Have the recent advancements in cancer therapy and survival benefitted patients of all age groups across the Nordic countries? NORDCAN survival analyses 2002-2021.

BACKGROUND: Since the early 2000s, overall and site-specific cancer survival have improved substantially in the Nordic countries. We evaluated whether the improvements have been similar across countries, major cancer types, and age groups. MATERIAL AND METHODS: Using population-based data from the five Nordic cancer registries recorded in the NORDCAN database, we included a cohort of 1,525,854 men and 1,378,470 women diagnosed with cancer (except non-melanoma skin cancer) during 2002-2021, and followed for death until 2021. We estimated 5-year relative survival (RS) in 5-year calendar periods, and percentage points (pp) differences in 5-year RS from 2002-2006 until 2017-2021. Separate analyses were performed for eight cancer sites (i.e. colorectum, pancreas, lung, breast, cervix uteri, kidney, prostate, and melanoma of skin). RESULTS: Five-year RS improved across nearly all cancer sites in all countries (except Iceland), with absolute differences across age groups ranging from 1 to 21 pp (all cancer sites), 2 to 20 pp (colorectum), -1 to 36 pp (pancreas), 2 to 28 pp (lung), 0 to 9 pp (breast), -11 to 26 pp (cervix uteri), 2 to 44 pp (kidney), -2 to 23 pp (prostate) and -3 to 30 pp (skin melanoma). The oldest patients (80-89 years) exhibited lower survival across all countries and sites, although with varying improvements over time. INTERPRETATION: Nordic cancer patients have generally experienced substantial improvements in cancer survival during the last two decades, including major cancer sites and age groups. Although survival has improved over time, older patients remain at a lower cancer survival compared to younger patients.

Improving communication of cancer survival statistics-feasibility of implementing model-based algorithms in routine publications.

BACKGROUND: Routine reporting of cancer patient survival is important, both to monitor the effectiveness of health care and to inform about prognosis following a cancer diagnosis. A range of different survival measures exist, each serving different purposes and targeting different audiences. It is important that routine publications expand on current practice and provide estimates on a wider range of survival measures. We examine the feasibility of automated production of such statistics. METHODS: We used data on 23 cancer sites obtained from the Cancer Registry of Norway (CRN). We propose an automated way of estimating flexible parametric relative survival models and calculating estimates of net survival, crude probabilities, and loss in life expectancy across many cancer sites and subgroups of patients. RESULTS: For 21 of 23 cancer sites, we were able to estimate survival models without assuming proportional hazards. Reliable estimates of all desired measures were obtained for all cancer sites. DISCUSSION: It may be challenging to implement new survival measures in routine publications as it can require the application of modeling techniques. We propose a way of automating the production of such statistics and show that we can obtain reliable estimates across a range of measures and subgroups of patients.

Survival in neuroendocrine neoplasms; A report from a large Norwegian population-based study.

Neuroendocrine neoplasms (NENs) are heterogeneous tumors originating from neuroendocrine cells. Their malignant potential varies from indolence to high-grade malignancy (carcinomas). We studied the survival of all NENs in Norway according to malignant potential and different primary sites. We identified all NEN cases diagnosed in 1993 to 2015 and reported to the national population-based Cancer Registry of Norway. We included 62 morphological types. According to morphological characteristics and known disease behavior, we stratified the tumors into two different groups: low/intermediate aggressiveness and high aggressiveness. A total of 17,128 NENs were analyzed. Median age was 67 years and 47.6% were females. The most common primary sites were in the lungs and the gastroenteropancreatic (GEP) system. The 5-year relative survival in patients with low/intermediate aggressive NENs was 64.8% (95% CI, 63.3-66.2) and high aggressive NENs 8.4% (95% CI, 7.8-9.1). Females had higher survival rates than males (p <0.001). The relative 5-year survival rate in patients younger than 50 years was 89.1% (95% CI, 87.4-90.7) vs 41.0% (95% CI, 34.9-46.9) in patients ≥80 years. In multivariable analysis gender, age at diagnosis, time of diagnosis, stage and primary sites were all predictors of outcome both in patients with low/intermediate tumors and high aggressive tumors. Survival improved significantly over time, regardless of sex, age and tumor stage.

Trends in Incidence of Neuroendocrine Neoplasms in Norway: A Report of 16,075 Cases from 1993 through 2010.

BACKGROUND: Epidemiological studies show an increasing trend in the incidence of neuroendocrine neoplasms (NENs). A significant number of NENs occur in less common primary sites, but they are often excluded from the population-based studies. We studied the incidence trends of all NENs in Norway according to different primary sites. MATERIALS AND METHODS: Our analyses were based on cancer cases diagnosed between 1993 and 2010 and reported to the national population-based Cancer Registry of Norway. A total of 65 morphological codes were identified as neuroendocrine and stratified into 3 different groups of aggressiveness: low, intermediate and high. RESULTS: We identified 16,075 NENs of which 49.5% were in women. The median age at diagnosis was 65 years. The most common primary sites were the lung (48.1%) and the gastroenteropancreatic system (18.0%). Stage at diagnosis was local in 40.4% of the cases, regional in 17.5% and distant in 42.1%. The stage distribution was stable throughout the study period. The age-standardized (European) incidence rate (per 100,000 person-years) increased from 13.3 in 1993 to 21.3 in 2010 with an estimated annual increase of 5.1% in women and 2.1% in men. The increase was most pronounced for tumors of intermediate aggressiveness from 3.3 in 1993 to 7.3 in 2010. The largest annual increases were estimated for the adrenal gland (8.8%), the pancreas (6.9%) and the lungs (6.1%). CONCLUSION: The incidence of NENs increased. Most primary tumors were found in the lungs or in the gastroenteropancreatic system. The increase in the incidence differed according to the primary site, gender and tumor aggressiveness.

Proportion cured models applied to 23 cancer sites in Norway.

Statistical cure is reached when a group of patients has the same mortality as cancer-free individuals. Cure models predict the cured proportion and the median survival of fatal cases. Cure models have seldom been applied and tested systematically across all major cancer sites. Incidence and follow-up data on 23 cancer sites recorded at the Cancer Registry of Norway 1963-2007 were obtained. Mixture cure models were fitted to obtain trends and up-to-date estimates (based on period approach) assuming cured and uncured groups exist. The model converged for cancers of the mouth and pharynx, oesophagus, stomach, colon, rectum, liver, gallbladder, pancreas, lung and trachea, ovary, kidney, bladder, CNS, non-Hodgkin lymphoma (only for males) and leukemia. The proportion of cured patients increased 1963-2002 for both sexes, with the largest changes (in percent) seen for leukemia (46.4 and 46.7) and CNS (35.9, 42.0), males given first. Median survival time for the uncured cases increased for colon and rectal cancer, and there was a three- fold increase in median survival time for patients with fatal ovarian cancers. Cancers of bladder and CNS had the highest up-to-date proportion cured (in percent), 67.4 and 64.0, respectively, pancreas and liver were amongst the lowest (5.7 and 9.9, respectively). Cure models are useful when monitoring progress in cancer care, but must be applied and interpreted with caution. The absolute estimates of the cure proportion are speculative and should not be calculated where cure is not medically anticipated.

Nordcan.R: a new tool for federated analysis and quality assurance of cancer registry data.

Aim of the article: We present our new GDPR-compliant federated analysis programme (nordcan.R), how it is used to compute statistics for the Nordic cancer statistics web platform NORDCAN, and demonstrate that it works also with non-Nordic data. Materials and methods: We chose R and Stata programming languages for writing nordcan.R. Additionally, the internationally used CRG Tools programme by International Agency for Research on Cancer (IARC/WHO) was employed. A formal assessment of (GDPR-compliant) anonymity of all nordcan.R outputs was performed. In order to demonstrate that nordcan.R also works with non-Nordic data, we used data from the Netherlands Cancer Registry. Results: nordcan.R, publicly available on Github, takes as input cancer and general population data and produces tables of statistics. Each NORDCAN participant runs nordcan.R locally and delivers its results to IARC for publication. According to our anonymity assessment the data can be shared with international organizations, including IARC. nordcan.R incidence results on Norwegian and Dutch data are highly similar to those produced by two other independent methods. Conclusion: nordcan.R produces accurate cancer statistics where all personal and sensitive data are kept within each cancer registry. In the age of strict data protection policies, we have shown that international collaboration in cancer registry research and statistics reporting is achievable with the federated analysis approach. Undertakings similar to NORDCAN should consider using nordcan.R.

Epidemiology of pancreatic cancer in Norway: trends in incidence, basis of diagnosis and survival 1965-2007.

OBJECTIVE: Pancreatic cancer is the second most frequent gastrointestinal cancer in the Western world. Few reports on concomitant trends in pancreatic cancer incidence, diagnosis, mortality and survival exist at the national level. This study provides a baseline overview of the temporal patterns in these four indicators over the past four decades in Norway. MATERIAL AND METHODS: We analysed trends in incidence, basis of diagnosis, relative survival and mortality from the Cancer Registry of Norway for the period 1965-2007. RESULTS: Included were 21,663 patients with pancreatic cancers. Incidence and mortality rates remained at around 6-8 per 100,000 over the study period. Diagnoses based on clinical examination alone dropped from 12.5% (in the 1950s) to <1% (in the 2000s), while use of imaging techniques, such as CT and MRI, increased from 3.6% to >30%. Previously high rates of autopsy-verified diagnosis and non-therapeutic surgery decreased accordingly. Consistently more primary tumours (from 12.9% to 19.4%) and metastases (from 12.5% to 22.4%) had histological examination, and use of endoscopy increased to approximately 10%. Relative survival after diagnosis of pancreatic cancer remains very low. However, in recent years, a modest improvement in short-term survival has been noted, with 1-year survival rates of 18% and 16% for males and females, respectively. CONCLUSIONS: The incidence and mortality for pancreatic cancer remain largely unchanged, with few 5-year survivors. Improved short-term survival may reflect more aggressive use of surgery and chemotherapy. Further elucidation of risk factors in pancreatic cancer is needed to enable effective prevention, early detection and improved treatment strategies.

Suggested excess of occupational cancers in Norwegian offshore workers: preliminary results from the Cancer Registry Offshore Cohort.

OBJECTIVE: The aim of this communication was to report the overall incidence of cancer in a cohort of male Norwegian offshore oil workers. METHODS: The Offshore Cohort was comprised of >25,000 men who were employed at installations in the North Sea in the period 1965-1999, and who responded to a questionnaire that included work history offshore, other occupational experience, education, leisure-time activities, and lifestyle factors. Calculating standardized incidence ratios (SIR), we compared the number of prospective incident cancers diagnosed between 1999 and 2005 with those expected for age-, gender- and period-specific rates in the general Norwegian population. RESULTS: The overall cancer incidence did not differ from that of the reference population [SIR=1.0, 95% -confidence interval (95% CI) 1.0-1.1, N=695]. There were indications of excess risks of acute myeloid leukemia (SIR=2.0, 95% CI 1.0-3.7) and cancer of the pleura (SIR=2.2, 95% CI 0.9-4.6). No data on occupational history was used in these preliminary analyses. CONCLUSIONS: The cohort was relatively young and an extended observation period would be important for in-depth analyses. The suggested excess of leukemia and cancer of the pleura may be linked to occupational exposure during employment offshore; this issue needs to be addressed in further studies.

Rising Incidence and Improved Survival of Anal Squamous Cell Carcinoma in Norway, 1987-2016.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare, human papilloma virus-associated cancer. The purpose was to investigate the population-based incidence rates, age and gender distribution, and survival of ASCC. MATERIALS AND METHODS: All primary ASCC in 1987 to 2016 were identified in the Cancer Registry of Norway (N = 1548), with information on age, gender, stage, county of residence, radiotherapy, and survival. RESULTS: Median age was 66 years; 71% were females. World age-standardized incidence rates increased (1987-2016) from 0.79 (95% confidence interval [CI], 0.69-0.90) to 1.10 (95% CI, 1.00-1.22) per 100,000 person-years in females and, from 0.34 (95% CI, 0.28-0.42) to 0.47 (95% CI, 0.40-0.54) in males. Estimated annual percentage change was 1.7 (95% CI, 0.9-2.6) for females and 1.3 (95% CI, -0.1 to 2.7) for males. Incidence rates increased with age; the relative risk was higher in major cities. Five-year net survival increased from 63.4% to 72.7% (1987-2016), but for age ≥ 70 years remained ∼57%. Net survival was dependant on stage, age, and gender. Five-year net survival (1997-2016) was 76.4% after curative radiotherapy, and 18.0% after palliative radiotherapy. CONCLUSION: ASCC incidence rates increased from 1987 to 2016, and survival improved for patients < 70 years. Five-year net survival was 76% after curative radiotherapy in Norway.

Long-term Change in the Risk of Skin Cancer After Organ Transplantation: A Population-Based Nationwide Cohort Study.

Importance: The high risk of skin cancer after organ transplantation is a major clinical challenge and well documented, but reports on temporal trends in the risk of posttransplant cutaneous squamous cell carcinoma (SCC) are few and appear contradictory. Objective: To study temporal trends for the risk of skin cancer, particularly SCC, after organ transplantation. Design, Setting, and Participants: Population-based, nationwide, prospective cohort study of 8026 patients receiving a kidney, heart, lung, or liver transplant in Norway from 1968 through 2012 using patient data linked to a national cancer registry. The study was conducted in a large organ transplantation center that serves the entire Norwegian population of approximately 5.2 million. Exposures: Receiving a solid organ transplant owing to late-stage organ failure, followed by long-term immunosuppressive treatment according to graft-specific treatment protocols. Main Outcomes and Measures: Occurrence of first posttransplant SCC, melanoma, or Kaposi sarcoma of the skin. Risk of skin cancer was analyzed using standardized incidence ratios (SIRs) and, for SCC, multivariable Poisson regression analysis of SIR ratios, adjusting for 5-year time period of transplantation, different follow-up time, age, sex, and type of organ. Results: The study cohort included 8026 organ transplant recipients, 5224 men (65.1%), with a mean age at transplantation of 48.5 years. Median follow-up time was 6.7 years per recipient; total follow-up time, 69 590 person-years. The overall SIRs for SCC, melanoma, and Kaposi sarcoma were 51.9 (95% CI, 48.4-55.5), 2.4 (95% CI, 1.9-3.0), and 54.9 (95% CI, 27.4-98.2), respectively. In those who underwent transplantation in the 1983-1987 period, the unadjusted SIR for SCC was 102.7 (95%, 85.8-122.1), declining to 21.6 (95% CI, 16.8-27.0) in those who underwent transplantation in the 2003-2007 period. Adjusting for different follow-up times and background population risks, as well as age, graft organ, and sex, a decline in the SIR for SCC was found, with SIR peaking in patients who underwent transplantation in the 1983-1987 period and later declining to less than half in patients who underwent transplantation in the 1998-2002, 2003-2007, and 2008-2012 periods, with the relative SIRs being 0.42 (95% CI, 0.32-0.55), 0.31 (95% CI, 0.22-0.42), and 0.44 (95% CI, 0.30-0.66), respectively. Conclusions and Relevance: The risk of SCC after organ transplantation has declined significantly since the mid-1980s in Norway. Less aggressive and more individualized immunosuppressive treatment and close clinical follow-up may explain the decline. Still, the risk of SCC in organ transplant recipients remains much higher than in the general population and should be of continuous concern for dermatologists, transplant physicians, and patients.

An empirical comparison of methods for predicting net survival.

BACKGROUND: Providing accurate predictions of long-term net survival for recently diagnosed cancer patients is challenging due to the lack of follow-up. The aim of this study was to empirically compare predictions of net survival obtained from a flexible parametric excess hazard model to predictions obtained using the period and hybrid approaches. METHODS: The Cancer Registry of Norway was used to identify patients diagnosed with cancer during the period 1953-2008. Patients were then followed up for survival until the end of 2013. Net survival was calculated for 23 different cancer sites at 5, 10 and 15 years after diagnosis for each patient cohort. Observed net survival was estimated using the PP estimator. Predicted net survival was obtained omitting the most recent follow-up years using three approaches: a flexible parametric excess hazard model (FPM), the period approach, and the hybrid approach. All estimates were age-standardized to the age distribution of the cohort for which predictions were made. Prediction errors were calculated as the absolute difference between observed and predicted net survival. RESULTS: Average absolute prediction error across all cancer sites was smallest for FPM for 5-year, 10-year and 15-year net survival. FPM and the hybrid approach gave better predictions of 10- and 15-year net survival than the period approach. The period and hybrid approaches tended to over-estimate net survival for cancer sites with poor survival, and under-estimate net survival for cancer sites where survival has increased over time. Uncertainty in the predictions was considerably smaller when FPM was used compared to the other approaches. CONCLUSIONS: FPM should be considered for predicting net survival when follow-up is incomplete.

Subsite-specific dietary risk factors for colorectal cancer: a review of cohort studies.

Objective. A shift in the total incidence from left- to right-sided colon cancer has been reported and raises the question as to whether lifestyle risk factors are responsible for the changing subsite distribution of colon cancer. The present study provides a review of the subsite-specific risk estimates for the dietary components presently regarded as convincing or probable risk factors for colorectal cancer: red meat, processed meat, fiber, garlic, milk, calcium, and alcohol. Methods. Studies were identified by searching PubMed through October 8, 2012 and by reviewing reference lists. Thirty-two prospective cohort studies are included, and the estimates are compared by sex for each risk factor. Results. For alcohol, there seems to be a stronger association with rectal cancer than with colon cancer, and for meat a somewhat stronger association with distal colon and rectal cancer, relative to proximal colon cancer. For fiber, milk, and calcium, there were only minor differences in relative risk across subsites. No statement could be given regarding garlic. Overall, many of the subsite-specific risk estimates were nonsignificant, irrespective of exposure. Conclusion. For some dietary components the associations with risk of cancer of the rectum and distal colon appear stronger than for proximal colon, but not for all.

Body mass index, physical activity, and colorectal cancer by anatomical subsites: a systematic review and meta-analysis of cohort studies.

Several studies report varying incidence rates of cancer in subsites of the colorectum, as an increasing proportion appears to develop in the proximal colon. Varying incidence trends together with biological differences between the colorectal segments raise questions of whether lifestyle factors impact on the risk of cancer differently at colorectal subsites. We provide an updated overview of the risk of cancer at different colorectal subsites (proximal colon, distal colon, and rectum) according to BMI and physical activity to shed light on this issue. Cohort studies of colorectal cancer, published in English throughout 2010, were identified using PubMed. The risk estimates from 30 eligible studies were summarized for BMI and physical activity. A positive relationship was found between BMI and cancer for all colorectal subsites, but most pronounced for the distal colon [relative risk (RR) 1.59, 95% confidence interval (CI) 1.34-1.89]. For the proximal colon and rectum, the risk estimates were 1.24 (95% CI 1.08-1.42) and 1.23 (95% CI 1.02-1.48), respectively. Physical activity was related inversely to the risk of cancer at the proximal (RR 0.76, 95% CI 0.70-0.83) and distal colon (RR 0.77, 95% CI 0.71-0.83). Such a relationship could not be established for the rectum (RR 0.98, 95% CI 0.88-1.08). In conclusion, the results suggest minor differences in the associations of BMI and the risk of cancer between the colorectal subsites. For physical activity, the association does not seem to differ between the colonic subsites, but a difference was observed between the colon and the rectum, perhaps indicating that different mechanisms are operating in the development of colon and rectal cancer.

Population-based evidence of increased survival in human papillomavirus-related head and neck cancer.

BACKGROUND: Evidence from clinical, population-based and molecular studies has shown that human papillomavirus (HPV) infection can be a causal risk factor for a subset of head and neck squamous cell carcinomas (HNSCC). It is proposed that HPV-associated oropharyngeal cancer is a new disease entity that requires treatment and prevention strategies distinct from present recommendations. METHODS: In our population-based study we estimated incidence and survival trends in 8270 patients with HPV-related HNSCC (HPV(+)HNSCC) and HPV-unrelated HNSCC (HPV(-)HNSCC) in Norway over the past three decades. RESULTS: In the period 1981-1995, patients with HPV(+)HNSCC had poorer survival than HPV(-)HNSCC (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.14-1.44). By 1996-2007, survival had increased in both groups, but the increase was significantly greater among HPV(+)HNSCC patients (HR 0.57, 95% CI: 0.48-0.67). During the same period, incidence also increased, but only for HPV(+)HNSCCs. From 1981-1995 to 1996-2007, median age at diagnosis for HPV(+)HNSCC decreased from 63.2 to 59.8 years, while for HPV(-)HNSCC median age at diagnosis of 66.6 years remained unchanged. CONCLUSIONS: We demonstrate a population level improvement in survival among patients with oropharyngeal squamous cell cancers commonly related to infection with HPV. In contrast, patients with HNSCC not related to HPV only showed a modest improvement in survival in the period 1981-2007. A concomitant increase in incidence and survival was observed for HPV-related cancers only. This trend cannot be explained by changes in treatment, cancer registration nor screening, but is most likely due to an increased prevalence of HPV-positive tumours.

Smokeless tobacco use and risk of cancer of the pancreas and other organs.

Limited data are available on the carcinogenicity of smokeless tobacco products in organs other than the mouth. Snus is a smokeless tobacco product widely used in Norway. We studied 10,136 Norwegian men enrolled since 1966 in a prospective cohort study, 31.7% of whom were exposed to snus. The relative risk of pancreatic cancer for snus use was 1.67 (95% confidence interval [CI] = 1.12, 2.50); that of oral and pharyngeal cancer was 1.10 (95% CI = 0.50, 2.41), that of esophageal cancer was 1.40 (95% CI = 0.61, 3.24), and that of stomach cancer was 1.11 (95% CI = 0.83, 1.48). The relative risks of cancers of the lung (either all histological types or adenocarcinoma), urinary bladder and kidney were not increased among snus users. The increase in the relative risk of pancreatic cancer was similar in former and current snus users and was restricted to current tobacco smokers. Our study suggests that smokeless tobacco products may be carcinogenic on the pancreas. Tobacco-specific N-nitrosamines are plausible candidates for the carcinogenicity of smokeless tobacco products in the pancreas.