Population and registration area

Cali is the third largest city in Colombia, capital of the Department of Valle del Cauca. According to the 2005 census and according to the projections of the DANE ¹³, the estimated population for 2010 was 2.3 million inhabitants. 52% are females, and 26.2% self-identify as belonging to the black ethnic group ¹⁴. The life expectancy at birth is 73.1 years for men, and 78.5 years for females ¹⁵. The infrastructure for cancer care includes 165 oncology functioning services ¹⁶, these services are in the urban area where 95% of the population resides in an area of ​​approximately 110 km² that corresponds to 20% of the extension of the municipality of Cali (503 km²).

Incidence and mortality information

Information on the incidence of cancer was obtained from the database of the RPCC (2008-2012) and information on general mortality was obtained in the Municipal Public Health Secretary of Cali (2006-2015). Details on the history, objectives, logistics and coverage of the RPCC have been previously described ^5,17. This same issue of Colombian Medical describes in detail the procedures and methods for estimating incidence, mortality and survival in adults ¹⁸. In summary, the RPCC was established in 1962, it is a population-based cancer registry which provides continuous information on new cases of all types of cancer in permanent residents of Cali through active search and notification.

Implementation of a childhood cancer outcomes surveillance system (VIGICANCER) within Cali’s population-based cancer registry was carried-out in 2009; methodological details have been published recently ^19,20. Briefly, children and adolescents (<19 years of age) with new diagnosis of cancer and treated in a pediatric oncology unit of the city, are registered by the system and included in an active follow-up. VIGICANCER includes both children living in the city as well as children from other Colombian municipalities and provinces but treated in Cali. Vital status, relapse, treatment abandonment, and second neoplasms are the primary outcomes.

1. New cases of cancer (incidence)

In the quinquennium 2008-2012, 23,046 new cases of cancer were diagnosed among the permanent residents of Cali, for an average of 4,500 cases per year; 55% (12,613) occurred in females and the sex ratio was 1:2. The incidence rates standardized by age for all cancer sites per 100,000 person-years were 204.6 in men; and 185.1 in females. In the absence of other causes of death, the cumulative risk of developing cancer before reaching the age of 75 was 23.8% and 20.5% in males and females in Cali.

Cancer incidence rates per 100,000 person-year by sex and cancer location are shown in Table 1. In men, the five primary sites of primary cancer were prostate (ASR: 59.7), stomach (ASR: 20.2), colorectal (ASR: 16.2), lung (ASR: 14.5), and lymphomas (ASR: 11.3). Together they constituted 58.8% of all new cancer cases diagnosed between 2008 and 2012. Prostate cancer accounted for 28.2% of all incident cases, (n: 2,937).

In females, the most frequent locations for cancer according to their ASR were in descending order: breast (44.3), cervix (15.3), colorectal (14.0), thyroid (13.2), and stomach (10.7). These locations together accounted for 52.9% of all new cases of cancer diagnosed during the five-year period. Breast cancer alone accounted for 23.6% of incident cases (n: 2,972).

2. Mortality from cancer

Table 2 shows cancer deaths that occurred in Cali in two quinquennial periods; 2006-2010 and 2011-2015. During this decade there were 122,014 deaths, (56.8% in males and 43.2% in females). Overall mortality from cancer corresponded to 19.6% (23,873 deaths) of all deaths in that period and the number of deaths from this cause was greater among females (53.0%, 12,663) than among males (47.0%, 11,219). For the analysis of cancer mortality, emphasis was placed on the results of the quinquennium 2011-2015.

Cancer was the third cause of death in Cali after mortality due to cardiovascular diseases (26.0%) and unintentional or intentional injuries (20.1%).

In contrast to the number of deaths, standardized cancer mortality rates for all combined locations per 100,000 person-years were higher among males (107.0) than among females (85.9). Cancer of stomach, lung, colorectal, breast and prostate were the main causes of cancer-related death, together they represent approximately half of all cancer deaths (47.9%).

Based on mortality rates standardized by age, prostate cancer (ASR: 17.4), was the leading cause of death among tumors in males in the five-year period 2011-2015, followed by cancer of stomach (ASR: 14.4), lung (ASR: 14.4), colorectal (ASR: 10.2) and lymphomas (ASR: 6.0). Breast cancer was the leading cause of death in females (ASR: 13.8), followed by cancer of stomach (ASR: 8.2), colorectal (ASR: 7.5), lung (ASR: 7.3) and cervix (ASR: 6.5).

3. Changes in cancer morbidity and mortality

Tables 1 and 2 show the APC that represents the average percentage of annual increase or decrease in cancer incidence and mortality rates during the periods 1962-2012 and 1984-2015, respectively. In describing the change, three well-defined patterns were detected: increased or decreased when the APC was significantly different from zero (two-tailed values ​​p <0.05); otherwise the term stable or flat was used.

The incidence rates for all cancer body sites increased in male an annual average of 0.6% (95% CI: 0.4 - 0.8) and remained stable in females. In contrast, mortality for all cancer body sites has been significantly decreasing at an annual average of 0.9% in male; (95% CI: -1.1; -0.6); and 1.3% in females, (95% CI: -1.4, -1.1).

4. Five-year net survival

For the analysis, a total of 38,671 patients diagnosed with cancer were included through 1995-2009. The distribution of the most frequent malignancies corresponded to breast (17.7%), prostate (17.3%), stomach (13.1%) and colorectal cancer (9.4%), while a smaller number of records were reported for liver cancer (2.2%), melanoma (1.8%), multiple myeloma (1.5%) and Hodgkin's lymphoma (1.0%). The median age at diagnosis for the period considered was 64 years. There has been an increase in the number of patients diagnosed for the last study period 2005-2009. The trend of net survival for certain types of cancer by sex and diagnosis period 1995-2009 is shown in Figure 1.

Figure 1 Cali, Colombia. Net standardized survival by age at 5 years for the most frequent locations by period of interest and sex, between 1995 and 2009. 

Figure 2 shows the 5-year net survival standardized by age for three quinquennial periods: 1995-1999, 2000-2004 and 2005-2009. When compared with previous periods, patients diagnosed with cancer in the most recent period (2005 -2009) marked improvements in net survival of 5 years were observed for most cancer sites. The proportions of increased cancer survival in females could be explained in part by common types of cancer in females (e.g. thyroid, breast, and cervical cancers) that have a relatively good prognosis. When examined by year of diagnosis and localization of cancer, in general terms it was evident that in the last period which includes the years 2005-2009 there was an increase in survival for most of the cancer locations except for stomach cancer and colorectal cancer.

Figure 2 Cali, Colombia. Five-year net survival standardized by age after diagnosis by period of interest, both sexes between 1995 and 2009. 

In the case of liver cancer, age standardization was not carried out, because some of the age-specific 5-year net survival estimates necessary to carry out standardization were not available (very low survival, first year of follow-up, about 90% of patients with liver cancer died).

On the other hand, the highest estimates of net survival for the period 2005-2009 were seen for thyroid cancer (89.3%), prostate (83.2%), breast (74.4%) and melanoma (65.8%). In the case of hematolymphoid neoplasms, survival was better in patients with Hodgkin lymphoma (64.4%) than in non-Hodgkin lymphoma (43.3%). In leukemia and multiple myeloma survival was lower, with estimates for the 2005-2009 period of 28.1% and 22.8% respectively.

Childhood cancer

VIGICANCER registered 1,428 children (<15 years of age) and adolescents (15 to 18.9 years of age) between 2010 and 2016. Ninety-six percent (n: 1,379) contributed to the follow-up (673 hemato-lymphoid tumors y 706 solid tumors). Children 5-year overall survival (OS) was 52.0% (95% CI: 48.7, 55.3) and 44.0% (95% CI: 35.4, 52.2) in adolescents.

Table 3 shows OS by the International Childhood Cancer Classification 3rd version ²¹ cancer group. Group I was the most frequent both in children (39.7%) and adolescents (30.3%). Within this group 79.1% were acute lymphoblastic leukemia (ALL). Among group II, 38.4% were Hodgkin disease, 38.3% non-Hodgkin lymphoma (without Burkitt) and 23.3% Burkitt. From all groups, 17.2% were central nervous system tumors (group III); being the most frequent (26.5%) in the <1 year of age group.

Infancy and early childhood malignant solid tumors frequency was 2.3% for neuroblastoma (and other group IV tumors), 4.2% for retinoblastoma (group V), 3.9% for Wilms tumor (and other groups VI tumors), and 1.3% hepatoblastoma (group VII).

Malignant bone tumors (group VIII) were more frequent in adolescents (14.9%) than in children (5.6%), with 58.9% osteosarcomas and 32.7% Ewing sarcoma. Group IX (soft tissue sarcomas) was similar in children and adolescents (5.0% vs. 5.9%). Germ cell tumors (group X) showed an overall frequency of 5.2%; in children 3.4% and in adolescents 9.4%. Epithelial malignant tumors (group XI) had higher frequency in adolescents (12.9%) than in children (2.4%). In this group, thyroid tumor was the most frequent 51.5%. Non-specified cancers (group XII) were 1.3%.

Cancer related to infectious agents

The incidence and mortality rates for stomach and cervix uteri cancer have decreased significantly over the last 55 years (Fig. 3). The descent is monotonic, continuous and began before knowing the prominent role in the processes of carcinogenesis of Helicobacter pylori²⁸ and the Human Papilloma Virus (HPV) ²⁹. These changes are not related to specific interventions against these infectious agents, they are the result of progress in the development and improvement of sanitary conditions. Economic development determined changes in lifestyles and modifications of the known risk factors for gastric cancer. Refrigeration facilitates the consumption of fresh foods and limits the use of chemical-based food preservation methods (salting, desiccation, smoking, and acidification).

In the 21st century, gastric cancer still represents a great social burden in Cali and Colombia because it causes the highest number of deaths from cancer ^3,5,22. The disease is fatal when discovered clinically because the diagnosis is usually made in the advanced stages. From 1995 to 2009, the 5-year net survival of patients with gastric cancer in Cali was less than 20%, with a healing fraction of 15% and an average survival time of 6 months for uncured cases ²²; similar results were observed in Chile and Costa Rica. But in other Latin American countries with equal or lesser development, the survival estimates were around 30%, which are comparable to those observed in the United States and Europe. It is also possible that estimates of gastric cancer survival in Ecuador and Cuba may be overestimated ^24,25.

Despite the continuous decline in the incidence and mortality of infection-related cancers, rates remain high and the number of cases continues to increase due to aging and population growth ³⁰. It is very likely that this downward trend will continue, even without additional interventions, in the years to come; however, under natural conditions, it will likely take many decades, if not centuries, before the incidence and mortality rates reach the values ​​currently observed in the United States and Europe. It is a priority to implement additional measures to accelerate the decline, improve survival and achieve control ³⁰.

The perspectives for the control of gastric cancer are uncertain because therapeutic advances are insufficient, the pre-clinical results of efforts to develop vaccines against H. pylori have been disappointing ³¹; and the early detection of gastric cancer in Latin America has shown unreliable results ^32,33 and low cost-effectiveness ³⁴. During the first stages of tumor growth, cancer is clinically silent. Therefore, an alternative to control, is the implementation of primary prevention programs which would help eradicate H. pylori infection by reducing the risk of developing gastric cancer in people without precursor lesions ^30,34,35. Due to the above, it is necessary to develop 1) monotherapies to facilitate adherence to antibiotic treatment and 2) accurate non-invasive tests to identify premalignant gastric lesions and thus serve as a risk stratification tool of patients. The simultaneous detection of serum pepsinogens and antibodies against H. pylori has achieved this goal in Japan ^35,36. This strategy has not been adequately validated in Latin America and continues to be an option that requires exploration with a well-founded project of implementation.

The picture is different and more favorable for females with cervix uteri cancer (CUC). Mortality rates in Cali are close to the PDPCC goal ⁴, but they are still three times higher compared to the United States and Europe; where the risk of cervix uteri cancer is half of that observed in Cali. The incidence and mortality rates have declined for many reasons, including declining fertility rates, improved socio-economic conditions and the establishment of a citywide program to prevent cervix uteri cancer via a widespread use of pap smear ^29,37.

The knowledge that certain genotypes of VPH infection are necessary to cause cervix uteri cancer has created new strategies for its prevention in the current PDPCC. As of 2012, the national guidelines for vaccination against VPH are established and coverage of 80% has been achieved, which unfortunately is now below 10% because of a mismanaged episode of massive psychogenic reaction in Carmen de Bolívar, a Colombian rural region. This reaction was supposedly associated with the VPH vaccine ³⁸. To increase the accuracy of cervix uteri screening, the Ministry of Health of Colombia incorporated HPV testing in cervical cancer screening programs. It is expected to achieve coverage of 80% of the target population in 2021 ⁴. These measures are essential to accelerate the control of this disease because the 5-year net survival of females with cervix uteri cancer in Cali was 57%, 10% points below that observed in affluent countries ^24,25.

Cancer related opportunity screening activities

Prostate and breast cancer are the leading cause of cancer-related morbidity in males and females in Cali, respectively ⁵. In Colombia there are no organized screening programs for either cancer and cancer control is based on specific opportunistic screening activities. Mammography, digital rectal examination and PSA allowed us to detect cases of disease that were previously unknown and contributed to increasing the incidence rates before the first quinquennium of the 21st century and since then, it has begun to decline. Most, but not all, of the increase may be due to earlier detection of the disease. Once the use of screening tests had been established the rates tended to stabilize as long as other factors causing the disease had not changed.

These changes were more evident in the population subject to screening, the group of 50-69 years of age, where there was also a turning point in the trend of incidence. Similar changes were documented in Costa Rica and Ecuador at the end of the first decade of the 21st century and were observed in Europe and the United States 20 years earlier.

Mortality from prostate cancer has decreased consistently since 1984 with an average annual percentage decrease of 2%; the decline occurred earlier than expected. This could not be attributed exclusively to the screening activities (Fig. 3). An influential and perhaps determining factor is the evolution of treatments with curative intent; it is likely that the use of PSA and digital rectal examination have contributed to maintaining and consolidating this trend ³⁹. However, mortality from breast cancer remained stable during the study period (Fig. 3).

The United States and Europe have made great advances in the control of prostate and breast cancer. Despite the high incidence rates (ASR: 119.8 and ASR: 124.9, respectively); the 5-year net survival is around 98.9% and 89.7%; and mortality rates around (ASR: 20.1, ASR: 21.2), respectively ^11,24. In Cali, 5-year net survival for the same neoplasms was 83.2% and 74.4%; and the mortality rates around (ASR: 17.4 and ASR: 13.8), respectively. The existence of a gap of 15 percentage points in 5-year net survival in a population where incidence rates are half of those observed in affluent countries ⁴⁰, suggests that the diagnosis of cases is made at more advanced stages and / or that the tumors are more aggressive. This will remain an area of future investigation.

The incidence and mortality due to colorectal cancer continues to rise in males and females in Cali. The reasons are that the screening activities are incipient, and the risk factors are difficult to control or are not clearly identified ⁴¹; it is a priority to promote an organized screening program to reverse the current trend. Until this intervention occurs, oncological care services must be oriented to the early diagnosis of suspected cases.

Cancer related to tobacco use

The trend in the incidence of lung cancer correlates with the historical patterns of prevalence of cigarette smoking and there is sufficient evidence of a causal relationship between cigarette smoking and various types of cancer. The reduction in the number of cancer cases related to tobacco use in Cali, has been interpreted as a successful example of cancer control. This was due to the implementation of a very strong anti-smoking government campaign implemented in the seventies and that has been consolidated in the 21st century. The incidence rates of lung cancer for both sexes in Cali reflect the end of a tobacco-related epidemic that began in the 1970s and was interrupted around the 1980s ^5,42,43. Since then, there has been a significant decrease in tobacco-related cancer incidence and mortality: oral cavity and pharynx, esophagus, pancreas, lung and urinary bladder. The decrease was more consistent in the oral cavity and lung cancer in both males and females.

Net survival estimates

Surveillance of cancer survival is important for health organizations, civil society and research agencies because it serves to formulate strategies and prioritize cancer control measures, and to evaluate effectiveness, as well as the cost effectiveness of these strategies ¹.

At the beginning of the 21st century, we began to monitor trends in cancer survival in Cali. The relative survival (without age-adjustment) was estimated for 16,064 patients diagnosed with prostate, breast, colorectal, cervical, stomach and lung cancer through 1995-2004 ²². The present study, covers 38,671 patients diagnosed with invasive primary cancer in 14 body locations representing around 71.8% of the global cancer burden in Cali (15-year period 1995-2009). Furthermore, the accuracy of the previous estimates was improved through the implementation of the new unbiased Pohar-Perme estimator ^(44-46.

Coinciding with the implementation of the new health system in the 1990s, survival improved for most of the neoplasms in the first five-year period of the 21st century compared to the 1995-1999 period. This trend stagnated in the five-year period 2005-2009. The 5-year net survival was like that found in Argentina, Chile, Ecuador and Costa Rica and very low compared to that observed in developed countries ²⁴.

Certification of cancer mortality

Information on cancer mortality in liver, lung, brain and bones should be interpreted with caution, because in these sites, the occurrence of metastasis is frequent. In the Cali cancer registry, we found evidence that the primary site of some of these cancers came from locations different than these organs. It is important to understand that 45% of liver cancer cases corresponded to metastasis. It was also established that cancers of the bone (46%), lung (15%) and CNS (10%) corresponded to metastasis. There were 2,447 new cases and 450 deaths from cancer. The coding of the body locations made by the vital statistics office and the cancer registry were compared. The concordance (Landis criteria ⁴⁷ for the coding of cases of liver, bone and lung cancer were considerable (Kappa = 0.64, 0.67 and 0.79, respectively) and the highest was for malignant tumors of the CNS (Kappa = 0.90).

Childhood cancer

About 200,000 new childhood cancer cases per year are diagnosed in the world ⁽⁴⁸, 84% occurring in low and middle-income countries ^(49,50. Taken into account that cancer in children is not amenable to primary or secondary prevention, survival is the most relevant metric to evaluate efforts aimed to control cancer burden in this population group. Cali’s 5-year OS (51%) is 26% to 32% lower to outcomes reported in more affluent countries (77% to 83%) ^51,52. This implies that if in Colombia 1,500 to 1,600 children are treated for cancer per year then after 5 years 765 to 816 had died, and 390 to 512 would be preventable deaths. This survival gap persists in all cancer groups, except for Hodgkin disease (7% difference; 5-year OS: 88% vs 95%). Effectiveness decrease in cancer treatment is mainly related to intensity lost. Chemotherapy intensity is related both to dose and time interval among doses. Therefore, effectiveness of treatment is very dependent on the delays in treatment administration (adherence to treatment), being treatment abandonment the extreme example of this principle. Intensity lost has multifactorial causes involving the patient, their families, health providers, and the health system. Other path to reduce survival is due to treatment mortality and not because disease. This adverse outcome is both related to access to supportive care and advance disease at diagnosis. Access to timely and correct diagnosis and treatment is particularly related to poor outcomes in tumors that are dependent of the stage at diagnosis to achieve cure; retinoblastoma is the best example of this. Nevertheless, in the Latin-American context, the Argentinian hospital registries system reports a 3-year OS of 61.7% ⁵³, which compares favorably with Cali´s 3-year OS of 56.6% for this cohort.

Limitations

RPCC does not actively monitor adults, and Cali lacks reliable statistics on population migration ¹³. The RPCC has information about the cause of death through death certificates, but in some cases it can be difficult to determine if cancer is the basic cause of death.

Strengths

The RPCC has participated in many other collaborative studies and has been an advisor to the Colombian government in the evaluation of PBCR in the country and its data have contributed significantly to different aspects of cancer control in Colombia. The collaborative work with the SSPM of Cali facilitates access to information on general mortality and cancer; and allows an independent source of verification of new cases of cancer. Access to the information system of the Ministry of Health (SISPRO) and to the assurance databases provides a permanent update of the vital status and date of last contact.