2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Table 1. Surgical Management and Outcomes in Elderly
Patients with Early Stage NSCLC
More recent studies provide a current idea of the risks and
outcomes for older patients with early stage NSCLC. A
nested case-control study in France between January 2004
and December 2008 matched nearly 2,000 patients age 70 or
older with stage I/II NSCLC with matched controls younger
than age 70 in order to compare surgical treatment and
postoperative outcomes. 9 These results are outlined in Table
1. Although the frequency of radical lymph-node dissection
was more common in the younger patient, there was otherwise
no significant difference in the type of resection between
younger and older patients. The frequency of
lobectomy was 77% in the younger patient and 79% in the
older patients, with pneumonectomy in 11% of the younger
patients and 8% in the older patients. Sublobar resections
occurred in only 7% of the patients younger than age 70 and
6% over the age of 70. Postoperative mortality was higher in
the older patient with a 30-day mortality of 3.6% compared
with 2.2% in the younger patients (p � 0.01). For the older
population, perhaps an even more important endpoint is the
90-day mortality. This endpoint was 4.7% in those patients
older than age 70 compared with 2.5% in the population
younger than age 70 (p � 0.0002). This result in particular
shows the vulnerability of this population after thoracic
surgery. However, the relatively low mortality in this age
group across a wide number of institutions in France reassures
us that patients appropriately selected for surgery can
have similar outcomes.
Improved outcomes with higher surgery rates for older
patients with early-stage NSCLC have been recently reported
from a national cohort study of over 17,000 Medicare
KEY POINTS
� age 70 � age 70
n � 1,969 n � 1,969
Lobectomy 77% 79% NS
Pneumonectomy 11% 8% NS
30 d mortality 2.2% 3.6% p � 0.01
90 d mortality 2.5% 4.7% p � 0.0002
● The majority of lung cancer occurs in the older
population.
● Advances in staging, surgery, and perioperative management
have increased the number of older patients
who are candidates for surgical resection for earlystage
lung cancer.
● Although the elderly population is clinically underrepresented
in clinical trials, the data suggest that
older, fit patients may have similar benefit with
adjuvant chemotherapy than younger patients with
a modest increase in toxicities.
● Observational databases suggest that these benefits
extend to the patients outside of clinical trials. In the
United States, carboplatin is commonly substituted
for cisplatin in the older patient population and
benefits may be comparable within the limits of this
data.
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patients with stage I or II NSCLC, identified through the
SEER database between 2001 and 2005. 10 In this study,
areas of high and low rates of curative surgery for earlystage
lung cancer were compared in an attempt to determine
the effectiveness of surgery in older and sicker patients. In
the low surgery areas, less than 63% of patients underwent
surgery compared with greater than 79% in high surgery
areas. Those high surgery areas also operated on more
patients with advanced age and patients with chronic obstructive
pulmonary disease. Despite this, the overall 1-year
mortality was 18% in the high surgery area compared with
22.8% in the low surgery area (adjusted odds ratio [OR] 0.89;
95% confidence interval [CI] 0.86–0.93). In addition, the
1-year lung cancer specific mortality was lower in the high
surgery area at 12% compared with 16.9% for the low
surgery area (OR 0.86; 95% CI 0.82–0.91). The training
effect and expertise of the areas with higher rates of surgery
was associated with older and sicker patients undergoing
resection with improved survival. This speaks strongly to
the need for identifying broader expertise and centers of
excellence for surgical intervention in older patients, both in
the academic and community settings.
Adjuvant Chemotherapy Clinical Trials
JEFFREY CRAWFORD
The 5-year survival rate for surgical resection alone in
NSCLC is approximately 55% to 65% for patients with stage
I disease, 40% to 55% for patients with stage II, and 20% to
25% for stage III. Based on the Mountain staging system,
which has served as the basis for the majority of adjuvant
chemotherapy trial results currently available, 11 the Lung
Adjuvant Cisplatin Evaluation (LACE) pooled analysis has
reported survival improvement following surgical resection
with the use of adjuvant chemotherapy between 4% and
15%. 12 Among these trials, JBR.10 was a study conducted by
the National Cancer Institute of Canada, comparing cisplatin
and vinorelbine with observation. A subset analysis has
been reported for the patients older than age 65 in this
trial. 13 Three hundred twenty-seven patients age 65 or
younger were compared to 155 patients older than age 65.
The baseline demographics were similar for the two groups,
with the exception of histology with 58% of younger patients
having adenocarcinoma compared with 43% of the older
patients. Squamous cell cancer was seen in 32% of the
younger patients and 49% of the older patients (p � 0.001).
Performance status 0 was also more frequent in the younger
population—53% compared with 41% (p � 0.01). Chemotherapy
significantly prolonged overall survival in the older
population with a hazard ratio of 0.61 (95% CI, 0.38–0.98).
This benefit was quite similar to the effect seen for the
overall study population. Differences were seen in the mean
dose intensity of vinorelbine and cisplatin, with the elderly
patients receiving fewer doses of both agents. Fewer elderly
patients completed treatment and more patients refused
treatment. There were no significant differences in toxicities,
hospitalizations, or treatment-related deaths by age
group. There was a higher mortality rate from nonmalignant
causes in the older population—21.1% compared with
11.9% in the younger population, although this did not reach
statistical significance. The authors concluded that, despite
the fact that the older population received less chemotherapy
overall, the improvement in survival of adjuvant vinorelbine
and cisplatin was comparable to the result seen in
the younger population and also had acceptable toxicity.