Inequalities in Survival from Cancer

While it may appear repugnant to reduce phenomena of human life to mathematical ratios, an arithmetical definition of cure was already being proposed in the 1920's for dealing with the results of treatment of chronic diseases. It was concluded that the term "cure" should be used only if the duration of observations were given, for instance, 3 or 5 years after the intervention''. The time of onset of a disease is generally taken as the beginning of clinical disease, when appearance of symptoms leads to a diagnostic intervention, and not the time of occurrence of the first (cellular, molecular) alteration(s) in the stepwise process leading to a chronic, degenerative disease. The "natural duration of disease", as the duration of life of untreated patients was called, and the duration of survival of treated patients were measured as the period between the time of diagnosis or therapeutic intervention (generally close to that of diagnosis) and death. The precocity and accuracy of the diagnosis obviously playa capital role. It was claimed that the increase in cancer mortality seen since the beginning of the century was due only to cases occurring at inaccessible sites, with no increase in cases at accessible sites, indicating that the increase was only apparent and due mainly to improved diagnostic methods. A study in the United Kingdom for the period 1897-1917 showed instead that the mortality rate had increased faster for cancers at accessible sites (56%) than for those at inaccessible sites (41%). Another tabulation suggested that mortality due to inaccessible cancers had increased much faster than that due to cancers at accessible sites in the period 19111929. At least some of the discrepancy between the two tables was attributed to uneven diagnostic criteria and to pronounced differences in cancer mortality between social classes. Individuals in the lowest social class had by far the highest mortality, mainly from cancers at "exposed sites'". Higher mortality in the less favored socioeconomic groups was thereafter confirmed by several studies3,9,IO,l4,2 l . Since it is more difficult to establish the time of onset of tumors of internal organs than of organs in which something tangible, a lump or a sore, can be observed, Greenwood' focused on breast cancer to demonstrate the usefulness of timely intervention. Untreated breast cancer patients had an average of 3.25 years' survival from the time of diagnosis, whereas the normal expected duration of life at age 55 (the average age at which breast cancer was diagnosed) was 18.87 years. Breast cancer patients who were treated when the disease was not too far advanced to make surgical intervention hopeless had a life expectancy of 5.74 years. Those who were treated when the cancer was strictly localized, did not involve the skin, and had not metastasized to the lymph nodes, had a life expectancy of 12.93 years. The net gain in years of life obtained by early therapeutic intervention was strongly emphasized", and the conviction that the fatal course of cancer could be interrupted and/or avoided gained ground, stimulating the development of surgery in the treatment of cancer and, later on, of cancer chemotherapy. The complexity of the estimation and the major determinants of the duration of survival have been extensively discussed I. Relatively little attention has been given to the role of different courses of disease in different individuals. It remained therefore unclear whether and to which extent the natural duration of disease might be altered not only positively by extending survival, but in some instances also by altering negatively the natural course of the disease. While stressing the vital importance of early intervention when a cancer is still localized, as Greenwood did 30 years earlier", Shimkin 18 warned that an accurate assessment of the success of therapy should also take into consideration possible differences in the natural course of disease in different individuals. A certain proportion of untreated cancer cases was reported to survive for 5 years and longer. Breast cancer cases appeared to be the "least malignant", with about 20% of untreated patients still alive 5 years after the onset of the clinical disease. For lymphoma and chronic leukaemia, the 5-year survival rate of untreated patients varied between 10% and 20%, whereas 5-10% of untreated patients with cancers of the bladder, prostate or rectum were likely to survive 5 years or longer! ", Shimkin's warning was justified at the time and for the long period during which therapeutic protocols were characterized by particular rigidity. However, it can be expected that molecular characterization (already possible for certain tumors) of the successive steps in the carcinogenesis process and in relation to different etiologic agents8,l3 and improved understanding of the response of transformed cells to antineoplastic agents? will allow the tailoring of more efficient interventions at the individual level.