Spontaneous regression of cancer.

Spontaneous regression of cancer is one of the most fascinating phenomena observed in medicine. It is generally regarded as inexplicable, although there are now some laboratory studies of regressed or regressing tumours, as well as new theoretical possibilities about mechanisms. In this review, the historical background, clinical features and possible mechanisms are discussed. The clinical aspects of the malignancies most often reported to undergo spontaneous regression, namely renal cell carcinoma, neuroblastoma, carcinoma of the breast, malignant melanoma and leukaemias/lymphomas, are reviewed. The prevalent view regarding the mechanism for spontaneous regression is the involvement of immunological factors in the host. Other mechanisms include hormonal changes, tumour necrosis, trauma and changes in blood supply. Recent. reports suggest other mechanisms such as apoptosis and differentiation to a benign tumour. Decreased telomerase activity has been reported in neuroblastomas that regress, and hypomethylation of DNA in retinoblastoma is a possibility. A role for cytokines and/or growth factors is also discussed. The significance of spontaneous regression is the demonstration of endogenous control of neoplastic growth. Spontaneous regression of cancer is defined as the complete or partial disappearance of malignant tumour in the absence of therapy that is capable of inducing anti-neoplastic effects. Most patients ultimately relapse, so it is not usually associated with cure of the malignant disease. The existence of spontaneous regression is often questioned; indeed, review of the literature reveals reported cases which do not represent malignant disease, instances in which documentation of metastases is questionable and some reported cases in which therapy may have played a role. In 1966, Everson and Cole published a classic monograph on this topic which included 176 welldocumented cases of spontaneous regression of cancer published from 1900 until 1964, and listed criteria for the diagnosis (1). These are: documented histologic regression of biopsy-proven metastases; radiologic regression of