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Lung cancer

Lung Cancer

Epidemiology:

Lung cancer ranks among the most significant malignancies globally, with an estimated 2.2 million new cases reported, accounting for approximately 11.4% of all cancers.1 In the United States, approximately 239,000 new lung cancer cases occur annually, coupled with around 132,000 related deaths, underscoring its considerable public health burden.1Despite ongoing advances in treatment, lung cancer remains a leading cause of cancer-related mortality worldwide, reflecting its high fatality rate and the complex interplay of risk factors such as smoking and environmental exposures.2Spontaneous remission (SR) in lung cancer is exceptionally rare, documented in less than 1% of cases; this rarity complicates accurate assessments of true incidence, as milder forms of remission may go unnoticed or unreported.3

Clinical Characteristics:

To date, 43 well-documented cases of SR involving primary or metastatic lung cancer have been reported in the literature between 1954 and 2025. Reported patient ages ranged from 34 to 90 years, with the majority occurring in the sixth to eighth decades of life. A distinct male predominance (approximately 3:1) was evident, suggesting a greater SR incidence among men. Overall, SR was most frequently observed in older individuals, often associated with advanced or recurrent disease and occasionally following local immune stimulation such as infection, biopsy, or radiation exposure. See table 1 below for further information.

Histological Characteristics:

Patients who experienced SR of lung cancer commonly presented with cough, hemoptysis, chest pain, dyspnea, or weight loss. Diagnosis was typically established through imaging studies and confirmed by histopathological examination of bronchial or lung tissue. In most cases, the disease was locally advanced or metastatic, frequently involving mediastinal lymph nodes, bone, liver, or other distant sites. Remission was generally verified by radiologic or histologic assessment, often revealing resolution of the tumor mass or its replacement by fibrotic tissue. Nearly all reported SR cases were associated with prolonged survival or sustained remission, occasionally persisting for several years, markedly exceeding the expected prognosis for lung cancer.

Proposed Contributing Mechanisms:

Multiple mechanisms have been suggested to explain spontaneous remission in lung cancer. The most commonly cited involve activation of immune responses directed against tumor cells, often following infection, biopsy, radiation exposure, or other localized inflammatory events. These stimuli may enhance tumor antigen recognition and lead to cytotoxic immune activity capable of inducing tumor regression. Vascular disturbances such as thrombosis or ischemic necrosis, as well as drug-induced tumor infarction, have also been implicated in a subset of cases. In addition, psychological factors, hormonal influences, and metabolic or systemic stressors have been proposed to contribute indirectly to immune modulation. Overall, the evidence suggests that spontaneous remission in lung cancer likely arises from a complex interplay of immune activation and tumor microenvironmental changes that collectively disrupt tumor viability and growth.

Site and Extent of Remission:

Most reported SR events in lung cancer represented complete regressions, with only a few showing partial or site-specific responses. In several cases, both primary and metastatic lesions regressed, most commonly in the lung, lymph nodes, bone, or liver. The duration of follow-up ranged from weeks to more than a decade, with many patients remaining disease-free for extended periods. Unlike several other tumor types, SR in lung cancer has occasionally resulted in durable remission and long-term survival.

Table 1: Lung Cancer SR Cases and Clinical Characteristics

Author–year

Age/sex

Primary site

Remission site

Proposed mechanisms

Follow-up

Blades et al., 19544

59/M

Right lung

Right lung

Not reported

5 years

Bell et al., 19645

37/M

Left lung

Left lung

Fever-induced immune response

5 years

Margolis et al., 19676

58/M

Right lung

Right lung

Infection-induced immune response

12 years

Emerson et al., 19687

63/M

Right lung (hilar region)

Right lung

Not reported

12 years

Bell, 19708

Not reported

Left lung

Left lung

Immune response, Radiation effect

10 years

Takita, 19709

Not reported

Lung

Lung

Infection-induced immune response

Not reported

Sutton et al., 197010

64/F

Right lung

Right lung, Humerus

Radiation-induced immune response

3 months

Smith, 197111

59/M

Left lung

Left atrial wall

Infection-related Immune response

Not reported

Smith, 197111

56/M

Left lung

Left atrial wall

Infection-related Immune response

Not reported

Smith, 197111

43/M

Left lung

Left atrial wall

Infection-related Immune response

Not reported

Greentree, 197312

59/M

Right lung

Not reported

Not reported

15 years

Luosto et al., 197413

42/F

Right lung (upper lobe)

Right lung

Circulatory disturbance, Post-pregnancy changes

7 years

Baker, 197614

Not reported

Lung

Lung

Not reported

Not reported

Meares, 198015

34/M

Lung

Neck (metastasis), Lung

Meditation-related immune response

7 months

Lowy et al., 198616

55/M

Right lung

Scalene lymph nodes

Not reported

19 years

Sperduto et al., 198817

61/M

Left lung (hilum)

Left adrenal gland, Left hilum

Not reported

Not reported

Ooi et al., 201818

77/M

Right lung

Right lung, Lymph nodes

Biopsy-induced immune response

2 years

Ariza-Prota et al., 201819

8/M

Right lung

Cervical lymph nodes, Skin, Chest wall

Not reported

3 months

Esplin et al., 201820

57/M

Left lung

Left lung

Not reported

3 months

Iwayama et al., 201821

71/F

Lung

Lung

Drug-induced tumor infarction

Not reported

Tsunezuka et al., 201822

38/F

Lung

Lung

Vascular thrombosis

Not reported

Matsui et al., 201823

56/F

Lung

Lung

Biopsy-induced immune activation

6 weeks

Yoon et al., 201924

74/F

Left lung

Left lung

Immune-mediated response

1 year

Ugajin et al., 201925

82/M

Lung

Lung, Lymph nodes

Immune activation, hormonal effect

18 months

Hashimoto et al., 202026

72/M

Lung

Liver

Methotrexate withdrawal, Immune response

5 months

Shatola et al., 202027

73/M

Lung

Lung, Lymph nodes

BCG-induced immune response

3 months

Song et al., 202128

80/M

Left lung

Left lung, Mediastinal lymph nodes, Hilum

Left lung, Mediastinal lymph nodes, Hilum

52 weeks

Kim et al., 202129

60/M

Lung

Lung

Infection-induced immune response

3 weeks

Sekine et al., 202130

81/M

Lung

Lung, Lymph nodes

Biopsy-induced immune activation

2 months

Shibata et al., 202131

83/F

Lung

Lung, Lymph nodes

Not reported

7 years

Yamamoto et al., 202232

69/M

Right lung

Right lung

Not reported

Not reported

Yamamoto et al., 202232

77/M

Right lung

Thoracic vertebra, Right lung

Not reported

Not reported

Iwasaki et al., 202233

74/M

Right lung

Right lung

Not reported

4 months

Schiavon et al., 202234

74/M

Lung

Lung

Infection-induced immune response

1 month

Ahmad et al., 202235

59/M

Lung

Lung, Lymph nodes

Immune activation post-biopsy

4 months

Goto et al., 202336

78/F

Left lung

Left lung

Biopsy-induced immune response

Not reported

Sasahara et al., 202337

60/M

Lung

Lung

Biopsy-induced immune activation

20 months

Tatsumoto et al., 202438

80/M

Right lung

Rib, Mediastinal lymph node

Immune activation

4 months

Koike et al., 202439

76/M

Lung

Lung, Lymph nodes

Immune stimulation

4 months

Hong et al., 202440

71/M

Lung

Lung, Lymph nodes

Infection-induced immune response

1 year

Kim et al., 202541

56/M

Lung

Lung, Lymph nodes

Not reported

2 years

Sawamura et al., 197542

43/M

2 months

Sewpaul, 201443

35/F

Pelvic - right uterosacral region

None reported

9 years

Papac, 199044

62/F

Left lung

None reported

8 years free of metastatic disease

Horstmann et al., 197745

30/F

Lungs

Lungs

Asymptomatic postpartum

Horstmann et al., 197745

30/F

Pulmonary nodules

Hormonal dependence

Gautam, 196946

53/M

Left hilum

None reported

Normal roentgenograms and bronchoscopies

Tan-Garcia, 202447

39 months/M

Fetal lung

Intrathoracic mass

Genomic breakpoint in A2M inactivates ALK kinase

Gradual reduction in mass size

Pokhrel, 202248

64/M

Prostate

Lungs

Abscopal effect

14 months

Wilson, 202549

67/M

Lung

Lung

Immune trigger

6 months

Wilson, 202549

67/M

Lung

Lung

Better prognosis and potential for regression

6 months

Grillet et al., 198450

26/M

Lung lesions

Since 1980, lesions are only barely visible

Depierre et al., 198451

57/M

Rise in NK cells

4 years

Levine et al., 197052

Larynx

No evidence of tumor at 2 years or at autopsy 12 years later

Khattar et al., 197553

Newborn/F

Alive at 6 years

Lee et al., 198254

20 months/M

Asymptomatic at age 20

Johnson, 195155

43/F

Pulmonary metastases

Benett, 196856

24/F

Lung

Normal chest x-rays since July 1962

Hossri, 197657

Respiratory system

Acupuncture and hypnosis

Rosenow et al., 197158

28/M

Lung

Lennard & Lennard et al., 625359

68/F

Skin

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