of positive neck nodes unless close sectioning of the specimen was performed. This sampling error is obvious even in some of the RCT where the neck failure in wait and watch arm is more than 10% higher to node positivity in the END arm (33% vs. 57.5%,[11] 21% vs. 39%,[12] 22% vs. 37%).[13] Yuen et al. showed that 36% of the patients with early tongue cancer and clinically N0 neck did have a subclinical focus on performing close sections (3 mm) of the neck dissection specimen.[14] Van den Brekel et al. have reported that in END of clinically N0 necks, micrometastases (<3 mm) occurred in 25% of patients.[15]

Hence, it is evident with the above data that early oral cancers especially of the oral tongue have a high propensity for regional metastasis (possibly more than 20%) and hence may mandate an END. It is also interesting to note that all the patients in these RCT had oral tongue or floor of the mouth as their primary site and none with buccal mucosa cancers. The feasibility of observation when dealing with buccal cancers may be answered in the RCT (NCT 00193765) which includes early buccal cancers.


 > Cautions With Wait and Watch Policy and Ideal Follow-Up Algorithm Top


We strongly believe that although wait and watch policy is a viable option in the management of neck for early oral cancers, this decision needs to be taken by an oncologist bearing all the issues surrounding this policy.

  • Patient compliance and social factors: The important aspects to employing a wait and watch policy are patient compliance and the infrastructure to follow-up these patients. Various social factors are involved in determining the compliance of a patient. These factors include age, education, socioeconomic status, and distance from the hospital to cite a few. Certain studies from high volume centers indicate that compliance of patients is not satisfactory, which may be a cause for concern. A study from a high volume cancer center in India found that the compliance of head and neck cancer patients for treatment was 56% (1209 out of 2167)[16]
  • Robust follow-up regimen: van den Brekel et al. have reported their experience on use of palpation and US-FNA in the follow-up of patients being observed. They detected metastases in 14 of 77 (18%) patients of whom 10 (71%) were successfully salvaged. The follow-up regimen they followed was palpation every 4–8 weeks and US-FNA every 2-5 follow-up visits in the 1st year with intervals gradually increased in the 2nd year. The authors mention that this regimen would increase the workload of the outpatient clinic, but is very essential if a wait and watch policy is being implemented [17]
  • Patient needs to be counseled that although no clear evidence of survival detriment, up to 23% of them will present in a inoperable stage [18]
  • Morbidity of salvage surgery: Those patients who have neck failure after observation will necessarily need a radical neck dissection as compared to selective or modified radical neck dissection with an occult metastasis. This greatly increases the morbidity while diminishing the quality of life. Andersen et al. studied the results of neck failure following observation of N0 necks. They found that 60% of patients had N2 disease and 49% had extracapsular spread (ECS).[1] Either or both these adverse prognostic factors were present at the time of surgery in 77% of patients. Studies by Ho et al. and Kowalski et al. found that the salvage rates for recurrences were 30% and 50%, respectively.[19],[20] The results of these studies show that the recurrences that occur following observation are of a higher stage with poor prognostic features in majority of patients. Therefore, implying that surgery (if feasible) for recurrence would have to be more extensive than a selective neck dissection and, therefore, the morbidity associated would be higher
  • Added costs of treatment, hospital stay, and other expenses further compound the existing issues
  • Data from the more recent RCT [13] would suggest that even though ECS was higher in patients with recurrent disease, all patients were salvaged and there was no difference in survival as compared to END group. The authors hypothesize that even though there was ECS, because the patients were on close follow-up with clinical and US evaluation, they may have been identified at an early stage. They suggest that wait and watch policy should not be rejected merely on the risk of nodal recurrence with ECS. They avoided radiotherapy for patients with recurrent disease with pN1 status, thereby avoiding the added cost and adverse effects of radiation.


Thus any conscious decisions to observe the neck needs to take into account the above issues and discussing it with the patient and family.

An ideal algorithm for patients with N0 neck being observed should consist of a very stringent follow-up consisting of clinical and radiological (US or CT scan) evaluation 3–4 weekly with FNAC of any suspicious nodes for at least 2 years followed by 2–3 monthly follow-up for 5 years. All patients with clinical and radiological N0 neck with doubtful compliance should be strongly considered for neck dissection or radiotherapy, based on the treatment modality used for primary cancer.


 > Conclusion Top


The recent literature shows some strong evidence supporting END for early oral cancers with N0 neck. We believe that there needs to be a change in the title of the debate from “whether the neck should be operated” to “does the neck truly harbor disease” thus refining the early age old debate. US-FNAC and sentinel node biopsy are the best noninvasive and invasive modality at present to assess the status of the neck. The optimal management of early oral cancers with N0 neck should incorporate aggressive neck management. Wait and watch policy is an attractive alternative to END and should be advocated only in patients who are compliant for a very close follow-up regimen.

 
 > References Top

1.
Andersen PE, Cambronero E, Shaha AR, Shah JP. The extent of neck disease after regional failure during observation of the N0 neck. Am J Surg 1996;172:689-91.  Back to cited text no. 1
    
2.
Pitman KT. Rationale for elective neck dissection. Am J Otolaryngol 2000;21:31-7.  Back to cited text no. 2
    
3.
Ferlito A, Silver CE, Rinaldo A. Elective management of the neck in oral cavity squamous carcinoma: Current concepts supported by prospective studies. Br J Oral Maxillofac Surg 2009;47:5-9.  Back to cited text no. 3
    
4.
Fasunla AJ, Greene BH, Timmesfeld N, Wiegand S, Werner JA, Sesterhenn AM. A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck. Oral Oncol 2011;47:320-4.  Back to cited text no. 4
    
5.
D'Cruz AK, Dandekar MR. Elective versus therapeutic neck dissection in the clinically node negative neck in early oral cavity cancers: Do we have the answer yet? Oral Oncol 2011;47:780-2.  Back to cited text no. 5
    
6.
Paleri V, Rees G, Arullendran P, Shoaib T, Krishman S. Sentinel node biopsy in squamous cell cancer of the oral cavity and oral pharynx: A diagnostic meta-analysis. Head Neck 2005;27:739-47.  Back to cited text no. 6
    
7.
Stoeckli SJ, Alkureishi LW, Ross GL. Sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol 2009;266:787-93.  Back to cited text no. 7
    
8.
de Bondt RB, Nelemans PJ, Hofman PA, Casselman JW, Kremer B, van Engelshoven JM, et al. Detection of lymph node metastases in head and neck cancer: A meta-analysis comparing US, USgFNAC, CT and MR imaging. Eur J Radiol 2007;64:266-72.  Back to cited text no. 8
    
9.
Weiss MH, Harrison LB, Isaacs RS. Use of decision analysis in planning a management strategy for the stage N0 neck. Arch Otolaryngol Head Neck Surg 1994;120:699-702.  Back to cited text no. 9
    
10.
Vandenbrouck C, Sancho-Garnier H, Chassagne D, Saravane D, Cachin Y, Micheau C. Elective versus therapeutic radical neck dissection in epidermoid carcinoma of the oral cavity: Results of a randomized clinical trial. Cancer 1980;46:386-90.  Back to cited text no. 10
    
11.
Fakih AR, Rao RS, Patel AR. Prophylactic neck dissection in squamous cell carcinoma of oral tongue: A prospective randomized study. Semin Surg Oncol 1989;5:327-30.  Back to cited text no. 11
    
12.
Kligerman J, Lima RA, Soares JR, Prado L, Dias FL, Freitas EQ, et al. Supraomohyoid neck dissection in the treatment of T1/T2 squamous cell carcinoma of oral cavity. Am J Surg 1994;168:391-4.  Back to cited text no. 12
    
13.
Yuen AP, Ho CM, Chow TL, Tang LC, Cheung WY, Ng RW, et al. Prospective randomized study of selective neck dissection versus observation for N0 neck of early tongue carcinoma. Head Neck 2009;31:765-72.  Back to cited text no. 13
    
14.
Yuen AP, Lam KY, Chan AC, Wei WI, Lam LK, Ho WK, et al. Clinicopathological analysis of elective neck dissection for N0 neck of early oral tongue carcinoma. Am J Surg 1999;177:90-2.  Back to cited text no. 14
    
15.
van den Brekel MW, van der Waal I, Meijer CJ, Freeman JL, Castelijns JA, Snow GB. The incidence of micrometastases in neck dissection specimens obtained from elective neck dissections. Laryngoscope 1996;106:987-91.  Back to cited text no. 15
    
16.
Mohanti BK, Nachiappan P, Pandey RM, Sharma A, Bahadur S, Thakar A. Analysis of 2167 head and neck cancer patients' management, treatment compliance and outcomes from a regional cancer centre, Delhi, India. J Laryngol Otol 2007;121:49-56.  Back to cited text no. 16
    
17.
van den Brekel MW, Castelijns JA, Stel HV, Golding RP, Meyer CJ, Snow GB. Modern imaging techniques and ultrasound-guided aspiration cytology for the assessment of neck node metastases: A prospective comparative study. Eur Arch Otorhinolaryngol 1993;250:11-7.  Back to cited text no. 17
    
18.
D'Cruz AK, Siddachari RC, Walvekar RR, Pantvaidya GH, Chaukar DA, Deshpande MS, et al. Elective neck dissection for the management of the N0 neck in early cancer of the oral tongue: Need for a randomized controlled trial. Head Neck 2009;31:618-24.  Back to cited text no. 18
    
19.
Ho CM, Lam KH, Wei WI, Lau SK, Lam LK. Occult lymph node metastasis in small oral tongue cancers. Head Neck 1992;14:359-63.  Back to cited text no. 19
    
20.
Kowalski LP, Bagietto R, Lara JR, Santos RL, Silva JF Jr, Magrin J. Prognostic significance of the distribution of neck node metastasis from oral carcinoma. Head Neck 2000;22:207-14.  Back to cited text no. 20
    




 

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