Trends in patterns of treatment and survival of colorectal cancer patients using cancer registry data in Japan: 1995-2015.

Recent advances in treating colorectal cancer (CRC) have increased the importance of multidisciplinary treatment. This study aimed to clarify trends in the treatment and survival of CRC using population-based cancer registry data in Japan. We analyzed the survival of CRC cases diagnosed from 1995 through 2015 from a population-based cancer registry of six prefectures. The year of diagnosis was classified into five periods, and the trends in the detailed categorization of treatments and survival were identified. We calculated net survival and excess hazard of death from cancer using data on 256,590 CRC patients. The use of laparoscopic surgery has been increasing since 2005 and accounts for the largest proportion of treatment types in the most recent period. Net survival of CRC patients diagnosed after 2005 remained high for laparoscopic surgery and endoscopic surgery (endoscopic mucosal resection or endoscopic submucosal dissection). There was an upward trend in treatment with chemotherapy in addition to open and laparoscopic surgery. Using the excess hazard ratio at the regional stage since 2005, there has been a significant improvement in survival in the younger age group and the rectum cancer group. By type of treatment, there was a tendency toward significant improvement in the open surgery + chemotherapy group. We clarified the trends in treating CRC and the associated trends in survival. Continuous survey based on population-based data helps monitor the impact of developments in treatment.

Prevalence of survivors of childhood cancer based on a population-based cancer registry in Osaka, Japan.

Although the survival rate of patients with childhood cancer has greatly improved, long-term survivors face specific problems such as the late effects of cancer treatment. In this study, we estimated the number of people who had experienced childhood cancer to predict their needs for medical care and social resources. Using data from the population-based Osaka Cancer Registry, we identified children aged 0-14 years who were diagnosed with cancer between 1975 and 2019. We estimated the prevalence on December 31, 2019, and the 5- and 10-year prevalence (i.e., the number of survivors living up to 5 or 10 years after the diagnosis of cancer) over time. The prevalence proportion was age-standardized using a direct standardization method. The prevalence estimates for Osaka were applied to the national population to determine the national prevalence in Japan. Among 8186 patients diagnosed with childhood cancer in Osaka, 5252 (987 per million) survived until December 31, 2019. The 5-year prevalence per million increased from 194 in 1979 to 417 in 2019 (+116%), while the 10-year prevalence increased from 391 in 1984 to 715 in 2019 (+83%). Based on the long-term registry data, an estimated 73,182 childhood cancer survivors were living in Japan by the end of 2019. The increasing 5-year and 10-year prevalence proportions indicate the continued need for cancer survivorship support for children, adolescents, and young adults. These estimates of the prevalence of childhood cancer survivors, including long-term survivors, may be useful for policymakers and clinicians to plan and evaluate survivorship care.

Risk of thoracic soft tissue sarcoma after breast cancer radiotherapy: a population-based cohort study in Osaka, Japan.

Postoperative radiotherapy for breast cancer reportedly increases the risk of thoracic soft tissue sarcomas, particularly angiosarcomas; however, the risk in the Japanese population remains unknown. Therefore, this study aimed to investigate the incidence of thoracic soft tissue sarcoma among patients with breast cancer in Japan and determine its association with radiotherapy. This retrospective cohort study used data from the population-based cancer registry of the Osaka Prefecture. The inclusion criteria were female sex, age 20-84 years, diagnosis of breast cancer between 1990 and 2010, no supraclavicular lymph node or distant metastasis, underwent surgery and survived for at least 1 year. The primary outcome was the occurrence of thoracic soft tissue sarcomas 1 year or later after breast cancer diagnosis. Among the 13 762 patients who received radiotherapy, 15 developed thoracic soft tissue sarcomas (nine angiosarcomas and six other sarcomas), with a median time of 7.7 years (interquartile range, 4.0-8.6 years) after breast cancer diagnosis. Among the 27 658 patients who did not receive radiotherapy, four developed thoracic soft tissue sarcomas (three angiosarcomas and one other sarcoma), with a median time of 11.6 years after diagnosis. The 10-year cumulative incidence was higher in the radiotherapy cohort than in the non-radiotherapy cohort (0.087 vs. 0.0036%, P < 0.001). Poisson regression analysis revealed that radiotherapy increased the risk of thoracic soft tissue sarcoma (relative risk, 6.8; 95% confidence interval, 2.4-24.4). Thus, although rare, breast cancer radiotherapy is associated with an increased risk of thoracic soft tissue sarcoma in the Japanese population.

Prognostic impact of coexisting cardiovascular disease in patients with cancer: A multicenter retrospective cohort study.

Background: The incidence of malignancy and cardiovascular disease (CVD) is increasing worldwide. However, it is not entirely clear how the coexistence of CVD at the time of cancer diagnosis affects the overall survival of patients with cancer. Methods and results: We used the cancer registries and administrative claims data of patients diagnosed with cancer at 36 designated cancer care hospitals in Osaka, Japan, from 2010 to 2015. The Cox proportional hazard model was used to examine how coexisting CVD (heart failure [HF], ischemic heart disease, peripheral arterial disease, cerebrovascular accidents, and atrial fibrillation) affected overall survival and the impact of HF severity, as documented by the New York Heart Association (NYHA) classification. Of the 131,701 patients with cancer, 9704 had coexisting CVD. The 3-year survival rates for patients with and without coexisting CVD were 62.9 % and 77.6 %, respectively. The adjusted hazard ratio (aHR) for all-cause mortality for coexisting CVD was 1.47 (95 % confidence interval, 1.41-1.52). Among the CVD subtype, patients with coexisting HF had the poorest prognosis. The aHRs in patients with HF by NYHA classification, using the patients without HF as a reference, were as follows: Class I: 1.33 (p = 0.217); II: 1.68 (p < 0.001); III: 1.54 (p = 0.011); IV: 2.47 (p < 0.001). Conclusion: Coexisting CVD and HF severity at cancer diagnosis is associated with survival in patients with cancer.

Subsite-specific trends in mid- and long-term survival for head and neck cancer patients in Japan: A population-based study.

Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan. Changes in survival over time were assessed by multivariate excess hazard model of mortality. In total, 68,312 HNC patients were included in this analysis. We observed an overall improvement in 5-year NS for HNC patients in Japan. However, survival varied among subsites of HNC, with some, such as naso-, oro- and hypopharyngeal cancers, showing significant improvement in both 5- and 10-year NS, whereas others such as laryngeal cancer showed only a slight improvement in 5-year NS and no significant change in 10-year NS after adjustment for age, sex and stage. In conclusion, the study provides insights into changing HNC survival by site at the population level in Japan. Although advances in diagnostic techniques and treatment modalities have improved survival, these improvements are not shared equally among subsites.

Cancer incidence and type of treatment hospital among children, adolescents, and young adults in Japan, 2016-2018.

Cancer in children, adolescents, and young adults (AYAs) although rare, is the leading disease-specific cause of death in Japan. This study aims to investigate cancer incidence and type of treatment hospital among children and AYAs in Japan. Cancer incidence data (2016-2018) for those aged 0-39 years were obtained from the Japanese population-based National Cancer Registry. Cancer types were classified according to the 2017 update of the International Classification of Childhood Cancer (Third Edition), and AYA Site Recode 2020 Revision. Cases were also categorized into three groups: those treated at core hospitals for pediatric cancer treatment (pediatric cancer hospitals [PCHs]), those treated at designated cancer care hospitals, and those treated at nondesignated hospitals. The age-standardized incidence rate was 166.6 (per million-person years) for children (age 0-14 years) and 579.0 for AYAs (age 15-39 years) (including all cancers and benign or uncertain-behavior central nervous system [CNS] tumors). The type of cancer varied with age: hematological malignancies, blastomas, and CNS tumors were common in children under 10 years, malignant bone tumors and soft tissue sarcomas were relatively common in teenagers, and in young adults over 20 years, carcinomas in thyroid, testis, gastrointestinal, female cervix, and breast were common. The proportion of cases treated at PCHs ranged from 20% to 30% for children, 10% or less for AYAs, and differed according to age group and cancer type. Based on this information, the optimal system of cancer care should be discussed.

Fifteen-year survival and conditional survival of women with breast cancer in Osaka, Japan: A population-based study.

BACKGROUND: In recent years, the survival of patients with breast cancer has improved. However, few published studies have a longer than 10-year follow-up. Conditional relative survival (CRS), which is relative survival (RS) of patients who have survived beyond a certain period after diagnosis, is useful for assessing excess mortality among long-term survivors compared with the general population. METHODS: This was a retrospective observational cohort study. Population-based cancer registry data in Osaka, Japan were used to determine 15-year RS and 5-year CRS of women with breast cancer diagnosed between 2001 and 2002 and followed up for at least 15 years. Fifteen-year RS and age-standardized RS (ASR) were calculated by Ederer II and cohort methods. Five-year CRS according to age group and extent of disease (localized, regional, and distant) was estimated for every year from diagnosis to 10 years. RESULTS: In the cohort of 4006 patients, the ASR declined progressively, the 5-year ASR being 85.8%, 10-year ASR 77.3%, and 15-year ASR 71.6%. The overall 5-year CRS exceeded 90% at 5 years after diagnosis, reflecting a small excess mortality compared with the general population. The 5-year CRS of patients with regional and distant disease did not reach 90% within 10 years of follow-up (89.4% for regional and 72.9% for distant disease 10 years after diagnosis), indicating that these patients had substantial excess mortality. CONCLUSION: Long-term survival data can help cancer survivors plan their lives and receive better medical care and support.

Survival in non-small cell lung cancer patients with versus without prior cancer.

Clinical trials on cancer treatments frequently exclude patients with prior cancer, but more evidence is needed to understand their possible effects on outcomes. This study analyzed the prognostic impact of prior cancer in newly diagnosed non-small cell lung cancer (NSCLC) patients while accounting for various patient and cancer characteristics. Using population-based cancer registry data linked with administrative claims data, this retrospective cohort study examined patients aged 15-84 years diagnosed with NSCLC between 2010 and 2015 in Japan. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality in patients with versus without prior cancer. The analysis was stratified according to NSCLC stage and diagnostic time intervals between prior cancers and the index NSCLC. We analyzed 9103 patients (prior cancer: 1416 [15.6%]; no prior cancer: 7687 [84.4%]). Overall, prior cancer had a non-significant mortality HR of 1.07 (95% CI: 0.97-1.17). Furthermore, prior cancer had a significantly higher mortality hazard for diagnostic time intervals of 3 years (HR: 1.23, 95% CI: 1.06-1.43) and 5 years (1.18, 1.04-1.33), but not for longer intervals. However, prior cancer in patients with more advanced NSCLC did not show a higher mortality risk for any diagnostic time interval. Smoking-related prior cancers and prior cancers with poorer prognosis were associated with poorer survival. NSCLC patients with prior cancer do not have an invariably higher risk of mortality, and should be considered for inclusion in clinical trials depending on their cancer stage.

Patterns of staging, treatment, and mortality in gastric, colorectal, and lung cancer among older adults with and without preexisting dementia: a Japanese multicentre cohort study.

BACKGROUND: Little is known about dementia's impact on patterns of diagnosis, treatment, and outcomes in cancer patients. This study aimed to elucidate the differences in cancer staging, treatment, and mortality in older cancer patients with and without preexisting dementia. METHODS: Using cancer registry data and administrative data from 30 hospitals in Japan, this multicentre retrospective cohort study examined patients aged 65-99 years who were newly diagnosed with gastric, colorectal, or lung cancer in 2014-2015. Dementia status (none, mild, and moderate-to-severe) at the time of cancer diagnosis was extracted from clinical summaries in administrative data, and set as the exposure of interest. We constructed multivariable logistic regression models to analyse cancer staging and treatment, and multivariable Cox regression models to analyse three-year survival. RESULTS: Among gastric (n = 6016), colorectal (n = 7257), and lung (n = 4502) cancer patients, 5.1%, 5.8%, and 6.4% had dementia, respectively. Patients with dementia were more likely to receive unstaged and advanced-stage cancer diagnoses; less likely to undergo tumour resection for stage I, II, and III gastric cancer and for stage I and II lung cancer; less likely to receive pharmacotherapy for stage III and IV lung cancer; more likely to undergo tumour resection for all-stage colorectal cancer; and more likely to die within three years of cancer diagnosis. The effects of moderate-to-severe dementia were greater than those of mild dementia, with the exception of tumour resection for colorectal cancer. CONCLUSION: Older cancer patients with preexisting dementia are less likely to receive standard cancer treatment and more likely to experience poorer outcomes. Clinicians should be aware of these risks, and would benefit from standardised guidelines to aid their decision-making in diagnosing and treating these patients.

Socioeconomic disparities in cancer survival: Relation to stage at diagnosis, treatment, and centralization of patients to accredited hospitals, 2005-2014, Japan.

BACKGROUND: Cancer survival varies by socioeconomic status in Japan. We examined the extent to which survival disparities are explained by factors relevant to cancer control measures (promoting early-stage detection, standardizing treatment, and centralizing patients to government-accredited cancer hospitals [ACHs]). METHODS: From the Osaka Cancer Registry, patients diagnosed with solid malignant tumors during 2005-2014 and aged 15-84 years (N = 376,077) were classified into quartiles using the Area Deprivation Index (ADI). Trends in inequalities were assessed for potentially associated factors: early-stage detection, treatment modality, and utilization of ACH (for first contact/diagnosis/treatment). 3-year all-cause survival was computed by the ADI quartile. Multivariable Cox regression models were used to assess survival disparities and their trends through a series of adjustment for the potentially associated factors. RESULTS: During 2005-2014, the most deprived ADI quartile had lower rates than the least deprived quartile for early-stage detection (42.6% vs. 48.7%); receipt of surgery (58.1% vs. 64.1%); and utilization of ACH (83.5% vs. 88.4%). While rate differences decreased for receipt of surgery and utilization of ACH (Annual Percent Change = -3.2 and - 11.9, respectively) over time, it remained unchanged for early-stage detection. During 2012-2014, the most deprived ADI quartile had lower 3-year survival than the least deprived (59.0% vs. 69.4%) and higher mortality (Hazard Ratio [HR] = 1.32, adjusted for case-mix): this attenuated with additional adjustment for stage at diagnosis (HR = 1.23); treatment modality (HR = 1.20); and utilization of ACH (HR = 1.19) CONCLUSIONS: Despite improvements in equalizing access to quality cancer care during 2005-2014, survival disparities remained. Interventions to reduce inequalities in early-stage detection could ameliorate such gaps.

Minimum surgical volume to ensure 5-year survival probability for six cancer sites in Japan.

BACKGROUND: In Japan, the government designates hospitals specialized in cancer care, requiring them to perform 400 surgeries annually without requiring surgical volume per cancer site. This study aimed to estimate the site-specific minimum surgical volume per year based on its associations with 5-year survival probability. METHODS: The data of 64,402 patients who had undergone surgery for six types of cancers (including esophageal, stomach, colorectal, pancreatic, lung, and breast cancers) at designated cancer care hospitals in Osaka between 2007 and 2011 were analyzed. The hospitals were categorized by the average annual surgical volume per cancer type (e.g., 0-4, 5-9, 10-14…). We estimated the adjusted 5-year survival probability per surgical volume category using multivariable Cox proportional hazard regression. Furthermore, we identified inflection points for the trend of adjusted survival probability per increase of five surgical volumes using the joinpoint regression model and considered them as the suggested minimum surgical volume. RESULTS: The estimated minimum surgical volumes were 35-39, 20-25, 25-29, 10-14, 10-14, and 25-29 for esophageal, stomach, colorectal, pancreatic, lung, and breast cancers, respectively. The percentage change in the adjusted 5-year survival probability per increase of five surgical volumes before and after the suggested surgical volume were +2.23 and +0.39 for the esophagus, +9.68 and +0.34 for the stomach, +8.11 and +0.05 for the colorectum, +3.82 and +0.87 for the pancreas, +9.46 and +0.23 for the lung, and +1.27 and +0.03 for the breast. CONCLUSIONS: The suggested surgical volume based on the association with survival probability varies with cancer sites, some of which are close to the existing surgical volume standards used in Japan. These evidence-based minimum surgical volumes may help improve the quality of cancer surgeries.

Impact of coexisting diabetes on survival and risk of developing second primary cancer in diabetes patients receiving drug therapy: A multicenter retrospective cohort study of patients with cancer in Japan.

AIMS/INTRODUCTION: We investigated the association between coexisting diabetes at the time of cancer diagnosis, and the overall survival and incidence of second primary cancer in patients with cancer and receiving drug therapy for diabetes. MATERIALS AND METHODS: We used cancer registry and administrative data of patients diagnosed with cancer at designated cancer care hospitals in Osaka Prefecture between 2010 and 2015. The presence of diabetes was identified from the prescription records of antidiabetic drugs in Diagnosis Procedure Combination System data. After adjusting for patient characteristics, we compared overall survival between patients with cancer with coexisting diabetes and those without coexisting diabetes using the Cox proportional hazards model. In addition, the impact of coexisting diabetes on the risk of developing second primary cancer was evaluated using a competing risk analysis. RESULTS: Of the 131,701 patients with cancer included in the analysis, 6,135 (4.7%) had coexisting diabetes. The 5-year survival rates for patients with and without coexisting diabetes were 56.2% (95% confidence interval 54.8-57.6) and 72.7% (95% confidence interval 72.4-73.0), respectively. Coexisting diabetes was associated with a higher risk of developing second primary cancer (subdistribution hazard ratio 1.23; 95% confidence interval 1.08-1.41). In site-specific analysis, coexisting diabetes was associated with an increased risk for the development of second primary cancer of multiple myeloma, and cancer of the uterus, pancreas and liver. CONCLUSIONS: Coexisting diabetes was associated with a higher mortality and risk of developing second primary cancer in Japanese patients with cancer and on drug therapy for diabetes.

Incidence of second primary cancers among survivors of childhood cancer: A population-based study, Osaka, Japan, 1975-2015.

Second primary cancer (SPC) is one of the most life-threatening late effects of childhood cancers. We investigated the incidence and survival outcomes of SPC in childhood cancer patients in Japan. Data were obtained from the population-based Osaka Cancer Registry. Individuals diagnosed with cancer at age 0-14 years during 1975-2014 and survived 2 months or longer were followed through December 2015. The risk of developing SPC was assessed with standardized incidence ratio (SIR), excess absolute risk (EAR, per 100,000 person-years), and cumulative incidence. Multivariable Poisson regression analysis was carried out to assess relative risks of SPC by treatment method. Survival analysis was undertaken using the Kaplan-Meier method. Of 7229 childhood cancer survivors, 101 (1.4%) developed SPC after a median of 11.6 years. Overall SIR was 5.0, which corresponded with 84.3 EAR. The cumulative incidence was 0.9%, 2.1%, and 3.4% at 10, 20, and 30 years, respectively. Among all SPCs, the type that contributed most to the overall burden was cancers in the central nervous system (EAR = 28.0) followed by digestive system (EAR = 15.1), thyroid (EAR = 8.3), and bones and joints (EAR = 7.8); median latency ranged from 2.0 years (lymphomas) to 26.6 years (skin cancers). Patients treated with radiotherapy alone were at a 2.58-fold increased risk of developing SPC compared to those who received neither chemotherapy nor radiotherapy. Among patients who developed SPCs, 5-year and 10-year survival probabilities after SPC diagnosis were 61.7% and 52.0%, respectively. Risk-based long-term follow-up planning is essential to inform survivorship care and help reduce the burden of SPCs in childhood cancer survivors.