Spontaneous regression of renal cell carcinoma: Reality or myth?

Abstract

Spontaneous regression of a malignant tumor is a very rare phenomenon. Renal cell carcinoma (RCC) is an aggressive malignancy with an often unpredictable behaviour. The incidence of spontaneous regression in metastatic RCC has been estimated to lie between < 1% and 7%. The spontaneous regression of a primary RCC has been reported much less commonly. Our literature review assesses the published literature concerning spontaneous regression of either primary or metastatic RCC. In order to examine this phenomenon in more detail we performed a literature search in the PubMed Database using the Keywords “renal cell carcinoma”, “metastatic disease”, and “spontaneous regression” and included reports from the last 100 years. The incidence of spontaneous regressions in RCC has always been considered a special feature of RCC compared to other solid malignancies. The majority of case reports of spontaneously regressed RCC describe the regression of metastases after nephrectomy rather than the spontaneous regression of a primary tumor. In cases of reported regression of metastatic RCC, this mostly applied to pulmonary lesions. As possible reasons for spontaneous regressions host immune defense mechanisms against metastatic RCC tissue following nephrectomy are discussed as important factor. RCC is known to be highly immunogenic and the possible existence of cytotoxic serum factors and tumor-specific surface antigens may trigger a cell-mediated cytotoxicity as an immunological basis for regression. Histological verification of supposed regression of a primary tumor may cause diagnostic difficulties, since large central areas of necrosis and cystic lesions of the tumor can occur simultaneously. The well-known phenomenon of necrosis in a fast growing RCC at the time of nephrectomy must not be confused with true spontaneous regression. Therefore, in our opinion such reported cases of supposed partial spontaneous regressions of primary RCCs are highly questionable. Most cases of spontaneous regression of RCC metastases have been reported after nephrectomy as the only treatment. Debulking by tumor nephrectomy then gives the immune system the chance to cope effectively with the remaining much lower quantity of tumour antigens. However, the mechanisms leading to spontaneous regression of metastatic lesions after cytoreductive nephrectomy are still poorly understood.

Keywords: Renal cell carcinoma, Spontaneous regression, Primary renal cell carcinoma, Metastatic renal cell carcinoma lesions, Cytoreductive nephrectomy

Core tip: Renal cell carcinoma (RCC) is an aggressive malignancy, which, from an immunological point of view, is highly variable. In the era of immunotherapy for metastatic RCC with interferon or interleukin it was always emphasized that spontaneous remissions of RCC, although comparatively rare, do occur and support the use of immunological therapies in metastatic disease. However, we suspected that this frequently cited occurrence of spontaneous remissions is more legend than reality. We therefore undertook an extensive literature search and included reports from the last 100 years in order to evaluate the scientific evidence describing spontaneous regressions of primary or metastatic RCC.