Continuing Education Activity

Lung adenocarcinoma is the most common primary lung cancer seen in the United
States. It falls under the umbrella of non-small cell lung cancer (NSCLC) and has a
strong association with previous smoking. While incidence and mortality have
declined, it remains the leading cause of cancer death in the United States.
Adenocarcinoma of the lung usually evolves from the mucosal glands and represents
about 40% of all lung cancers. It is the most common subtype to be diagnosed in
people who have never smoked. Lung adenocarcinoma usually occurs in the lung
periphery, and in many cases, may be found in scars or areas of chronic inflammation.
This activity describes the pathophysiology of adenocarcinoma of the lung and
highlights the role of the interprofessional team in its management.

Objectives:

 Describe the pathophysiology of adenocarcinoma of the lung.

 Review the workup of a patient with adenocarcinoma of the lung.

 Summarize the treatment options for adenocarcinoma of the lung.

 Outline the importance of improving care coordination among

interprofessional team members to improve outcomes for patients affected by
lung adenocarcinoma.

Access free multiple choice questions on this topic.

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Introduction
Lung adenocarcinoma is the most common primary lung cancer seen in the United
States. It falls under the umbrella of non-small cell lung cancer (NSCLC) and has a
strong association with previous smoking. While incidence and mortality have
declined, it remains the leading cause of cancer death in the United States.
Adenocarcinoma of the lung usually evolves from the mucosal glands and represents
about 40% of all lung cancers. It is the most common subtype to be diagnosed in
people who have never smoked. Lung adenocarcinoma usually occurs in the lung
periphery, and in many cases, may be found in scars or areas of chronic inflammation.
[1]

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Etiology
By far, the main risk factor for any lung cancer, including adenocarcinoma, is
smoking tobacco. Due to numerous carcinogens present in tobacco smoke, primary or
secondary exposure increases risk proportional to the amount of exposure.

Other risk factors include a family history of lung cancer, or occupational exposure to
other agents such as silica, asbestos, radon, heavy metals, and diesel fumes, though
these are less prevalent. Resultant genetic mutations in the p53 gene are the most
frequent cause of tumorigenesis in NSCLC in 52% of cases.[2]

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Epidemiology
Although incidence and mortality have declined since the 1980s, in 2015 there were
221,200 new cases of lung and bronchial cancers and more than 158,000 lung cancer
deaths representing the most common cause of cancer death.

Lung cancer is also widespread globally. Despite new treatments, the 5-year survival
is less than 12% to 15%. Over the past 4 decades, there has been a marked increased
in lung adenocarcinoma in women, and this has been linked to smoking. The mean
age of diagnosis of lung adenocarcinoma is 71 years, and this particular cancer is very
rare before the age of 20. In the last 2 decades, adenocarcinoma has replaced
squamous cell cancer of the lung as the most prevalent non-small cell cancer.[3]

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Pathophysiology
Lung adenocarcinoma is classified into 4 types: adenocarcinoma in situ (AIS),
minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma, and variants of
adenocarcinoma. Of these AIS and MIA have better outcomes when resected early.
Local spread may involve spread directly to the pleura, diaphragm, pericardium, or
bronchi with advanced disease spreading to the mediastinum, great vessels, trachea,
esophagus, vertebral column, or adjacent lobe. Lymph node metastasis occurs in
peribronchial lymph nodes before moving to mediastinal or subcarinal nodes and then
the contralateral lung. Distant metastasis includes extension to a contralateral lobe,
pleural nodules, malignant pleural or pericardial effusion, or any distant site such as
the brain, bones, or liver. There is a subset of NSCLC that have mutations in
epidermal growth factor receptor (EGFR), which sensitizes them to tyrosine kinase
inhibitors, as well as anaplastic lymphoma kinase (ALK) fusion oncogene
rearrangements.[4][5]

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Histopathology
When the lung is biopsied, the histological analysis will reveal a tumor arising from
the bronchial glands. Mucus production is also quite evident. The new World Health
Organization (WHO) classification subclassifies adenocarcinomas as arising from the
following:

 Acinar

 Papillary

 Bronchoalveolar

 Mucus-secreting

Except for Stage 1 lung cancer, adenocarcinoma carries a much worse prognosis than
squamous cell cancer.

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History and Physical

Symptoms and physical signs are dependent on the stage of lung cancer. The earliest
stages are often asymptomatic, with nodules found incidentally on radiographic
images testing for other disease processes. Later stage disease may present with
nonspecific symptoms such as a cough, hemoptysis, or unintentional weight loss. If
the patient presents with a pleural effusion, he or she may have shortness of breath
with decreased breath sounds. The vast majority of patients will have a smoking
history and may have other associated diseases such as chronic obstructive pulmonary
disease (COPD) or a family history of lung cancer.

A significant number of patients with lung adenocarcinoma will present with a

locoregional spread that may include symptoms from:

 Superior vena cava obstruction

 Phrenic nerve palsy

 Horner syndrome
  Compression of brachial plexus

 Pericardial effusion

Paraneoplastic syndromes are rare with adenocarcinoma but may include:

 Cushing syndrome

 Eaton Lambert syndrome

 Hypercalcemia

 SIADH

 Hypertrophic osteoarthropathy

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Evaluation
High-risk patients like current and former heavy smokers are recommended to
undergo screening with low-dose CT scan by the US Preventative Services Task
Force.[6][7]

If a lung nodule is found, the next step depends on the and imaging characteristics of
the lung nodule. If a nodule is suspicious for lung cancer, PET/CT may be performed
followed by biopsy or surgical excision. Based upon National Comprehensive Cancer
Network Guidelines the next step is a full CT of the thorax and abdomen with contrast
(including adrenals), bronchoscopy, mediastinal lymph node evaluation, complete
blood count, and blood chemistry profile.

Brain MRI is recommended for those with Stage II, III, or IV disease to rule out
metastasis. These results are then synthesized to generate a clinical stage to guide
treatment.

If bone metastases are suspected, then a bone scan should be obtained.

PET scan is usually used to assess for recurrence of the disease.

Sputum cytology is rarely helpful as most adenocarcinomas are peripheral lesions.

Needle thoracentesis is done when an effusion is seen. It can be both diagnostic and
therapeutic.
Additionally, any patients being considered for surgical resection should undergo
pulmonary function testing to determine the feasibility of lung resection based on
predicted postoperative lung function.

If the CT scan reveals mediastinal nodes, then a mediastinoscopy or thoracoscopy is

recommended to stage the patient.

Staging of the patient is mandatory before recommending any treatment.[8][9]

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Treatment / Management
Stage I/II/IIIA

These are limited invasive tumors (NO) or limited nodal disease. The tumor is
assessed for resectability, and if operable, surgical resection is recommended with
lymph node sampling. If the patient is not an operative candidate, then definitive
radiotherapy with possible adjuvant chemotherapy may be performed if the patient
has positive nodes or is high risk. Some specific invasive tumors may be treated with
neoadjuvant chemoradiation before resection.[10][11][12]

Stage IIIB and Stage IV

These stages involve mediastinal, subcarinal, and/or contralateral nodes and

metastatic disease. These stages are considered unresectable and are treated with
chemoradiation. Some extrapulmonary sites may be treated as well for palliation.

The pathologic specimen is tested for EGFR sensitizing mutations and ALK mutation.
Those that are positive for EGFR may be treated with tyrosine kinase inhibitors, while
those exhibiting the ALK mutation may be treated with ALK inhibitors as first-line
chemotherapy. If the tumor is EGFR and ALK-negative, first-line chemotherapy is
usually a platinum-based doublet, with bevacizumab as a possible third agent.

After treatment, patients need surveillance with CT Chest every six to 12 months for
two years and annual low-dose CT. This should be done more frequently in those with
residual disease. Locoregional occurrence may be treatable. Options include external
beam radiation therapy, resection, chemotherapy, and photodynamic therapy
depending on where the lesion has recurred and the associated symptoms.[13]

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Differential Diagnosis
  Benign lung lesions

 Granulomas

 Hamartoma

 Metastatic lesion

 Pneumonia

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Surgical Oncology
Surgery is the treatment for patients with stage I to stage IIIA adenocarcinoma of the
lung. Lobectomy or a pneumonectomy are often performed.

Since these patients have a high risk of relapse, adjuvant chemotherapy is now
standard.

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Radiation Oncology
Radiation therapy is only an option for patients who are not surgical candidates.

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Medical Oncology
Because the majority of lung adenocarcinomas are incurable or advanced,
chemotherapy is often used. Despite significant advances in chemotherapy, the
survival of most patients with lung adenocarcinoma remains abysmal. Platinum-based
regimens remain the mainstay of chemotherapy.

For patients with metastatic disease, molecular targeted therapy is being offered, but
the results are not spectacular. At best the survival is increased by a few months, but
the medications can cost over $20,000 a month.

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Staging
Staging of Lung Adenocarcinoma

Occult cancer: TX N0 M0
Primary cancer not found. No lymph node or distant metastasis.

Stage 0

 T is N 0 M 0

Stage I

IA1

 T1mi N 0 M 0

 T1a N 0 M 0

IA2

 T1b N 0 M 0

IA3

 T1c N 0 M 0

IB

 T2a N 0 M 0

Stage II

IIA

 T2b N 0 M 0

IIB

 T1a/T1b/T1c N 1 M 0

 T2a/T2b N 1 M 0

 T3 N 0 M 0

Stage III

IIIA

 T1a/T2b/T2c N 2 M 0

 T2a/T2b N2 M 0

 T3 N 1 M 0

 T4 N 0/N 1 M 0
IIIB

 T1a/T1b/T1c N 3 M 0

 T2a/T2b N 3 M0

 T3 N 2 M 0

 T4 N 2 M 0

IIIC

 T3 N 3 M 0

 T4 N 3 M 0

Stage IV

IVA

 Any T/Any N M1a or M1b

IVB

 Any T/Any N M1c

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Complications
Surgery Complications

 Air leak

 Pain

 Chest deformity

 Respiratory failure and/or death

 Injury to the phrenic nerve

Chemotherapy complications

 Pancytopenia

 Infections

 Hyponatremia

 Renal failure
  Peripheral neuropathy

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Postoperative and Rehabilitation Care

Patients undergoing thoracotomy will need aggressive respiratory care including
incentive spirometry, physical therapy, and chest therapy.

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Consultations
Pulmonologist

Oncologist

Thoracic Surgeon

Intensivist

Cardiologist - for preoperative workup

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Deterrence and Patient Education

 Smoking prevention

 Tobacco control

 Worker safety and use of proper equipment to prevent inhalation of toxic

aerosols

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Pearls and Other Issues

 The treatment of lung adenocarcinoma depends on the stage. For early-stage
disease, surgery is the treatment of choice.

 For advanced disease, a combination of surgery, chemotherapy, and radiation

is used to manage pain and other complications.

 Overall, outcomes for localized disease are far superior to other forms of
treatment.
  Airway obstruction can be managed with laser and stent placement.

 Chemotherapy with targeted therapy may prolong survival, but the cost of the
medications is prohibitive.

 The majority of lung cancer patients require palliation.

 Radiation therapy is often used to manage bone and brain metastases.

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Enhancing Healthcare Team Outcomes

The majority of lung cancers are advanced at the time of diagnosis, and
consequently, the prognosis is very poor. More than 80% of patients with advanced
lung cancer are dead by 5 years. Despite all the advances, longevity has not increased
over the past 3 decades. Thus, today the emphasis is on screening for lung cancer and
prevention. Only an interprofessional team approach can help reduce the number of
lung cancers and morbidity. Nurses and pharmacists are in a prime position to educate
the public on smoking prevention. There are several antismoking aids that can be
recommended by the pharmacist. Smoking cessation has repercussions beyond just
reducing lung cancer; it can lower heart disease, stroke, and peripheral vascular
disease. Further, the public should be educated about work related to particle exposure
(eg asbestos) and take appropriate precautions. Screening for lung cancer still remains
a debatable topic. It is not recommended for everyone; as of today CT scan of the
lung can be used to screen individuals over the age of 50 who have many risk factors
for lung cancer. Whether the screening will help still remains to be seen. But it will
definitely increase the cost of healthcare.[14][15] (level III)

Evidence-Based Outcomes (level V)

 Lung cancer is deadly with overall 5-year survival of 12%.[16][17][18]

 For Stage 1 disease, 5-year survival varies from 70% to 85%.

 For locally advanced disease, the survival drops to less than 30%.

 For distant metastases, less than 5% survive five years.

持續教育活動
肺腺癌是在美國最常見的原發性肺癌。它屬於非小細胞肺癌(NSCLC)的範疇，與以前吸菸有著密切的關聯。儘管發病率和死
亡率有所下降，但它仍然是美國癌症死亡的主要原因。肺腺癌通常由黏膜腺體演變而來，約佔所有肺癌的 40%。它是最常見的
在從未吸菸的人中診斷出的亞型。肺腺癌通常發生在肺外周，並且在許多情況下，可能會在瘢痕或慢性發炎區域中發現。本活動描
述了肺腺癌的病理生理學，並突出了跨專業團隊在其管理中的作用。
目標：
• 描述肺腺癌的病理生理學。
• 審查肺腺癌患者的檢查工作。
• 概述肺腺癌的治療選項。
• 概述改善跨專業團隊成員之間的護理協調對於肺腺癌患者結果的重要性。

介紹
肺腺癌是在美國最常見的原發性肺癌。它屬於非小細胞肺癌(NSCLC)的範疇，與以前的吸菸有著密切的關聯。儘管發病率和
死亡率有所下降，但它仍然是美國癌症死亡的主要原因。肺腺癌通常由黏膜腺體演變而來，約佔所有肺癌的 40%。它是在從未
吸菸的人中診斷出的最常見的亞型。肺腺癌通常發生在肺外周，並且在許多情況下，可能會在瘢痕或慢性發炎區域中發現。

病因
遠遠來說，對於任何肺癌，包括腺癌，最主要的危險因素是吸菸煙草。由於煙草煙霧中存在大量致癌物，無論是直接或間接的接觸
都會使風險與接觸量成比例增加。
其他危險因素包括家族史中有肺癌，或職業性接觸到其他物質，如矽、石棉、氡、重金屬和柴油煙霧，儘管這些因素較不普遍。
NSCLC 中，p53 基因的遺傳突變是 52%病例中最常見的致瘤原因。

流行病學
雖然自 1980 年代以來，發病率和死亡率有所下降，但在 2015 年，肺癌和支氣管癌共新增了 221,200 例，肺癌死
亡人數超過 158,000 例，成為最常見的癌症死因。
肺癌在全球范圍內也十分普遍。儘管有了新的治療方法，但 5 年生存率仍不到 12%至 15%。在過去的 4 個十年中，女性
肺腺癌的發病率顯著增加，這與吸煙有關。肺腺癌的平均診斷年齡為 71 歲，而在 20 歲之前，這種特定的癌症非常罕見。在過
去的 20 年中，腺癌已取代鱗狀細胞肺癌成為最常見的非小細胞肺癌。

病理生理學
肺腺癌分為 4 種類型：原位腺癌（AIS）、微侵襲性腺癌（MIA）、侵襲性腺癌以及腺癌的變體。其中，AIS 和 MIA 在
早期切除時具有更好的預後。局部擴散可能涉及直接向胸膜、膈肌、心包膜或支氣管擴散，疾病進展到晚期時可能擴散到細胞間質、
大血管、氣管、食道、椎骨柱或相鄰的肺葉。淋巴結轉移首先發生在支氣管周圍淋巴結，然後轉移到縱隔或肺門下淋巴結，最後轉
移到對側肺。遠端轉移包括向對側肺葉、胸膜結節、惡性胸膜積液或心包積液，以及腦、骨骼或肝等任何遠端部位的擴散。有一部
分非小細胞肺癌的患者具有表皮生長因子受體（EGFR）突變，這使得它們對酪氨酸激酶抑制劑敏感，還有一部分患者具有類激
素增生性淋巴瘤激酶（ALK）融合致癌基因重排。
組織病理學
當對肺部進行活檢時，組織學分析將顯示腫瘤起源於支氣管腺體。黏液產生也是相當明顯的。新的世界衛生組織（WHO）分類
將腺癌細分為以下類型：
- 腺泡型
- 乳頭型
- 支氣管肺泡型
- 分泌黏液型
除了第 1 期肺癌外，腺癌的預後遠遠不如鱗狀細胞癌。

病史和體檢
症狀和體徵取決於肺癌的分期。早期階段通常無症狀，偶然在進行放射學影像檢查時發現結節，這是在檢測其他疾病過程中意外發
現的。晚期疾病可能表現為非特異性症狀，如咳嗽、咳血或不明原因的體重減輕。如果患者出現胸膜積液，他或她可能會出現呼吸
急促，呼吸音減弱。絕大多數患者都有吸煙史，可能還伴有其他相關疾病，如慢性阻塞性肺疾病（COPD）或家族史中有肺癌。

許多肺腺癌患者將出現局部轉移，可能會出現以下症狀：
- 上腔靜脈阻塞
- 膈神經麻痹
- 霍納綜合徵
- 肱神經叢受壓
- 心包積液

與腺癌相關的副癌症們很少見，但可能包括：
- 库欣综合征
- 伊顿-兰伯特综合征
- 高血钙症
- SIADH
- 骨關節肥大症

評估
美國預防服務工作小組建議，像目前或曾經重度吸菸者這樣的高危患者應接受低劑量 CT 掃描篩檢。
如果發現肺結節，下一步取決於肺結節的影像特徵。如果結節可疑是肺癌，則可以進行 PET/CT 掃描，隨後進行活檢或手術
切除。根據國家綜合癌症網絡指南，下一步是進行胸腔和腹部（包括腎上腺）對比劑全面 CT 掃描、支氣管鏡檢查、縱隔淋巴結
評估、完整血液計數和血液化學分析。
對於 II、III 或 IV 期疾病的患者，建議進行腦部 MRI 掃描以排除轉移。然後將這些結果合成，生成臨床分期以指導治療。
如果懷疑有骨轉移，則應進行骨掃描。
PET 掃描通常用於評估疾病的復發。
痰細胞學很少有幫助，因為大多數腺癌是周邊病變。
當看到滲出液時，應進行針刺胸腔穿刺。這既可以是診斷性的，也可以是治療性的。
此外，任何被考慮進行手術切除的患者都應接受肺功能測試，以確定基於預計的手術後肺功能的肺切除的可行性。
如果 CT 掃描顯示縱隔淋巴結，則建議進行縱隔鏡檢查或胸腔鏡檢查對患者進行分期。
在建議任何治療之前，對患者進行分期是強制性的。

治療/管理
I/II/IIIA 期
這些是有限的侵襲性腫瘤（NO）或有限的淋巴結疾病。對腫瘤進行可切除性評估，如果可切除，則建議進行手術切除並進行淋巴
結採樣。如果患者不適合手術，則可以進行明確的放射治療，如果患者有陽性淋巴結或高風險則可能進行輔助化療。某些特定的侵
襲性腫瘤在切除前可能會接受新輔助化療放射治療。
IIIB 期和 IV 期
這些期患者涉及縱隔、肺門下或對側淋巴結和轉移性疾病。這些期被認為是不能切除的，並且使用化療放射治療進行治療。某些額
外的肺外部位也可能進行治療以緩解症狀。
病理標本被測試以尋找 EGFR 敏感性突變和 ALK 突變。對於 EGFR 陽性的患者，可以使用酪氨酸激酶抑制劑進行治
療，而表現 ALK 突變的患者可以使用 ALK 抑制劑作為一線化療。如果腫瘤為 EGFR 和 ALK 阴性，則一線化療通
常是鉑基雙重療法，可能還可以使用貝伐珠單獨作為第三劑藥物。
治療結束後，患者需要每六至十二個月進行一次 CT 胸部監測兩年，以及每年進行一次低劑量 CT。對於有殘留疾病的患者，
這應該更頻繁地進行。局部區域的發生可能是可以治療的。選擇包括外部束射放射治療、切除手術、化療和光動力治療，具體取決
於病灶的復發部位和相關症狀。

不同的診斷結果
• 良性肺病變
• 顆粒瘤
• 畸形瘤
• 轉移性病變
• 肺炎

外科腫瘤學
手術是治療 I 期至 IIIA 期肺腺癌患者的方法。常見的手術包括肺叶切除或肺全切除。
由於這些患者有復發的高風險，輔助化療現在已成為標準。
放射腫瘤學
放射療法僅適用於不能進行手術的患者。

醫學腫瘤學
由於大多數肺腺癌無法治癒或已進展，通常使用化療。儘管化療取得了顯著進展，但大多數肺腺癌患者的生存率仍然不容樂觀。鉑
基方案仍然是化療的主要支柱。
對於有轉移性疾病的患者，分子靶向治療是一個選擇，但結果並不十分理想。最多只能增加幾個月的生存時間，但這些藥物的費用
可能每月超過 20,000 美元。

肺腺癌分期
隱性癌症：TX N0 M0
未找到原發癌。沒有淋巴結或遠端轉移。
第0期
• T是N0M0
第I期
IA1
• T1mi N 0 M 0
• T1a N 0 M 0
IA2
• T1b N 0 M 0
IA3
• T1c N 0 M 0
IB
• T2a N 0 M 0
第 II 期
IIA
• T2b N 0 M 0
IIB
• T1a/T1b/T1c N 1 M 0
• T2a/T2b N 1 M 0
• T3 N 0 M 0
第 III 期
IIIA
• T1a/T2b/T2c N 2 M 0
• T2a/T2b N2 M 0
• T3 N 1 M 0
• T4 N 0/N 1 M 0
IIIB
• T1a/T1b/T1c N 3 M 0
• T2a/T2b N 3 M0
• T3 N 2 M 0
• T4 N 2 M 0
IIIC
• T3 N 3 M 0
• T4 N 3 M 0
第 IV 期
IVA
• 任何 T/任何 N M1a 或 M1b
IVB
• 任何 T/任何 N M1c

手術併發症
• 氣漏
• 疼痛
• 胸廓變形
• 呼吸衰竭和/或死亡
• 膈神經損傷
化療併發症
• 全血球減少症
• 感染
• 低鈉血症
• 腎功能衰竭
• 周邊神經病變

手術後和康復護理
接受胸腔切開術的患者將需要積極的呼吸護理，包括鼓勵性肺活量測定、物理治療和胸部治療。
前往：
會診
肺科醫生
腫瘤學家
胸外科醫生
加護醫學專家
心臟病專家 - 進行手術前的檢查

防範和患者教育
• 防止吸煙
• 煙草管控
• 工人安全和使用適當的設備防止吸入有毒氣溶膠

要點和其他問題
• 肺腺癌的治療取決於分期。對於早期疾病，手術是首選治療方法。
• 對於晚期疾病，手術、化療和放射治療的組合用於管理疼痛和其他併發症。
• 整體而言，局部化疾病的預後遠優於其他形式的治療。
• 氣道梗阻可以通過激光和支架放置來管理。
• 使用靶向治療的化療可能會延長生存時間，但藥物的成本很高。
• 大多數肺癌患者需要緩解治療。
• 放射治療通常用於管理骨骼和腦轉移。

提高醫療團隊的成果
大多數肺癌在診斷時已處於晚期，因此預後非常差。超過 80% 的晚期肺癌患者在 5 年內去世。儘管所有進展，但在過去的
30 年中，壽命並未增加。因此，今天的重點是對肺癌進行篩查和預防。只有跨專業團隊的方法才能幫助減少肺癌的數量和發病率。
護士和藥劑師處於向公眾教育防止吸煙的最佳位置。藥劑師可以推薦幾種戒煙輔助工具。戒煙不僅僅可以減少肺癌的發生，還可以
降低心臟病、中風和周邊血管疾病的風險。此外，公眾應該接受有關與粒子暴露相關的工作（例如石棉）並採取適當的預防措施的
教育。肺癌篩查仍然是一個有爭議的話題。不建議對每個人進行篩查；截至目前，可以使用肺部 CT 掃描對年齡超過 50 歲且
有許多肺癌風險因素的個人進行篩查。篩查是否有助於治療仍有待觀察。但它肯定會增加醫療保健的成本。
從證據的角度來看（第五級）
• 肺癌是致命的，整體 5 年存活率為 12%。
• 對於第 1 期疾病，5 年存活率從 70% 到 85% 不等。
• 對於局部晚期疾病，存活率下降至不到 30%。
• 對於遠端轉移，不到 5% 的患者能夠存活五年。