RESULTS

Incidence of lung cancer

According to the SEER database, 1,148,341 patients developed lung cancer from 1973 to 2015, including 646,662 males and 501,679 females. Of these, white patients comprised the majority (n=960,808), followed by black patients (n=122,079), and then other racial patients (n=64,010), and unknown racial patients (n=1,444). A high incidence rate of lung cancer was observed with 59.0/100,000 person-years on average over the past 43 years. In 1973, the incidence of lung cancer was 47.5/100,000 person-years. The overall incidence of lung cancer significantly increased from 1973 to 1991, and reached a peak in 1992 (65.9/100,000 person-years). The incidence then decreased from 1991 to 2015, which was mainly due to a decrease in incidence in male patients. In 2015, the incidence dropped to 48.9/100,000 person-years (Figure 1A).


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Male patients showed a decreasing trend, while female patients showed an increasing trend in overall incidence in the past decades. The incidence rate in male patients increased from 1973 (83.5/100,000 person-years) to 1984 (97.9/100,000 person-years), and then gradually decreased to a historical low level of 55.3/100,000 person-years in 2015. However, the incidence in female patients gradually increased from 20.2/100,000 person-years in 1973 to 51.3/100,000 person-years in 2007. The incidence subsequently decreased slowly and was 44.2/100,000 person-years in 2015. In general, the incidence in male patients was higher than that in female patients, but this gap has gradually diminished in recent years (Figure 1B). There was a significant change in the average age of patients with lung cancer from 1973 (64.1 years) to 2015 (70.3 years). With regard to racial groups, the incidence rate in black patients was the highest among all racial groups during the same time period (white vs black vs others =61.94 vs 78.99 vs 42.39/100,000 person-years on average). Black patients showed an increased incidence from 1973 to 1985, and then a decrease from 1985 to 2015. In white patients, there was an increase in incidence from 1973 to 1991, followed by a significant decrease from 1991 to 2015. The other racial groups showed the lowest incidence rates, which remained relatively stable from 1973 to 2015 (Figure 1C).

Lung cancer stage was divided into the following four categories: localized, regional, distant, and unstaged (Figure 1D). The average percentage of localized, regional, distant, and unstaged lung cancers was 18.8%, 23.7%, 47.7%, and 10.0%, respectively. Localized stage lung cancer showed an increasing trend, rising from 16.6% in 1988 to 23.6% in 2015. The percentage of regional stage lung cancer showed a slight decreasing trend (24.6% in 1988 to 21.7% in 2015). The percentage of distant stage lung cancer far exceeded that of the other two stages, and remained at a high level with a general increasing trend (45.2% in 1988 to 48.7% in 2015). For unstaged lung cancer, the percentage had been on a decline from 1988 (14.2%) to 2015 (6.1%).

The histopathological types of lung cancer mainly consisted of ADC, SCC, LCC, and SCLC (Figure 2). The average incidence rates of ADC, SCC, LCC, and SCLC were 17.9, 13.3, 3.1, and 6.0/100,000 person-years, respectively. Overall, ADC showed an increasing trend in incidence from 1973 (8.9/100,000 person-years) to 2015 (20.3/100,000 person-years), while SCC showed a decreasing trend from 1973 (13.3/100,000 person-years) to 2015 (9.8/100,000 person-years). The incidence rate of SCC significantly increased from 1973 and reached a peak in 1984, and then decreased from 1984 to 2005. Following a stable period, SCC showed a decreasing trend in incidence from 2011 to 2015. In general, the incidence rate of ADC increased from 1973 to 1992. After a nonsignificant decrease, the incidence increased again from 2003 to 2015. In 1985, the incidence rate of ADC surpassed that of SCC for the first time and this disparity continuously increased. The incidence rate of LCC was relatively low, and increased initially (1973 to 1987) and then decreased (1987–2015). The incidence of SCLC was higher than that of LCC, and also showed periods of increased and decreased incidence. The incidence of lung cancer in male patients was higher than that in females for all four histopathological types, but the gap narrowed with time (Figure 3A–D). Notably, in females, the incidence of ADC significantly increased from 5.4/100,000 person-years in 1973 to 19.5/100,000 person-years in 2015, whereas the incidence of SCC in male patients significantly decreased from 25.5/100,000 person-years in 1973 to 13.3/100,000 person-years in 2015.

Treatment of lung cancer

The main treatments for lung cancer include surgery, chemotherapy, and radiotherapy. In the present study, although the surgical rate showed slight fluctuations over time, it remained relatively stable at about 25%. The radiotherapy rate experienced a general downward trend, but showed an increasing trend from 2007 (35.3%) to 2015 (38.8%). However, treatment with chemotherapy rose over the past decades, increasing from 14.9% in 1973 to 39.2% in 2015 (Figure 4).

The present study revealed that the surgical rates for NSCLC were much higher than those for SCLC (Figure 5A). From 1973 to 2015, the highest average surgical rate was seen in ADC patients (36.6%), followed by SCC (31.2%), LCC (26.4%), and SCLC patients (5.9%). The surgical rates for ADC, SCC, and SCLC decreased over time, but the rate for LCC significantly increased from the late 1980s. As shown in Figure 5B, most patients with localized stage lung cancer underwent surgical treatment (an average of 61.6%). However, the surgical rate significantly decreased from 1988 to 2015. The average surgical rate for regional stage lung cancer was 38.2%, ranking second, while only 5.1% of patients with distant stage lung cancer underwent surgery, and this rate declined from 1988 to 2015. For unstaged tumor, the average surgical rate was 3.6%, and showed a decreased trend from 1973 to 2015.

All four histopathological types of lung cancer showed an increasing trend in treatment with chemotherapy from 1973 to 2015 (Figure 5C). In 1973, the rates of chemotherapy for ADC, SCC, LCC, and SCLC were 19.6%, 11.7%, 17.1%, and 24.2%, respectively. Following a continuous increase in chemotherapy, the rates of chemotherapy in these four histopathological types rose to 43.0%, 39.2%, 50.2%, and 67.8%, respectively. Notably, on average 65.4% of SCLC patients received chemotherapy, which was much higher than that in the other three histopathological types. However, the rate of chemotherapy in SCLC patients decreased from 1987 to 2015. For regional and distant stage lung cancer, the rate of chemotherapy increased from 1988 to 2015. In 2015, the rates of chemotherapy for regional and distant stage lung cancer were 53.3% and 51.2%, respectively, while on average, only 12.4% of patients with localized stage lung cancer were treated with chemotherapy (Figure 5D). The treatment with radiotherapy for NSCLC experienced a significantly decreasing trend from 1980s to 2006. Since then, NSCLC have an increasing trend in radiotherapy rate. But for SCLC, the radiotherapy rate increased initially, and then rapidly went to the bottom in 1989 (38.7%). Later, it increased gradually, reaching 44.5% in 2015 (Figure 5E). Regional and distant stage lung cancer had higher radiotherapy rate than localized stage. The radiotherapy rate of both regional and distant stage lung cancer experienced a decreasing trend from 1988 to the mid 2000s, and then remained stable (Figure 5F).

Long-term survival of lung cancer patients

In 1973, the 5-year relative survival rate of all patients with lung cancer was only 10.7% (Figure 6A). Although the survival rate has increased over the past four decades, it is still poor (<21.0%). In 2010, the 5-year relative survival rate increased to 19.8%.

Female patients had a better survival rate than male patients at all time points (Figure 6B). The average survival rate of male patients was 13.0%, while the rate in female patients was 17.7%. All racial groups showed an increasing trend in survival rate over the years. Black patients had the lowest survival rate at all time points, while white patients and other racial patients had better survival rates (Figure 6C). In general, aged lung cancer patients had a poorer survival rate than younger patients (Figure 6D). Notably, all age groups showed a marked increase in survival rate, especially patients aged 15–44 years.

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