Kidney cancer - Spontaneous Remission Database

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
Viville, 1981³²	52/F	Kidney	Lungs	Hormonal factors, Immunological factors	Not reported
Busato et al., 1981³³	45/M	Kidney	Lungs	Immunologic alterations, Hormonal modifications	Not reported
Gelfand et al., 1981³⁴	53/M	Kidney	Lungs	Not reported	2 years
Snow et al., 1982³⁵	64/M	Kidney	Lungs	Not reported	Not reported
Nakano et al., 1984³⁶	57/M	Kidney	Lungs	Not reported	8 years
Mage et al., 1986³⁷	55/M	Kidney	Lungs	Tumorous emboli	3 years
Mage et al., 1986³⁷	58/M	Kidney	Right lung	Not reported	16 months
Kirk , 1987³⁸	Not reported	Kidney	Lungs	Not reported	2.5 years
Chapple et al., 1987³⁹	57/M	Kidney	Lungs	Not reported	Not reported
Ritchie et al., 1988⁴⁰	52/M	Kidney	Liver	Not reported	9 months
Iwaki et al., 2018⁴¹	77/F	Kidney	Lungs	Methotrexate discontinuation	8 months
Srivastava et al., 2018⁴²	66/F	Kidney	Not reported	Tumor antigen release	Not reported
Okazaki et al., 2020⁴³	57/F	Kidney	Lungs	Immune response after nephrectomy	6 months
Muraoka et al., 2020⁴⁴	59/M	Kidney	Lungs, Mediastinal lymph node	Immune activation after tumor removal	4 months
Buchler et al., 2021⁴⁵	71/M	Kidney	Lungs, Mediastinal lymph node	SARS-CoV-2–induced immune response	1 year
Buchler et al., 2021⁴⁵	58/M	Kidney	Lungs	SARS-CoV-2–induced immune response	6 months
McGillivray et al., 2023⁴⁶	57/M	Kidney	Lungs	Not reported	3 months
Mullasseril et al., 2024⁴⁷	52/M	Kidney	Paraspinal muscles, Lymph nodes	Immune response triggered	57 days
Mcdermott & Khettry et al., 1994⁴⁸	23 -year-old who had been in excellent general health until February 1973, she had not taken birth con- trol pills or any other hormonal medication, and there was absolutely no significant medical or dietary adjunct or variant	liver + both liver lobes mets	She was last seen in the office in May of 1993, 20years after resection of a primary clear cell carcinoma of the liver with diffuse metastatic nodules of the microscopically proven tumour throughout both lobes of the liver. Recent CAT scan and ultrasound study of the liver have been carried out and show no evidence of residual or metastatic disease, except for mild diabetes, which is under control, she remains in excellent health in every respect.	either regression or differentiation and maturation into normal hepatocytes.	She was last seen in the office in May of 1993, 20years after resection of a primary clear cell carcinoma of the liver with diffuse metastatic nodules of the microscopically proven tumour throughout both lobes of the liver. Recent CAT scan and ultrasound study of the liver have been carried out and show no evidence of residual or metastatic disease, except for mild diabetes, which is under control, she remains in excellent health in every respect.
Ohta et al., 2009⁴⁹	70 years old woman, History of end-stage renal disease secondary to anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Hemodialysis for 5 years. The arteriovenous (AV) shunt in her left forearm had become stenotic twice	Right subclavian artery	The pseudoaneurysm disappeared spontaneously	balloon angioplasty	The pseudoaneurysm disappeared spontaneously
Sanchez-Orightiz et al., 2003⁵⁰	56-year-old man	Kidney with lung mets	The patient was treated with RFA for the right kidney mass. Followup chest CT and abdominal MRI at 2, 5, 7 and 10 months after RFA revealed complete disappearance of the pulmonary metastases and lack of enhancement of the renal mass	mmunological response	The patient was treated with RFA for the right kidney mass. Followup chest CT and abdominal MRI at 2, 5, 7 and 10 months after RFA revealed complete disappearance of the pulmonary metastases and lack of enhancement of the renal mass
Lilienthal, 1913⁵¹	58-year-old female Mother of 5	Right breast with metastases to anterior axillary line at the seventh or eighth rib	After mastectomy and excision of secondary tumor, and Gwyer method, cancer did not return		After mastectomy and excision of secondary tumor, and Gwyer method, cancer did not return
Muroya, 2021⁵²	78-year-old man. history of HCC due to hepatitis C. End-stage renal disease (ESRD) due to diabetes. Hypertension. He had been prescribed metformin, pantoprazole, enalapril, felodipine, and metoprolol.	Lung	13 months later, the metastatic lesions suddenly decreased in size and number. Follow-up imaging showed no evidence of disease progression, and tumor makers were significantly decreased	may be attributed to hemodynamic changes associated with dyalisis	13 months later, the metastatic lesions suddenly decreased in size and number. Follow-up imaging showed no evidence of disease progression, and tumor makers were significantly decreased
Yang, 2021⁵³	55-year-old man. History of hypertension and left renal urolithiasis.	Kidney, adrneal gland	16 months after the treatment, a regression of the metastasis (3.4 cm) was observed. Twenty-two months after sunitinib treatment, a CT scan demonstrated a gradual reduction in the size of the adrenal metastasis (1.8 cm)	Gene mutations of the androgen receptor might be a possible mechanism of antiandrogen withdrawal syndrome, which causes the antiandrogens to act as partial agonists. A withdrawal of these antiandrogens can promote disease regression. Option B: immune induced by partial use of sunitinib	16 months after the treatment, a regression of the metastasis (3.4 cm) was observed. Twenty-two months after sunitinib treatment, a CT scan demonstrated a gradual reduction in the size of the adrenal metastasis (1.8 cm)
Freih-Fraih, 2022⁵⁴	79-year-old female	Kidney	At the light of this result, a review of the previous nephrectomy specimen was conducted, but failed to show viable neoplastic cells. With all of these findings, we interpreted the nephrectomy specimen as an example of complete spontaneous necrosis of a primary renal carcinoma.	most probably related to the surgical procedure.	At the light of this result, a review of the previous nephrectomy specimen was conducted, but failed to show viable neoplastic cells. With all of these findings, we interpreted the nephrectomy specimen as an example of complete spontaneous necrosis of a primary renal carcinoma.
Schaschula, 2024⁵⁵	60-year-old male. History of obesity, hypertension, and left ventricular hypertrophy.	Kidney	CT scan undertaken 11 months later revealed the right renal mass had largely regressed	the renal artery dissection compromised the tumour feeding vessel with thrombosis and infarction, causing spontaneous tumour regression.	CT scan undertaken 11 months later revealed the right renal mass had largely regressed
Ito, 2021⁵⁶	52-year-old man. History of CKD due to microvascular nephrotic syndrome and diabetic nephropathy. The patient had undergone a unilateral partial nephrectomy for renal cancer three years before.	radius	A second biopsy showed the almost complete disappearance of multinucleated giant cells and mature bone tissue, with no obvious neoplastic changes or malignant images	None reported	A second biopsy showed the almost complete disappearance of multinucleated giant cells and mature bone tissue, with no obvious neoplastic changes or malignant images
Teng et al., 1963⁵⁷	The patient was the fourth child of the family. The prenatal period was uneventful, and he was born through a normal delivery on December 10, 1960. The birth weight was 5 pounds, 4 1/2 ounces.		Complete spontaneous regression of the tumors in the bones was noted 16 months later.		Complete spontaneous regression of the tumors in the bones was noted 16 months later.
Grabstald, 1964⁵⁸	57 year-old Caucasian man		Numerous roentgenograms of the chest since thoracotomy have revealed no evidence of metastatic disease. The last films were made in 1963, almost five years after thoracotomy, and they showed normal findings. Recent intravenous pyelograms demonstrate no change from that observed in the original films.		Numerous roentgenograms of the chest since thoracotomy have revealed no evidence of metastatic disease. The last films were made in 1963, almost five years after thoracotomy, and they showed normal findings. Recent intravenous pyelograms demonstrate no change from that observed in the original films.
Wagle, 1972⁵⁹	57-year-old white male		Almost complete disappearance of the previously described lesions in the lower lung fields three months following surgery, no definite evidence of any metastatic lesions on chest x-ray six months after surgery, remission has persisted to the present time		Almost complete disappearance of the previously described lesions in the lower lung fields three months following surgery, no definite evidence of any metastatic lesions on chest x-ray six months after surgery, remission has persisted to the present time
Barré et al., 1986⁶⁰			The patient survived for another 5 years; the bronchioscopic and radioscopic tests were normal, and his general health was excellent.	The kind of stimulation of immune reaction provoked by bacterial infection was the foundation of numerous approaches to cancer therapy. We probably have, in the case of our first patient, the cause-effect relationship between staphylococcus pleural pneumonia and the regression of metastases one month after the infection.	The patient survived for another 5 years; the bronchioscopic and radioscopic tests were normal, and his general health was excellent.
Barré et al., 1986⁶⁰	A 49-year-old man		nodules disappeared 3 weeks later		nodules disappeared 3 weeks later
Smith & Herr et al., 1980⁶¹	A 72-year-old Caucasian male		A chest x-ray taken in October 1978 was normal and indicated complete resolution of all pulmonary metastatic disease	The factors that alter the tumor-host relationship to allow spontaneous regression of cancers are unknown	A chest x-ray taken in October 1978 was normal and indicated complete resolution of all pulmonary metastatic disease
Stapleton et al., 1981⁶²	A white male infant who weighed 4,460 grams at birth. His mother was 19 years old, gravida 1, para 0. The mother denied taking any medications, except prenatal vitamins and iron, during the pregnancy. There was no family history of renal disease, hypertension, liver disease, early deaths, or cerebral vascular accidents. The parents were not related.		By 6 weeks of age, the kidney size was normal, and at 2 years of age, the boy remains in good health with radiographically normal kidneys.		By 6 weeks of age, the kidney size was normal, and at 2 years of age, the boy remains in good health with radiographically normal kidneys.
Labrune et al., 1987⁶³	infants		disappearing within several months		disappearing within several months
Al-Derwish et al., 2003⁶⁴
Kumar et al., 2010⁶⁵
Schiavetti et al., 2009⁶⁶
Christophersen et al., 2006⁶⁷
Hensiek et al., 2000⁶⁸
Ishiyama et al., 2012⁶⁹
Kallmeyer, 2001⁷⁰
Kobayashi et al., 2002⁷¹
Masue et al., 2007⁷²
Rothermundt et al., 2009⁷³
Thoroddsen et al., 2002⁷⁴
Wada et al., 2003⁷⁵
Yanagihara et al., 2011⁷⁶
Kasat et al., 2001⁷⁷
Komaba et al., 2008⁷⁸
Miura et al., 2009⁷⁹
Weibl et al., 2009⁸⁰
Ricci et al., 2010⁸¹
Gleave et al.⁸²
Chow et al.⁸³
McDermott⁸⁴

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