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Kidney cancer

Kidney Cancer

Epidemiology:

Kidney cancer, predominantly renal cell carcinoma (RCC), represents a significant public health concern, with approximately 79,000 new cases diagnosed annually in the United States alone 1. Despite healthcare advancements, the disease's natural history is often marked by unpredictable trajectories, including occasional spontaneous remissions (SR), which are exceedingly rare, reported in less than 1% of RCC cases. SR occurrences in RCC are typically noted when there is a notable regression of metastatic lesions or complete tumor shrinkage without treatment, complicating the estimation of their prevalence and obscuring clinical patterns due to underreporting of less dramatic cases 2. Furthermore, the phenomenon suggests potential interactions between immune mechanisms and tumor biology, prompted by factors such as inflammatory responses or surgical interventions, which may catalyze spontaneous regression, although the underlying mechanisms remain inadequately understood 3.

Clinical Characteristics:

To date, there have been over 60 reported cases of SR of either primary or metastatic renal cell carcinoma (RCC). Several clinical patterns emerge from the documented cases. The age at the time of regression ranges from 37 to 86 years, with a peak incidence between 55 and 70 years. Males constitute the majority of cases, reflecting a marked male predominance consistent with the general epidemiology of RCC. Reported instances involve both primary renal tumors and metastatic sites, most frequently within the lungs, though regressions have also been observed in the bone, liver, adrenal gland, brain, and lymph nodes. See Table 1 below for detailed case information.

Histological Characteristics:

Among the reported cases, the histopathology of the tumors was predominantly clear cell renal cell carcinoma, although other subtypes were occasionally described in later reports. Cases involving non-renal primary malignancies or metastatic lesions of non-renal origin were excluded from this compilation to maintain diagnostic specificity. Only histologically confirmed renal carcinomas demonstrating partial or complete spontaneous regression were considered in the data collection.

Proposed Contributing Mechanisms:

Multiple mechanisms have been proposed to explain spontaneous regression in renal cell carcinoma (RCC). The most frequently reported involve immune activation following nephrectomy or tumor removal, suggesting that the elimination of the primary lesion may restore or enhance systemic immune surveillance. Other hypothesized contributors include hormonal and endocrine modulation, infection-induced immune stimulation, ischemic necrosis, and tumor-specific immunologic responses. More recent cases have linked regression to drug withdrawal effects (such as sunitinib or methotrexate cessation) and immune activation following viral infections, including SARS-CoV-2. Collectively, these observations indicate that spontaneous regression in RCC likely arises from multifactorial biological pathways integrating immune, vascular, and metabolic mechanisms.

Site and Extent of Remission:

The kidney was the primary site in nearly all reported cases of spontaneous regression of renal cell carcinoma (RCC), with regression most frequently observed in metastatic lesions rather than the primary tumor itself. The lungs represented the most common site of remission, followed by the bone, liver, adrenal gland, brain, and lymph nodes. A smaller subset of cases documented regression at the primary renal tumor site, often attributed to ischemic necrosis or thrombosis. In several modern reports, regression followed immune activation after nephrectomy, drug withdrawal, or SARS-CoV-2–related immune responses. The follow-up periods among these cases ranged from a few months to over 20 years, with many patients maintaining prolonged remission or clinical stability. Unlike most solid malignancies, spontaneous regression in RCC has occasionally been durable and complete, underscoring its unique biological behavior.

Table 1: Kidney Cancer SR Cases and Clinical Characteristics

Author–year

Age/sex

Primary site

Remission site

Proposed mechanisms

Follow-up

Bumpus, 19284

59/M

Kidney

Lungs

Not reported

5 years

Rae, 19355

61/F

Kidney

Not reported

Necrosis and calcification

Not reported

Mann, 19486

62/M

Kidney

Lungs

Not reported

4 years

Bartley et al., 19507

Not reported

Kidney

Not reported

Endocrine factors, Tuberculosis association

Not reported

Bartley et al., 19507

73/M

Kidney

Not reported

Not reported

Not reported

Bartley et al., 19507

58/F

Kidney

Not reported

Not reported

Not reported

Arcomano et al., 19588

37/M

Kidney

Lungs

Not reported

3 years

Hallahan, 19599

75/M

Kidney

Lungs

Not reported

2 years 9 months

Kessel, 195910

65/M

Kidney

Lungs

Biological tumor properties

7 months

Jenkins, 195911

57/M

Kidney

Lungs

Not reported

8 years

Ljunggren et al., 195912

Not reported/M

Kidney

Frontal lobe of brain

Antibody reaction

Not reported

Nicholls et al., 196013

55/M

Kidney

Lungs

Nephrectomy related

2.5 years

Buehler et al., 196014

59/M

Kidney

Lungs

Post-nephrectomy response

14 months

Buehler et al., 196014

59/F

Kidney

Lungs

Post-nephrectomy response

22 months

Samellas et al., 1961115

43/M

Kidney

Lungs

Not reported

2 years

Bartley et al., 196216

73/M

Kidney

Not reported

Not reported

Not reported

Bartley et al., 196216

58/F

Kidney

Not reported

Not reported

Not reported

Prentiss et al., 196217

63/F

Kidney

Lungs

Removal of primary tumor

15 years

Miller et al., 196218

57/M

Kidney

Lungs

Not reported

27 months

Zak, 195719

86/F

Kidney

Not reported

Not reported

Not reported

Zak, 195719

71/F

Kidney

Not reported

Not reported

Not reported

Sakula, 196320

61/M

Kidney

Lungs

Not reported

10 weeks

Andrews, 196521

49/F

Kidney

Lungs

Post-nephrectomy response

3 years

Schapira et al., 196722

82/M

Kidney

Lungs

Not reported

20 years

Goodwin, 196823

Not reported

Kidney

Not reported

Immunologic response, Hormonal control

Not reported

Mathias, 197124

59/F

Kidney

Lungs

Post-nephrectomy response

Not reported

Meinders, 197125

68/M

Kidney

Lungs

Not reported

9 months

Garfield et al., 197226

61/M

Kidney

Lungs

Hormonal and immunologic factors

18 weeks

Holland, 197327

Not reported

Kidney

Lungs

Tumor-specific immunologic response

Not reported

Silber et al., 197528

53/M

Kidney

Lungs

Not reported

1 year

Schirmer, 197629

Not reported

Genitourinary system

Not reported

Post-nephrectomy response

Not reported

Doolittle, 197630

49/M

Kidney

Bone

Not reported

6 months

Freed et al., 197731

49/F

Kidney

Bone

Not reported

21 years

Gutierrez et al., 198032

72/F

Kidney

Lungs

Spontaneous reversion

Not reported

Viville, 198133

52/F

Kidney

Lungs

Hormonal factors, Immunological factors

Not reported

Busato et al., 198134

45/M

Kidney

Lungs

Immunologic alterations, Hormonal modifications

Not reported

Gelfand et al., 198135

53/M

Kidney

Lungs

Not reported

2 years

Snow et al., 198236

64/M

Kidney

Lungs

Not reported

Not reported

Nakano et al., 198437

57/M

Kidney

Lungs

Not reported

8 years

Mage et al., 198638

55/M

Kidney

Lungs

Tumorous emboli

3 years

Mage et al., 198638

58/M

Kidney

Right lung

Not reported

16 months

Kirk , 198739

Not reported

Kidney

Lungs

Not reported

2.5 years

Chapple et al., 198740

57/M

Kidney

Lungs

Not reported

Not reported

Ritchie et al., 198841

52/M

Kidney

Liver

Not reported

9 months

Iwaki et al., 201842

77/F

Kidney

Lungs

Methotrexate discontinuation

8 months

Srivastava et al., 201843

66/F

Kidney

Not reported

Tumor antigen release

Not reported

Okazaki et al., 202044

57/F

Kidney

Lungs

Immune response after nephrectomy

6 months

Muraoka et al., 202045

59/M

Kidney

Lungs, Mediastinal lymph node

Immune activation after tumor removal

4 months

Buchler et al., 202146

71/M

Kidney

Lungs, Mediastinal lymph node

SARS-CoV-2–induced immune response

1 year

Buchler et al., 202146

58/M

Kidney

Lungs

SARS-CoV-2–induced immune response

6 months

McGillivray et al., 202347

57/M

Kidney

Lungs

Not reported

3 months

Mullasseril et al., 202448

52/M

Kidney

Paraspinal muscles, Lymph nodes

Immune response triggered

57 days

Kara, 200049

38/F

Kidney/Adrenal glands

Surrenal haematoma

6 months

Ohta et al., 200950

70/F

Right subclavian artery

Balloon angioplasty

Sanchez-Orightiz et al., 200351

56/M

Kidney

Lung metastases

Immunological response

Complete disappearance of pulmonary metastases

Lilienthal, 191352

58/F

Right breast

None

Yang, 202153

55/M

Kidney

Adrenal gland

Antiandrogen withdrawal syndrome

22 months

Freih-Fraih, 202254

79/F

Kidney

Kidney

Surgical procedure

Schaschula, 202455

60/M

Kidney

Right renal mass

Tumor regression due to compromised blood supply

11 months

Ito, 202156

52/M

Kidney

None reported

Teng et al., 196357

62/M

Bones

Complete regression at 16 months

Grabstald, 196458

57/M

Chest

Normal findings at 5 years

Wagle, 197259

57/M

Lower lung fields

Remission persisted to present

Barré et al., 198660

Immune response from bacterial infection

Alive at 5 years

Barré et al., 198660

49/M

3 weeks

Stapleton et al., 198161

2/M

Kidneys

Alive and healthy at 2 years

Labrune et al., 198762

Infants

Disappearing within several months

References:

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