Abstract

Background.  Elderly patients over 80 years of age represent a growing population, some of whom have complex medical problems that are compounded by the presence of upper aerodigestive tract cancer.

Method.  Forthy three patients, aged 80 years and older, who were initially seen with head and neck squamous cell carcinoma from 1986 to 1992 at a tertiary care center were compared with 79 similar patients, aged 65 years or younger, in a retrospective, case-control study. 

Results.  Median overall survival for the patients over 80 years of age was significantly lower than that for the controls (p = 0.001).  However, their overall survival was similar to the actuarial survival for the general octogenarian population.  Advanced age also adversely affected local control (p < 0.001) and disease-specific survival (p = 0.041).  Although the older age group had a higher frequent of morbid preoperative conditions, there were no significant differences in perioperative or postoperative complications between the two groups. 

Conclusions.  Careful preoperative staging and evaluation of associated medical illnesses, as well as skillful perioperative and postoperative management, are essential for reducing operative morbidity and mortality in the octogenarian patients.  Successful outcome depends upon appropriate surgical management, treatment of concurrent illnesses, and minimization of postoperative complications.  Individualized surgical management of the elderly head and neck cancer patient is effective, well tolerated, and clinically indicated for upper aerodigestive tract malignancies. 1998 John Wiley & Sons. Inc. Head Neck 20: 216-223, 1998.

Key words: elderly; head and neck; cancer; squamous cell; age

In the United States, elderly individuals represent the most rapidly growing subset of the population. Currently, the elderly constitute 30% of the population, with an anticipated 10% increase in this age group by the year 2000 (1).  At the turn of the century, it is estimated that there will be 10 million people who are 80 years of age or older.  The increasing populace aver the age of 85 years already consumes more than twice the Medicare dollars that are consumed by the 65 to 69 year age group, which profoundly influences the United States' health-care expenditures (2).

Several studies have been carried out to determine the relative safety of anesthesia and surgery in the elderly individual.  Only a handful of studies have addressed this issue for surgery in the head and neck.  Although the perioperative mortality rate varies with the type of procedure performed, it appears that head and neck surgery has a lower mortality rate in the aged than elective surgery in other anatomic regions (3). 

To determine the potential benefit of surgical intervention in the octogenarian head and neck cancer patient, analysis of surgical outcomes is required.  Although perioperative mortality rates for elderly patients have decreased, the long-term benefit for these patients is unknown.  The hypothesis of this study is that octogenarians with head and neck squamous cell carcinoma are hardy patients who have withstood the test of time and therefore should undergo curative, ablative surgery when possible.  We now report the perioperative morbidity and mortality and long term outcomes of 43 consecutive patients, 80 years of age and older, with squamous cell carcinoma (SSC) of the upper aerodigestive tract who underwent major ablative surgery form 1986 to 1992.

MATERIALS AND METHODS

A retrospective analysis of 43 patients who were = or > 80 years of age and underwent surgical resections of upper aerodigestive tract SCC between 1986 and 1992 (group I) was performed.  Only patients who required general anesthesia and underwent major ablative surgery at the University of Texas M. D. Anderson Cancer Center were assessed.  Patients who underwent less extensive procedures, such as tracheostomy or resection of lip and skin malignancies, were excluded.

For comparison, a second control population of patients who were 65 years of age or younger and underwent surgical treatment for upper aerodigestive tract SCC (group 2) was selected by computer.  Approximately two controls were matched to each octogenarian patient according to sex, race, and site and stage of the primary tumor.

Preoperative Health Status.  Preoperative medical condition and risk factor were determined by individual chart review for both patient groups.  All patients had undergone a preoperative medical evaluation by their head and neck surgeon, internist and/or cardiologist, and anesthesiologist; hematologic, radiographic, pulmonary, and cardiac studies had been performed ad indicated.  Hypertension, coronary artery or valvular heart disease, chronic obstructive pulmonary disease, diabetes mellitus, and other systemic disorders were considered to be present if the patient had been diagnosed with the condition prior to surgery.  Previous myocardial infarction was defined as the presence of Q waves of at least 0.04 seconds in duration and 1 mm deep on a preoperative electrocardiogram EKC).  Tobacco and alcohol histories were also recorded.  Based on the results of the preoperative evaluation, the health status for each patient was classified during the preanesthetic assessment according to the American Society of Anesthesiologists (ASA) Classification of Physical Status system (2).   

Postopereative Morbidity and Mortality.  Complications that occurred within the first 24 hours during or following surgery were considered to be early, whereas those that occurred within 2 weeks postoperatively were considered delayed.  Serious complications included the following: (1) myocardial infarction, defined as either the new appearance of a significant Q wave on EKG or an elevated serum creatinine phosphokinase MB fraction consistent with myocardial infarction in two independent, time-course assays; (2) pulmonary embolus, diagnosed by a high-probability nuclear ventilation-perfusion scan or by pulmonary angiography; (3) central nervous system morbidity, defined as a newly documented cerbrovascular accident, transient or reversible neurological deficit, or neurological deficit of any origin, including those related to ethanol withdrawal; (4) respiratory failure, defined as the necessity for mechanical ventilation for greater than 24 hours following surgery (36 hours if free tissue transfer was performed) or the need to reintubate and ventilate following discontinuation of mechanical ventilation.

Statistical Analyses.  Total lengths of hospitalization for the two groups were compared using a two-tailed student's test.  Operative morbidity, histologic findings, and disease recurrence were compared using a chi-square test, and the total anesthesia time for the groups was compared using the Mann-Whitney rank sum test.  Expected patient survival was computed for persons of like sex and calendar year of birth based on cohort life tables constructed for the Southwest Central Region of the United States.  Local disease control, disease-specific survival, and overall survival were analyzed using the method of Kaplan and Meier.  All patients were followed up for survival until time of death or study termination.  The statistical analysis was performed using the SPSSPC (SPSS Inc., Chicago, IL), BMDP (BMDP Statistical Software Inc., Los Angeles, CA), and Sigma Stat (Jandel Corporation, San Rafael, CA) software programs.

RESULTS

Patient Characteristics.   All patients had biopsy-proven SCC of the upper aerodigestive tract and were staged according to the American Joint Committee on Cancer (4).  The majority of the patients in both groups had oral cavity primaries (60.5% and 65.8%, respectively); the remainder had primary tumors that were evenly distributed between the pharynx and larynx.

Group 1 consisted of 43 patients, of whom 23 (53%) were men and 20 (47%) were women; the median age was 83 years (range, 80-93 years).  Eight patients had undergone surgery other than biopsy prior to evaluation, 4 had undergone radiotherapy alone or in combination with surgery, and 1 had received chemotherapy.  Group 2 consisted of 79 patients, of whom 49 (62%) were men and 30 (38%) were women and whose median age was 56 years (range, 22-65 years). Seven percent of these patients had undergone previous surgery for their disease, whereas 5% had received prior radiotherapy.  None had undergone chemotherapy. 

Following the ASA Classification of Physical Status, the distribution of patients according to operative risk for groups 1 and 2 are described in Table 1.  Because of the high prevalence of chronic disease, 93% of patients in group 1 were designated as class III or greater, in contrast to 63% of patients in group 2 (p < .001.

*Established during the preanesthetic evaluation.

 All patients underwent general anesthesia for curative resection of their upper aerodigestive tract cancers, with a mean anesthesia time of 5.0 hours for the octogenarians (median, 6.1 hours; range, 1.5-12.5 hours) and 6.8 hours for the controls (median, 8.0 hours; range, 2.3-15.5 hours) (p =.003).  The surgical procedures ranged from wide excision to total laryngopharyngectomy, and selective or modified radial neck dissections were performed on approximately 60% of patients in both groups.  However, only two octogenarian patients (4.6%) underwent microvascularized, free tissue transfer for reconstruction, whereas 17.7% of the control patients underwent free flap reconstruction of their defects (p = .08) (Table 2).  

*Some patients underwent more than one procedure

#includes partial glossectomy.

Although we currently admit patients on the day of surgery unless medically contraindicated, 44.1% elderly and 20.3% control patients were admitted 1 day preoperatively.  However, only 4 (9.3%) octogenarian patients and 7 (8.9%) controls were admitted more than 1 day prior to surgery; all these patients were classified as ASA III or IV.  No emergency surgical procedures were performed.  Forty-four percent of the octogenarian patients recovered in the surgical intensive care unit (SICU) for a mean of 1.6 days (range, 1-3 days); whereas 33% of the controls required SICU care postoperatively (mean, 2.5 days; range, 1-10 days).  There was no significant difference in the total hospitalization time between groups (p = .34).

Major postoperative complications, most of which were delayed, developed in 23.2% of the octogenarian patients (Table 3).  Minor postoperative complications, frequently urinary retention, developed in 27.7% of these patients, and 11.6% suffered from both a major and minor complication.  When genitourinary complications related to prostatic hypertrophy were eliminated from the analysis, minor complications occurred in 18.4% of the elderly cohort.  These complication rates did not differ significantly from those of the controls, in whom major complications developed in 22.6% (p = .88 and .76, respectively); 6.3%of these patients had both major and minor complications.  The majority of the complications in the control group also occurred more than 24 hours postoperatively.  There was one postoperative death in this series, which occurred in a group 1 patient on postoperative day 2 and was attributed a myocardial infarction.  The patient's preoperative ASA status was class IV.

*The majority of the complications were delayed ( >24 hours postoperatively).

#Transient ischemic attacks.

Histologic Analysis, Locoregional Recurrence, and Survival.  Pathologic review of the surgical specimens from group 1 showed that 76.7% had negative margins at the primary site and 18.6% had a positive margin; the histologic margins were not stated for 4.6%.  In addition, perineural or lymphatic/vascular invasion was seen in 16.3% and 37.2% of the patients, respectively.  Of the 27 patients who underwent neck dissections lymph node metastases were confirmed histologically in 15 and extracapsular extension or multiple levels of lymph node involvement were present in 6 (Table 40).

In comparison, 89.9% of the controls had negative margins and 7.6% had a positive margin (p = .12 versus group 1); the final margin status was not stated for 2.5%.  Furthermore, 13.9% had perineural involvement (p = .48) and 30.4% had regional metastases (p = .76).  Twelve patients (15.2%) had extracapsular spread or multiple levels of nodal involvement (p = .59) (Table 4).

In the octogenarian group, 10 patients received radiotherapy postoperatively.    Indications for radiotherapy included positive margins, perineural invasion, and extracapsular spread.  Of the 8 patients with positive margins, 4 underwent postoperative radiotherapy; 2 of these developed recurrent local disease, and 2 developed distant metastases.  The remaining 4 patients were treated with surgery alone, 2 of whom recurred both locally and regionally and 1 of whom developed distant metastases, whereas the fourth patient was without evidence of disease upon study termination. 

Overall, recurrent disease developed infrequently in the octogenarian patients.  Twenty nine patients (67.4%) had not recurred in local, regional, or distant sites at the time of study termination.  On the other hand, local recurrences alone developed in 7 patients (16.3%), regional recurrences developed in 3 ( 7.0%), and distant metastases developed in 3 patients.  Two patients recurred in more than one site. 

In the control group, 44 patients (51.3%) underwent surgery alone whereas 31 (36.1%) were treated with postoperative radiotherapy.  One patient (1.2%) underwent surgery and chemotherapy, and 3 (3.5%) were treated with all three therapeutic modalities.  Compared with group 1, the rates of local control at 1, 2, and 5 years were higher for the controls, and by 5 years postoperatively, the local control rate for group 2 was 98%, in contrast to 68% for group 1 (p < .001).  However, when regional disease was taken into account, there were no statistically significant differences between the rates of locoregional control at 1, 2 and 5 years (p = .26).  The mean follow-up time was 34.3 months for group 1 and 42.7 months for group 2. 

The median overall survival for patients in group 1 was significantly lower than that for group 2.  Five year postoperatively, the survival rate for the octogenarian patients was estimated to be 33%, as compared with 63% for the matched controls (p = .001).  when disease-specific survival was analyzed, group 1 again fared worse.  The disease-specific survival rates were lower than those of the controls at each time point,  and the 5-year survival rate was 39% for group 1 and 66% for group 2 (p = .014). 

However, when the overall survival of the octogenarian patients was compared with expected survival based on cohort life statistics derived from U. S. Bureau of the Census data (5), there was no significant difference in survival at 5 years postoperatively.

Discussion

As our population ages, head and neck surgeons will encounter an increasing number of elderly patients who need special consideration.  The risk of perioperative medical complications is significant and directly relates to the presence of concurrent illnesses (2, 6, 7).  Although chronologic age alone should not influence the treatment plan, underlying comorbid factors such as cardiovascular and respiratory disease have a profound impact on outcome and should be taken into account prior to instituting therapy.  In 1977, McGuire et al (8) reviewed the results of major head and neck oncologic surgery in 162 patients over age 70 years.  The perioperative mortality rate was 7.4%, in contrast to 1.4% in a control population of 552 patients who underwent similar procedures.  Although the elderly patients had a higher rate of medical complications, there was no significant difference in the incidence of either major or manor surgical complications between the groups.  However, this study lacked controls matched for tumor stage and histology and long-term outcomes were omitted. 

In a similar study published in 1982, Morgan et al (3) reported the perioperative morbidity and mortality rates for 810 patients over the age of 65 years who underwent major head and neck procedures and for 963 patients under 65 years of age.  They reported a mortality rate of 3.55 for the elderly patients and 0.8% for the controls.  Almost 50% of the deaths in the elderly resulted from pulmonary complications.  These patients also suffered a higher rate of nonlethal complications (32%) as compared with the control group (21%).  However, follow-up was limited to only 30 postoperative days, and the controls were not matched according to disease stage or histology.

In 1990, Barzan et al (6) retrospectively compared the operative results for 107 head and neck cancer patients over 70 years of age with those for 135 patients aged 60-69 years as well as to those for 196 patients younger than 60 years of age.  They found no difference in local disease control, postoperative complications, or survival between the groups.  However, the heterogeneous nature of the malignancies and the greater proportion of early-stage (I and II) disease in the elderly population makes interpretation of the data difficult. 

More recently, Koch et al (9) retrospectively reviewed the perioperative morbidity and mortality for 52 patients with upper aerodigestive tract SCC who were 75 years of age and older.  Although no postoperative deaths occurred, they reported  a 31% incidence of major complications, most of which developed in patients with known cardiovascular disease or diabetes mellitus.  After an average follow-up of 26 months, 16 of 40 patients available for evaluation were alive and disease-free, 13 died of their cancer, 5 died of unrelated causes, and 6 were alive with persistent disease.  The authors did not attempt to correlate age with prognosis or incidence of perioperative complications. 

Despite the high prevalence of chronic disease, the octogenarian population in the present study tolerated major head and neck procedures well, with only one postoperative death.  Compared with controls, the octogenarian group did not have a significantly different incidence of peri- or postoperative complications, and the 23.2% incidence of major complications is comparable to that reported by other authors (7, 10, 11).  However, it is possible that the similar complication rates for both groups in this study were influenced by the choice of surgical procedure.  For example, free tissue transfer was never used to reconstruct a surgical defect in the elderly patients, except when a total laryngopharyngectomy had been performed.  It is likely that less complex reconstructive techniques were performed in the older age group to minimize perioperative medical complications by reducing the length of the procedure.

Although the rates of both major and minor postoperative complications were comparable, the types of complications differed according to age.  The elderly patients were more likely to have pulmonary or cardiovascular morbidity, whereas the younger patients more frequently experienced wound-related complications.  The increased rate of medical complications in the octogenarians probably resulted from their higher frequency of preoperative medical disorders.  On the other hand, the higher incidence of wound breakdown and fistula formation in the control group may be related to the size of the surgical defects and to the substantially higher incidence of tobacco and alcohol use (data not shown).  Of the controls who had significant wound complications, 705 required flap reconstruction, and the majority also had extensive histories of both tobacco and alcohol consumption.

The local control rate and disease-free survival in the elderly patients were significantly worse than in the matched controls.  The higher incidence of positive margins and less frequent use of adjuvant therapies in the octogenarians may have played causal roles.  Although the control group was matched to the elderly group by TMN stage, 44.1% of the controls were treated with combined therapy, whereas only 23.3% of the octogenarians received adjuvant therapy.  Because of the retrospective nature of this study, the reasons for these variations in treatment are unclear but may be related to attempts to reduce morbidity through less aggressive surgical and adjuvant approaches.  Alternatively, the decreased local control and disease-free survival in the elderly also may be related to the declining immune surveillance that occurs with advancing age (12-15). 

However, when compared with actuarial survival curves for the general octogenarian population, the overall survival of the elderly study patients was not adversely affected by major surgical interventions.  By careful preoperative staging, evaluation of associated medical illnesses, and meticulous operative and postoperative management, morbidity and mortality was minimized in the elderly age group and was likely responsible for the unaltered actuarial survival.

In conclusion, major ablative surgery is well tolerated in elderly patients with upper aerodigestive tract SCC and is not associated with and increased risk of operative complications.  The outcome is influenced by the stage of disease and by associated medical illnesses, and an uncomplicated postoperative course is crucial fro achieving a successful outcome.  Therefore, surgical strategies should be individualized based on the disease extent and presence of preoperative morbid conditions to minimize operative morbidity and mortality.  In some instances, it may be necessary to reduce the length of the procedure by simplifying age alone should determine the selection of surgical or non-surgical therapies, issues regarding quality of life in these patients also must be considered prior to operative intervention. 

Acknowledgment.  The authors thank Pat Wolf, Dianna Roberts, and Terry Smith for their assistance with the statistical analyses.

REFERENCES

By: Gary L.  Clayman, DDS, MD,¹  Susan A. Eicher, MD,¹ Michael W. Sicard, MD,²  Ebrahim Razmpa, MD,³  Helmuth Goepfert, MD^1
1 Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center.
² Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, Texas.
³ Tehran University of Medical Sciences, Tehran, Iran.