This year the New England Journal of Medicine published one of a series of articles marking its 200 year anniversary. Entitled ‘Two hundred Years of Cancer Research’, the article is a useful reminder of just how far the understanding and treatment of cancer have come, not just in 200 years but in recent years as well.
In almost the first 100 years of the NEJM’s existence physicians could do little more than observe, measure and weigh tumours, but in 1863 Rudolf Virchow, with the help of a microscope, deduced the cellular origin of cancer. In 1889, Stephen Paget published his prescient ‘seed and soil’ theory of metastatic disease. But it was not until 1944 that Oswald Avery, a retired scientist Rockefeller University, through beautifully clear experiments with the pneumococcal bacillus, showed that cellular information is transmitted not by proteins but by DNA.
Thus Avery paved the way for Watson and Crick’s discovery in 1953 of the structure of DNA, which in turn would have profound effects on medicine and on cancer medicine in particular. The identification of genes that drive or suppress cellular growth and the complex regulation of signalling systems by which normal and cancer cells communicate with each other and their environment has enabled the drawing of a blueprint of ‘cancer cell machinery’. In turn this has led to the identification of individuals at increased risk of developing common cancers such as colon and breast.
If the understanding of cancer began its advance in the latter half of the 19th century, surgery was recognized as a form of treatment well before that. Ephraim McDowell removed an ovarian tumour – without anaesthetic – in 1809, the first abdominal operation in the US. In doing so he provided evidence that cancer masses could be cured by surgery. The introduction of anaesthesia (reported in the NEJM by John Collins Warren in 1846) and of antisepsis by Joseph Lister in 1867 paved the way for surgery as the primary mode of treatment for decades to come.
Since those early days surgical techniques have come far – notably more selective tissue removal and, relatively recently, the use of the adjuvant therapies of radiation or drugs, the potential of the former having been realized from the 1950s onwards and since refined to enable precise targeting of the energy beam in a calculated dose.
Experimentation with chemotherapy began as long ago as the early 1900s, but optimism about the use of chemicals grew in the 1940s with trials in lymphoma and childhood leukaemia. But it was not until the 1960s that major advances occurred in leukaemia in children and in Hodgkin’s disease in adults, and until the 1970s that the power of combinations of drugs was recognized. Now, following the demonstration that imatinib homes in on the unique molecular abnormality in chronic myeloid leukaemia, chemotherapy has become more of a targeted therapy, and there is an intensive search in progress for drugs to provide the hitherto elusive cures for tumours such as advanced melanoma and lung cancer.
For many years cancer treatment rested on the three pillars of surgery, radiotherapy and chemotherapy, used either alone or latterly in combination. More recently a fourth has been added: immunotherapy, as used in some lymphomas, metastatic melanoma and renal cancers.
In cancer prevention, while screening programs spring readily to mind, one of the biggest successes has been the persuasion of people that smoking is bad. Any decline in smoking-related cancer mortality (and morbidity) lags the decline in the percentage of smokers in the population, and in North America it took until the early 1990s for lung cancer incidence and mortality to begin falling. (But note that the incidence of smoking appears ‘stuck’, with lower socio-economic groups showing persistently high figures. And let us not forget that developing economies are regarded by tobacco companies as fertile ground.)
Two other notable preventive successes are vaccination against hepatitis B (hepatocellular carcinoma) and human papilloma virus (Ca cervix).
Of course, the NEJM did not discuss life and disability underwriting in its review of cancer developments over two centuries. With such a wealth of new treatments, screening programs (though debate continues in respect of some regarding cost-effectiveness and/or usefulness), and investigation techniques, it is hardly surprising that cancer mortality is falling. The NEJM article shows that since the mid-1970s, while cancer incidence has increased by about 10%, mortality per 100,000 population has decreased by about a quarter. This is evidence of a real medical success story.
So what does that mean for underwriting? For a start it does not mean that ratings should be reduced by 25% – or even a lower amount – across the board. Underwriters and their medical directors need to understand in which cancers the real improvements have taken place and in which sorts of risks. But, talking of rating reductions, it depends where you start from. Which in turn begs the question of how well ratings have kept up with the changing patterns of cancer mortality.
The classic method of rating cancer is the temporary extra premium. How much have ratings for individual cancers (by at least histology and stage) changed over the decades? Is that approach still valid? Experts say that cancer in future will become more of a chronic disease to be kept under control. That is already apparent in some leukaemias and related disorders. Even now, patients with extensive disease are being kept alive longer, and with a reasonable quality of life.
But while it is probably still generally true that after diagnosis and treatment of cancer the longer you survive the greater the likelihood you are cured, the pattern of mortality is not necessarily that implied by a temporary extra premium. Mortality in some stage III and IV (to use ‘old’ terminology, but you know what we mean) cancers has historically been surprisingly long term. Sure, it is good to have the insured pay a nice fat extra premium early, but if it doesn’t match the risk and the case is unlikely to complete…
The problems underwriting researchers have is that the traditional ratings are based on disease-free survival after treatment. You can scan the journals for as long as you like but stats of that nature are as rare as hens’ teeth. Overall mortality according to staging, yes. Relapse-free survival, yes. But the combination of the two in the detail one requires…?
Such is the position of anyone in search of an evidence base for cancer ratings. But that does not mean there is no need to try one’s hardest, and to keep ratings under review. One can’t help but suspect that cancer ratings deserve a penetrating review. Maybe applicants with a history of cancer are not getting the deal they deserve.
DeVita VT, Rosenberg SA. N Eng J Med 2012;366:2207-14 November 2012