too early and too late cancer detection

In clinical practice, the suspicion of cancer leads to biopsy and biopsy generally requires surgical excision or removal of the lesion. As a matter of fact, sometimes the lesion turns to be benign (a cancer mimic) or premalignant (i.e. lacking the full features of malignancy) or, if malignant, to represent a very early step of the disease (and one cannot be sure that the tumor would have behaved as an aggressive disease if left untreated).  These possible events lead to overdiagnosis of cancer which is responsible for unjustified mutilation, anxiety of the patient, and cost escalation. A paper published in the  Journal of the National Cancer Institute in 2010 has stirred up another round of debate about this topic. To mitigate the ongoing problem of cancer overdiagnosis, the authors of the above paper suggest three possibilities: raising the threshold of labeling a test abnormal, waiting for the growth of a lesion over time before biopsying, and ignoring smaller abnormalities. In summary, we are realizing that it is better not to continue on the path where we are compelled to investigate and treat anything that resembles cancer. 

This is what is happening in the high-income developed countries of the world where screening procedures are highly effective in the detection of early cancer and its mimics. The best examples are cancer of the uterine cervix, the breast, the lung, etc. The opposite is true, instead, in the low-income developing countries where the above malignancies are detected too late due to the lack of resources in screening and secondary prevention, and the chance of successful treatment are low or null.  For example, it is estimated that over 1 million women worldwide currently have cervical cancer, most of whom (living in developing countries) have not been diagnosed, or have no access to treatment that could cure them or prolong their life. According to the World Health Organization, in 2005, almost 260 000 women died of the disease, nearly 95% of them in developing countries, making cervical cancer one of the gravest threats to women’s lives. In these areas, cervical cancer is the most common cancer in women and the leading cause of cancer death among women.

Patterns of cancer in developed and developing countries

 

In other posts I have been talking about the differences in rankings between developed and developing (low- and middle-income) countries in both incidence and mortality for cancer. The patterns vary by geography and economic status, which correlate roughly with the causes of cancer in the "environment" in its broadest sense.
The majority of cancers in more developed countries are those associated with more affluent lyfestyles - cancers of the lung, colon and rectum, breast, and prostate. In contrast, cancers of the liver, stomach, esophagus, and cervix - all related directly or indirectly to infectious agents - are relatively more common in developing countries.  The mix of common cancer in females varies as seen in the following table (source: Cancer Control Opportunities in low- and middle-income countries; see website in the list). Click to enlarge:

In developed countries the incidence of tumors of the breast, colon, lung and corpus uteri is higher than in low- and middle-income countries with a ratio, respectively, of 1.23/1; 1.95/1; 1.02/1; and 2.19/1. The mortality of these malignancies, however, is lower than in developing countries: breast 29.8% vs. 42.8%; colon and rectum 49.3% vs. 60.0%; lung 82.5% vs. 86.5%; and corpus uteri 21.32% vs. 33.8%. The higher mortality of these tumors in the developing world is mainly due to a significant delay in the diagnosis of the disease, i.e. the tumor is disclosed in a more advanced stage of progression, when therapy is less effective or useless. Because of these factors, the number of people dying of breast cancer and lung cancer in developing countries is likely to be equal to or even higher than the number of subjects dying of these tumors in the developed world.
In developing countries the incidence of tumors of the cervix uteri, stomach, liver, and esophagus, is much higher than in developed countries with ratios, respectively, of 6.49/1; 1.86/1; 4.08/1, and 8.12/1. The higher incidence of these tumors is broadly explicable by differences in exposure to certain infectious agents (HPV, HBV, HIV, etc) or carcinogens, but it is also strongly related to the lack of primary prevention (vaccination against HPV and HBV), to an ineffective secondary prevention (i.e., screening of carcinoma of cervix uteri), and to the lack of health facilities for early diagnosis and treatment. In fact, it is very frustrating to realize that in developing countries a significant proportion of people dying for cancer were suffering from preventable and/or curable malignancies. It is for this reason that all efforts should be made by the global cancer community to take immediate steps to slow and ultimately reverse the phenomenon.

Ho avuto già occasione di parlare delle differenze in termini di incidenza e mortalità dei tumori nei paesi sviluppati in confronto con quelli in via di sviluppo. Tali differenze si articolano in base alla geografia e alle condizioni economiche e quindi, in generale, alle condizioni ambientali nel senso più largo del termine. In genere, nei paesi sviluppati l'incidenza più elevata di alcune forme tumorali  (carcinoma del polmone, colon e retto, mammella e prostata) è correlata agli stili di vita più seguiti. Nei paesi in via di sviluppo, invece, si osserva una maggiore incidenza dei tumori associati, direttamente o indirettamente, all'esposizione ad agenti infettivi (carcinoma del fegato, della cervice uterina, dello stomaco e dell'esofago). Tutte queste forme tumorali sono molto aggressive ad eccezione, almeno in parte, del carcinoma della cervice uterina. La variabilità di incidenza e mortalità nel sesso femminile sono ben illustrate nella tabella.
Nei paesi sviluppati l'incidenza del carcinoma della mammella, colon, polmone, corpo uterino, è più elevata che nei paesi in via di sviluppo in ragione, rispettivamente, di 1.23/1; 1.95/1; 1.02/1; e 2.19/1.  La mortalità di questi tumori, però, è meno elevata che nei paesi in via di sviluppo: mammella 29.8% vs. 42.8%; colon e retto 49.3% vs. 60.0%; polmone 82.5% vs. 86.5%; corpo uterino 21.32% vs. 33.8%. Tutto ciò è dovuto al ritardo con il quale viene identificata la malattia che preclude l'efficacia delle terapie perchè il tumore si trova in una fase più avanzata. Come diretta conseguenza, la mortalità almeno per cancro della mammella e del polmone è più elevata nei paesi in via di sviluppo anche se l'incidenza è inferiore rispetto ai paesi sviluppati.
Nei paesi in via di sviluppo l'incidenza del carcinoma della cervice uterina, dello stomaco, del fegato, e dell'esofago è molto superiore a quella che si riscontra nei paesi sviluppati, in ragione, rispettivamente, di 6.49/1; 1.86/1; 4.08/1, e 8.12/1. L'incidenza più elevata è riconducibile alla diversa esposizione ad agenti infettivi (HPV, HBV, HIV, ecc) o carcinogeni, ma anche alla totale mancanza di misure di prevenzione primaria (vaccinazioni anti HBV o HPV), o all'insufficienza di misure di prevenzione secondaria (p.es. lo screening per il carcinoma della cervice uterina) e, infine, alla mancanza di strutture sanitarie che consentano una diagnosi precoce con relativo trattamento. E' sconfortante pensare che nei paesi in via di sviluppo la maggioranza dei decessi per cancro sia correlata a tumori prevenibili o curabili se diagnosticati in tempo. Tutto ciò deve rappresentare per la comunità globale che si occupa di cancro un motivo per attivarsi in modo fattivo affinchè tale tendenza venga ridotta o addirittura invertita.

Sign now for a cancer free world

The Union for International Cancer Control (UICC) is the leading international non-governmental organisation dedicated to the global prevention and control of cancer. It is set in Geneva, Switzerland, and was founded in 1933. UICC is the “custodian” of the World Cancer Declaration which is a call to action to substantially reduce the global cancer burden by 2020.The declaration was unanimously adopted at the World Leader’s Summit of policymakers, leaders & health experts during the 2008 World Cancer Congress in Geneva. The Declaration calls on the world to take immediate steps to reduce the global cancer burden and outlines 11 targets to be achieved by 2020. These include: 1) development of sustainable delivery systems to ensure that effective cancer control programmes are available in all countries; 2) improved measurement of the global cancer burden and the impact of cancer control interventions; 3) reduction of global tobacco consumption, obesity and alcohol intake levels; 4) effective widespread vaccination of populations in the areas affected by human papilloma virus (HPV) and hepatitis B virus (HBV); 5) improved public attitudes towards cancer by dispelling damaging myths and misconceptions about the disease; 6) improved diagnosis of many cancers when still localized through the provision of screening and early detection programmes; 7) increased access to accurate cancer diagnosis, 8) appropriate cancer treatments, supportive care, rehabilitation and palliative services for all patients worldwide; 9) increased access to effective pain control measures for all cancer patients in pain; 10) increased number of training opportunities available for health professionals in different aspects of cancer control; 11) achievement of major improvements in cancer survival rates in all countries. The declaration can be downloaded from the UICC website in different languages. Currently about 128000 people and 1035 organizations from all over the world have signed it. The reasons why everybody should do so are that cancer kills more people than AIDS, Malaria, and Tuberculosis combined, and the death toll is set to rise dramatically in the coming decades; two-thirds of cancer-related deaths occur in countries where resources available for cancer control are limited or nonexistent; without significant improvement, over 17 million people are projected to succumb from this disease by 2030; many cancers can be prevented, and several cancers can be cured if detected early and treated appropriately. This blog has been provided by a link to allow people to sign the Declaration (see the column on the right) . Let’s support such a call to action!