- Case report
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Spontaneous regression of adrenal metastasis from renal cell carcinoma after sunitinib withdrawal: case report and literature review
© The Author(s). 2018
- Received: 14 May 2017
- Accepted: 30 October 2018
- Published: 14 November 2018
The spontaneous regression of metastatic renal cell carcinoma is a rare phenomenon, with an estimated incidence of < 1%. We report a case of post-nephrectomy renal cell carcinoma adrenal metastasis, followed by the spontaneous regression of the metastasis after withdrawal of sunitinib.
The patient was a 55-year-old male with clear cell type renal cell carcinoma who previously underwent a left laparoscopic radical nephrectomy. After 51 months of follow up, a recurrence in the left renal fossa was observed and subsequently excised. Four months after excision, an abdominal Computerized tomography (CT) identified an adrenal metastasis of 1.6 cm. The patient was treated with sunitinib. However, the treatment was discontinued because of gastrointestinal side effects and fatigue. Eleven months after the discontinuation of sunitinib treatment, a progression in the adrenal metastasis growth (5.7 cm) was observed, whereas 16 months after the discontinuation, a regression of the adrenal metastasis growth (3.4 cm) was observed. During subsequent follow-ups, a gradual reduction in the size of the adrenal metastasis (1.8 cm) was observed. After 44 months from the discontinuation of sunitinib treatment, the patient was still alive and followed up in the outpatient department.
Sunitinib is a multi-targeted inhibitor of vascular endothelial growth factor (VEGF) receptors. This compound reduces tumor angiogenesis and has been approved worldwide for the treatment of advanced renal cell carcinoma. To our knowledge, this is the fourth case of the spontaneous regression of metastatic renal cell carcinoma after the discontinuation of sunitinib treatment.
Approximately 21% of patients with renal cell carcinoma present with a metastatic disease at diagnosis, and 23% of patients who undergo radical nephrectomy for clinically localized disease develop metastasis/local recurrence during a 5-year follow-up . The spontaneous regression of metastatic renal cell carcinoma is a rare but well-known phenomenon, with an estimated incidence of < 1% . Several case reports have described the spontaneous regression of metastatic renal cell carcinoma. Such an occurrence has been associated with multiple different events that might influence the immune system, including primary tumor surgical debulking, radiation or embolization of the primary tumor, palliative hormonal treatment with tamoxifen, surgical abortion, and discontinuation of sunitinib treatment [3–6]. However, the exact mechanism remains unclear. We report a case of a post-nephrectomy adrenal metastasis of a renal cell carcinoma followed by the spontaneous regression of the metastasis after a short-term sunitinib treatment. To our knowledge, this is the fourth case of the spontaneous regression of metastatic renal cell carcinoma after withdrawal of sunitinib.
The spontaneous regression of cancer is defined as the partial or complete disappearance of a tumor without any treatment or with a treatment considered inadequate to exert a significant influence on the progression of cancer . The spontaneous regression of metastatic renal cell carcinoma following nephrectomy was first described by Bumpus in 1928 . It is a rare phenomenon, which is estimated to represent < 1% of renal cell carcinoma cases . The regression of metastatic sites has been reported to occur at the lungs and at other visceral organs including liver, bones, brain, choroid, pancreas, and adrenal glands . The mechanism of the spontaneous regression of renal cell carcinoma remains unclear. Humoral, immunological, and vascular factors, such as autoinfraction, have been previously proposed to be possible pathophysiologic mechanisms . Nephrectomy is not necessary and accounts for < 50% of the documented cases . Because the oncologic benefits of lymph node dissection in the management of renal cell carcinoma remain controversial , we routinely performed nephrectomy and renal fossa recurrent tumor resection without lymph node dissection.
Summary of published sunitinib withdrawal phenomenon cases
Dose and length of sunitinib treatment
Reason for discontinuing sunitinib treatment
Interval between spontaneous regression and sunitinib
Rothermundt, 2009 
bilateral adrenal glands, lung and bone
sunitinib 50 mg 4 weeks on and 2 weeks off, 10 months
Yanagihara, 2011 
bone and liver
sunitinib 50 mg per day, 11 days
thrombocytopenia and digestive symptoms
Teo, 2013 
50 mg/d, 4 weeks on and 2 weeks off for 6 months and 37.5 mg per day for 9 months
The mechanisms of spontaneous regression after an incomplete use of the multiple kinase inhibitor sunitinib remain unclear. Rothermundt et al. drew an analogy with the antiandrogen withdrawal syndrome of prostate cancer. Gene mutations of the androgen receptor might be a possible mechanism of antiandrogen withdrawal syndrome, which cause the antiandrogens to act as partial agonists. A withdrawal of these antiandrogens can promote disease regression .
Another possible mechanism is the immunomodulatory effect of sunitinib. Sunitinib improved the type-1 T-cell cytokine response in patients with metastatic renal cell carcinoma while reducing the T-regulatory cell function . Furthermore, sunitinib has been shown to inhibit the proliferation and function of human peripheral T cells and to prevent T-cell-mediated immune response in mice . In the present report, sunitinib treatment, or its discontinuation, might have modified the immune response.
The phenomenon of spontaneous regression after the discontinuation of sunitinib treatment may be masked by further treatment. The disease regression might have been missed or attributed to other second line therapies if our patient had not refused the suggestion of a right adrenalectomy. Thus, the number of patients with spontaneous regression associated with the discontinuation of sunitinib treatment may be underestimated, and this case report is a reminder of that for urologists.
Because recurrence has been reported after spontaneous regression , we will closely follow up our patient.
The authors are grateful to the operating room staff and ward staff of Mackay Memorial Hospital who participated in the management of this patient.
There are no sources of funding to be declared for this study.
Availability of data and materials
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
WRL did the clinical evaluation of the patient, came to a diagnosis and operated on the patient. TYY and AWC participated literature review and wrote the manuscript. All authors read and approved the final manuscript to be published. All authors agreed to be accountable for all aspects of the work.
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We received written consent for publication from the patient.
The authors declare that they have no competing interests.
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